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[ CAS No. 1352226-88-0 ] {[proInfo.proName]}

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Chemical Structure| 1352226-88-0
Chemical Structure| 1352226-88-0
Structure of 1352226-88-0 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1352226-88-0 ]

CAS No. :1352226-88-0 MDL No. :MFCD28952790
Formula : C20H24N6O2S Boiling Point : -
Linear Structure Formula :- InChI Key :OHUHVTCQTUDPIJ-JYCIKRDWSA-N
M.W : 412.51 Pubchem ID :54761306
Synonyms :
AZD6738

Calculated chemistry of [ 1352226-88-0 ]

Physicochemical Properties

Num. heavy atoms : 29
Num. arom. heavy atoms : 15
Fraction Csp3 : 0.45
Num. rotatable bonds : 4
Num. H-bond acceptors : 6.0
Num. H-bond donors : 2.0
Molar Refractivity : 116.59
TPSA : 116.23 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -6.89 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.32
Log Po/w (XLOGP3) : 2.72
Log Po/w (WLOGP) : 3.26
Log Po/w (MLOGP) : 1.3
Log Po/w (SILICOS-IT) : 2.63
Consensus Log Po/w : 2.45

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -4.23
Solubility : 0.0243 mg/ml ; 0.0000589 mol/l
Class : Moderately soluble
Log S (Ali) : -4.81
Solubility : 0.00632 mg/ml ; 0.0000153 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -5.76
Solubility : 0.000712 mg/ml ; 0.00000173 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 4.67

Safety of [ 1352226-88-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1352226-88-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1352226-88-0 ]

[ 1352226-88-0 ] Synthesis Path-Downstream   1~50

  • 1
  • [ 55052-24-9 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 1.2: pH 7 2.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 3.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 5.1: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 1.2: pH 7 2.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 3.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 5.1: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 6.1: triethylamine / ethanol; 2-Methylpentane; methanol
  • 2
  • [ 55052-24-9 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 1.2: pH 7 2.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 3.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 4.2: 18 h / 50 °C
Multi-step reaction with 3 steps 1.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 1.2: pH 7 2.1: sodium hydride / tetrahydrofuran / 0.17 h / 20 °C / Inert atmosphere 2.2: 0.33 h / -78 °C 3.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 5 steps 1.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 1.2: pH 7 2.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 3.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 5.1: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
  • 3
  • [ 271-63-6 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: n-heptane; 1,2-dimethoxyethane / 19 h / 20 °C / Inert atmosphere 2.1: potassium carbonate / water / 2 h / 20 °C / pH 10 3.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 3.2: pH 7 4.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 5.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 7.1: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: n-heptane; 1,2-dimethoxyethane / 19 h / 20 °C / Inert atmosphere 2.1: potassium carbonate / water / 2 h / 20 °C / pH 10 3.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 3.2: pH 7 4.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 5.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 7.1: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 8.1: triethylamine / ethanol; 2-Methylpentane; methanol
  • 4
  • [ 271-63-6 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: n-heptane; 1,2-dimethoxyethane / 19 h / 20 °C / Inert atmosphere 2.1: potassium carbonate / water / 2 h / 20 °C / pH 10 3.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 3.2: pH 7 4.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 5.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1.1: n-heptane; 1,2-dimethoxyethane / 19 h / 20 °C / Inert atmosphere 2.1: potassium carbonate / water / 2 h / 20 °C / pH 10 3.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 3.2: pH 7 4.1: sodium hydride / tetrahydrofuran / 0.17 h / 20 °C / Inert atmosphere 4.2: 0.33 h / -78 °C 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1.1: n-heptane; 1,2-dimethoxyethane / 19 h / 20 °C / Inert atmosphere 2.1: potassium carbonate / water / 2 h / 20 °C / pH 10 3.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 3.2: pH 7 4.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 5.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7.1: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
  • 5
  • [ 6299-85-0 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 10: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 10: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 11 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 11: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 11 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 11: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C

  • 6
  • [ 6299-85-0 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 10 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7.1: triethylamine / ethanol; 2-Methylpentane 8.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 9.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 10.2: 18 h / 50 °C
Multi-step reaction with 10 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7.1: triethylamine / ethanol; 2-Methylpentane 8.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 9.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 10.2: 18 h / 50 °C
Multi-step reaction with 10 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7.1: triethylamine / ethanol; 2-Methylpentane 8.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 9.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 10.2: 18 h / 50 °C
Multi-step reaction with 10 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7.1: triethylamine / ethanol; 2-Methylpentane 8.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 9.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 10.2: 18 h / 50 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: triethylamine / ethanol; 2-Methylpentane 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: triethylamine / ethanol; 2-Methylpentane 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: triethylamine / ethanol; 2-Methylpentane 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: triethylamine / ethanol; 2-Methylpentane 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: triethylamine / ethanol; 2-Methylpentane 8: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 9: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: triethylamine / ethanol; 2-Methylpentane 8: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 9: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: triethylamine / ethanol; 2-Methylpentane 8: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 9: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: triethylamine / ethanol; 2-Methylpentane 8: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 9: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 10 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 11 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: triethylamine / ethanol; 2-Methylpentane 8: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 9: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 11: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 11 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: triethylamine / ethanol; 2-Methylpentane 8: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 9: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 11: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 11 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: triethylamine / ethanol; 2-Methylpentane 8: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 9: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 11: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 11 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7: triethylamine / ethanol; 2-Methylpentane 8: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 9: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 10: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 11: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: triethylamine / ethanol; 2-Methylpentane 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: triethylamine / ethanol; 2-Methylpentane 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: triethylamine / ethanol; 2-Methylpentane 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: triethylamine / ethanol; 2-Methylpentane 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 1.58 h / 25 °C 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: triethylamine / dichloromethane / 18 h / 20 °C 2.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5.1: N,N-dimethyl-formamide / 1 h / 20 °C 6.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 4: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 18 h / 20 °C 2: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 3: triethylamine / dichloromethane / 1.58 h / 25 °C 4: lithium iodide / 1,4-dioxane / 1 h / 107 °C 5: N,N-dimethyl-formamide / 1 h / 20 °C 6: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere

Reference: [1]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[2]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[3]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[4]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[5]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[6]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[7]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[8]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[9]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[10]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[11]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[12]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[13]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[14]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[15]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[16]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[17]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[18]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[19]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[20]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[21]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[22]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[23]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[24]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[25]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[26]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[27]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[28]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[29]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[30]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[31]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[32]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[33]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[34]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[35]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[36]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[37]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[38]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[39]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[40]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[41]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[42]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[43]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[44]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[45]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[46]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[47]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[48]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[49]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[50]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
  • 7
  • [ 348640-06-2 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 2: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 4: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 5 steps 1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 2: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 4: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 5: triethylamine / ethanol; 2-Methylpentane; methanol
  • 8
  • [ 348640-06-2 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sodium hydroxide / tetrabutylammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 2.1: anhydrous potassium acetate / palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 3.1: anhydrous sodium carbonate / [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,2-dimethoxyethane; water monomer / 4 h / 90 °C / Inert atmosphere 3.2: 18 h / 50 °C
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.17 h / 20 °C / Inert atmosphere 1.2: 0.33 h / -78 °C 2.1: anhydrous sodium carbonate / [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: sodium hydroxide / tetrabutylammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 2: anhydrous potassium acetate / palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 3: anhydrous sodium carbonate / [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 1,2-dimethoxyethane; water monomer / 2 h / 90 °C / Inert atmosphere 4: sodium hydroxide / 1,2-dimethoxyethane; water monomer / 96 h / 20 °C
Multi-step reaction with 2 steps 1.1: sodium hydride / mineral oil; tetrahydrofuran / 0.75 h / 5 - 20 °C / Inert atmosphere 1.2: 0.17 h / -74 °C / Inert atmosphere 1.3: 0.75 h / Inert atmosphere 2.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); anhydrous sodium carbonate / water monomer; 1,2-dimethoxyethane / 2 h / 90 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: Isopropyl acetate; anhydrous potassium acetate; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 22 h / 85 - 90 °C / Inert atmosphere; Large scale; Enzymatic reaction 2: potassium carbonate; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / ethanol; water monomer / 4 h / 80 °C / Inert atmosphere; Large scale; Enzymatic reaction
Multi-step reaction with 2 steps 1.1: 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; anhydrous potassium acetate; palladium diacetate / tetrahydrofuran / 22 h / 90 °C / Inert atmosphere; Glovebox 2.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic / water monomer; ethanol / 17 h / 75 °C / Inert atmosphere; Large scale 2.2: 8 h / 60 °C / Large scale
Multi-step reaction with 2 steps 1.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); anhydrous potassium acetate / Isopropyl acetate / 22 h / 85 - 90 °C / Inert atmosphere; Large scale 1.2: mercapto silica / 8 h / 50 °C / Large scale 2.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); tripotassium phosphate tribasic / water monomer; ethanol / 17 h / 75 °C / Inert atmosphere; Large scale 2.2: 8 h / 60 °C / Large scale
Multi-step reaction with 8 steps 1.1: potassium-t-butoxide / N,N-dimethyl acetamide / 0.25 h / 0 °C / Inert atmosphere 1.2: 13 h / 0 - 20 °C / Inert atmosphere 2.1: anhydrous potassium acetate; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / 1,4-dioxane / 6 h / Inert atmosphere 3.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate / water monomer; toluene / 0.58 h / 90 °C / Inert atmosphere 4.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 7 h / -78 °C / Inert atmosphere 5.1: trifluoroacetic acid / dichloromethane / 3.5 h / 20 °C / Inert atmosphere 5.2: 72 h / 80 °C 6.1: sodium hydride; benzo-15-crown-5 / 1,4-dioxane / 0.33 h / 20 °C / Inert atmosphere 6.2: 18 h / 50 °C / Inert atmosphere 7.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 8.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 8.2: 4 h / 20 °C
Multi-step reaction with 8 steps 1.1: potassium-t-butoxide / N,N-dimethyl acetamide / 0.25 h / 0 °C / Inert atmosphere 1.2: 13 h / 0 - 20 °C / Inert atmosphere 2.1: anhydrous potassium acetate; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / 1,4-dioxane / 6 h / Inert atmosphere 3.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate / toluene; water monomer / 0.58 h / 90 °C / Inert atmosphere 4.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 7 h / -78 °C / Inert atmosphere 5.1: trifluoroacetic acid / dichloromethane / 3.5 h / 20 °C / Inert atmosphere 5.2: 72 h / 80 °C 6.1: sodium hydride; benzo-15-crown-5 / 1,4-dioxane / 0.33 h / 20 °C / Inert atmosphere 6.2: 18 h / 50 °C / Inert atmosphere 7.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 8.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 8.2: 4 h / 20 °C

Reference: [1]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[2]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[3]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[4]Foote, Kevin M.; Nissink, J. Willem M.; McGuire, Thomas; Turner, Paul; Guichard, Sylvie; Yates, James W. T.; Lau, Alan; Blades, Kevin; Heathcote, Dan; Odedra, Rajesh; Wilkinson, Gary; Wilson, Zena; Wood, Christine M.; Jewsbury, Philip J. [Journal of Medicinal Chemistry, 2018, vol. 61, # 22, p. 9889 - 9907]
[5]Current Patent Assignee: ASTRAZENECA PLC - WO2020/127208, 2020, A2
[6]Graham, Mark A.; Askey, Hannah; Campbell, Andrew D.; Chan, Lai; Cooper, Katie G.; Cui, Zhaoshan; Dalgleish, Andrew; Dave, David; Ensor, Gareth; Galan Espinosa, Maria Rita; Hamilton, Peter; Heffernan, Claire; Jackson, Lucinda V.; Jing, Dajiang; Jones, Martin F.; Liu, Pengpeng; Mulholland, Keith R.; Pervez, Mohammed; Popadynec, Michael; Randles, Emma; Tomasi, Simone; Wang, Shenghua [Organic Process Research and Development, 2021, vol. 25, # 1, p. 43 - 56]
[7]Graham, Mark A.; Askey, Hannah; Campbell, Andrew D.; Chan, Lai; Cooper, Katie G.; Cui, Zhaoshan; Dalgleish, Andrew; Dave, David; Ensor, Gareth; Galan Espinosa, Maria Rita; Hamilton, Peter; Heffernan, Claire; Jackson, Lucinda V.; Jing, Dajiang; Jones, Martin F.; Liu, Pengpeng; Mulholland, Keith R.; Pervez, Mohammed; Popadynec, Michael; Randles, Emma; Tomasi, Simone; Wang, Shenghua [Organic Process Research and Development, 2021, vol. 25, # 1, p. 43 - 56]
[8]Bikowitz, Melissa J.; Chen, Jiandong; Chen, Lihong; Grassie, Dylan; Karim, Rezaul Md; Lopchuk, Justin M.; Lu, Junhao; Shultz, Zachary P.; Yang, Leixiang; Schönbrunn, Ernst [Journal of Medicinal Chemistry, 2022, vol. 65, # 5, p. 4182 - 4200]
[9]Bikowitz, Melissa J.; Chen, Jiandong; Chen, Lihong; Grassie, Dylan; Karim, Rezaul Md; Lopchuk, Justin M.; Lu, Junhao; Shultz, Zachary P.; Yang, Leixiang; Schönbrunn, Ernst [Journal of Medicinal Chemistry, 2022, vol. 65, # 5, p. 4182 - 4200]
  • 9
  • [ 348640-07-3 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
  • 10
  • [ 348640-07-3 ]
  • [ 1352226-88-0 ]
  • 11
  • [ 916176-50-6 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 2: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 3 steps 1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 2: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 3: triethylamine / ethanol; 2-Methylpentane; methanol
  • 12
  • [ 916176-50-6 ]
  • [ 1352282-87-1 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
71% Stage #1: 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridine; (3R)-4-(2-chloro-6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine With sodium carbonate In 1,2-dimethoxyethane; water at 90℃; for 4h; Inert atmosphere; Stage #2: With sodium hydroxide In 1,2-dimethoxyethane; water at 50℃; for 18h; 2.01; 2.02 Example 2.02 can also be prepared as follows:Dichlorobis(triphenylphosphine)palladium(II) (2.59 mg, 3.69 μmol) was added in one portion to (3R)-4-(2-chloro-6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (63 mg, 0.15 mmol), 2M aqueous Na2CO3 solution (0.089 ml, 0.18 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (58.8 mg, 0.15 mmol) in DME:water 4:1 (5 ml) at RT. The reaction mixture was stirred at 90° C. for 4 hours. Sodium hydroxide, 2M aqueous solution (0.131 ml, 0.26 mmol) was added and the mixture was heated at 50° C. for 18 hours. The reaction mixture was acidified with 2M HCl to pH7. The reaction mixture was filtered and then purified by preparative HPLC using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Pure fractions were evaporated and the residue triturated with isohexane and Et2O to give a solid which was collected by filtration and dried under vacuum to afford the title compound (44.0 mg, 71%); 1H NMR (400 MHz, DMSO-d6) 1.29 (3H, d), 1.40-1.61 (3H, m), 1.70-1.81 (1H, m), 3.10 (3H, d), 3.53 (1H, dd), 3.68 (1H, dd), 3.77-3.87 (2H, m), 4.02 (1H, dd), 4.19 (1H, d), 4.58 (1H, s), 7.01 (1H, d), 7.23 (1H, dd), 7.55-7.61 (1H, m), 7.95 (1H, d), 8.34 (1H, d), 11.75 (1H, s).; m/z: (ES+) MH+, 413.19. Chiral HPLC: (HP1100 System 4, 5 μm Chiralcel OJ-H (250 mm×4.6 mm) column eluting with iso-Hexane/EtOH/MeOH/TEA 50/25/25/0.1) Rf, 9.023 88.0%, 15.796 12.0%.
Multi-step reaction with 2 steps 1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 2: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
  • 13
  • 1H-pyrrolo[2,3-b]pyridine 1-oxide meta-chlorobenzoic acid salt [ No CAS ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: potassium carbonate / water / 2 h / 20 °C / pH 10 2.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 2.2: pH 7 3.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 4.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 6.1: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: potassium carbonate / water / 2 h / 20 °C / pH 10 2.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 2.2: pH 7 3.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 4.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 6.1: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 7.1: triethylamine / ethanol; 2-Methylpentane; methanol
  • 14
  • 1H-pyrrolo[2,3-b]pyridine 1-oxide meta-chlorobenzoic acid salt [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: potassium carbonate / water / 2 h / 20 °C / pH 10 2.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 2.2: pH 7 3.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 4.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 5.2: 18 h / 50 °C
Multi-step reaction with 4 steps 1.1: potassium carbonate / water / 2 h / 20 °C / pH 10 2.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 2.2: pH 7 3.1: sodium hydride / tetrahydrofuran / 0.17 h / 20 °C / Inert atmosphere 3.2: 0.33 h / -78 °C 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1.1: potassium carbonate / water / 2 h / 20 °C / pH 10 2.1: tetramethylammonium bromide; Methanesulfonic anhydride / N,N-dimethyl-formamide / 24.5 h / 0 - 20 °C / Inert atmosphere 2.2: pH 7 3.1: sodium hydroxide / tetra(n-butyl)ammonium hydrogensulfate / dichloromethane / 1 h / 20 °C 4.1: potassium acetate / (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide / 24 h / 90 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 6.1: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
  • 15
  • [ 1233339-69-9 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 10 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 10: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 10 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 10: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 9 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 9: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 9 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 9: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 9 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C

  • 16
  • [ 1233339-69-9 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 10 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: triethylamine / ethanol; 2-Methylpentane 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: triethylamine / ethanol; 2-Methylpentane 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: triethylamine / ethanol; 2-Methylpentane 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 10 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: triethylamine / ethanol; 2-Methylpentane 7: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 10: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: triethylamine / ethanol; 2-Methylpentane 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: triethylamine / ethanol; 2-Methylpentane 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: triethylamine / ethanol; 2-Methylpentane 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: triethylamine / ethanol; 2-Methylpentane 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: triethylamine / ethanol; 2-Methylpentane 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: triethylamine / ethanol; 2-Methylpentane 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: triethylamine / ethanol; 2-Methylpentane 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: triethylamine / ethanol; 2-Methylpentane 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 9 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: triethylamine / ethanol; 2-Methylpentane 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 1.58 h / 25 °C 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: triethylamine / ethanol; 2-Methylpentane 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: triethylamine / ethanol; 2-Methylpentane 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1.1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4.1: N,N-dimethyl-formamide / 1 h / 20 °C 5.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 6.1: triethylamine / ethanol; 2-Methylpentane 7.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 8.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 9.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 9.2: 18 h / 50 °C
Multi-step reaction with 9 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 9 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 1.58 h / 25 °C 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 9 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 9 steps 1: lithium borohydride / tetrahydrofuran / 18.83 h / 0 - 20 °C / Inert atmosphere 2: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 3: lithium iodide / 1,4-dioxane / 1 h / 107 °C 4: N,N-dimethyl-formamide / 1 h / 20 °C 5: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 6: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 9: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C

Reference: [1]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[2]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[3]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[4]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[5]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[6]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[7]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[8]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[9]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[10]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[11]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[12]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[13]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[14]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[15]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[16]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[17]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[18]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[19]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[20]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[21]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[22]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[23]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[24]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[25]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[26]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[27]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[28]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[29]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[30]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[31]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[32]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[33]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[34]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[35]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[36]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[37]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[38]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[39]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[40]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[41]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[42]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[43]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[44]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[45]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[46]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[47]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[48]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[49]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[50]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
  • 17
  • [ 1233339-70-2 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 8: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 8: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 9: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 9 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 9: triethylamine / ethanol; 2-Methylpentane; methanol

  • 18
  • [ 1233339-70-2 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4.1: triethylamine / ethanol; 2-Methylpentane 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4.1: triethylamine / ethanol; 2-Methylpentane 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4.1: triethylamine / ethanol; 2-Methylpentane 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4.1: triethylamine / ethanol; 2-Methylpentane 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: triethylamine / ethanol; 2-Methylpentane 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 1.58 h / 25 °C 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: triethylamine / ethanol; 2-Methylpentane 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: triethylamine / ethanol; 2-Methylpentane 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1.1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3.1: N,N-dimethyl-formamide / 1 h / 20 °C 4.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 5.1: triethylamine / ethanol; 2-Methylpentane 6.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 7.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 8.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 8.2: 18 h / 50 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 1.58 h / 25 °C 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: lithium iodide / 1,4-dioxane / 1 h / 107 °C 3: N,N-dimethyl-formamide / 1 h / 20 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: triethylamine / dichloromethane / 2.25 h / 5 - 15 °C / Inert atmosphere 2: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C

Reference: [1]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[2]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[3]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[4]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[5]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[6]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[7]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[8]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[9]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[10]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[11]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[12]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[13]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[14]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[15]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[16]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[17]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[18]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[19]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[20]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[21]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[22]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[23]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[24]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[25]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[26]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[27]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[28]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[29]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[30]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[31]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[32]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[33]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[34]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[35]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[36]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[37]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[38]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[39]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[40]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[41]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[42]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[43]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[44]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[45]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[46]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[47]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[48]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[49]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[50]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
  • 19
  • [ 1233339-71-3 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 6 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 7 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 7: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 8 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 8: triethylamine / ethanol; 2-Methylpentane; methanol

  • 20
  • [ 1233339-71-3 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2.1: N,N-dimethyl-formamide / 1 h / 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 4.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 5.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 5.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 5.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 5 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 5 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2.1: N,N-dimethyl-formamide / 1 h / 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2.1: N,N-dimethyl-formamide / 1 h / 20 °C 3.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3.1: triethylamine / ethanol; 2-Methylpentane 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3.1: triethylamine / ethanol; 2-Methylpentane 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 6 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 6 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 6 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: triethylamine / ethanol; 2-Methylpentane 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: triethylamine / ethanol; 2-Methylpentane 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2.1: N,N-dimethyl-formamide / 1 h / 20 °C 3.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4.1: triethylamine / ethanol; 2-Methylpentane 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1.1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2.1: N,N-dimethyl-formamide / 1 h / 20 °C 3.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4.1: triethylamine / ethanol; 2-Methylpentane 5.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 7.2: 18 h / 50 °C
Multi-step reaction with 7 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: triethylamine / ethanol; 2-Methylpentane 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: sodium iodide / acetonitrile / 16.08 h / 18 - 30 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: triethylamine / ethanol; 2-Methylpentane 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 8 steps 1: lithium iodide / 1,4-dioxane / 1 h / 107 °C 2: N,N-dimethyl-formamide / 1 h / 20 °C 3: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 4: triethylamine / ethanol; 2-Methylpentane 5: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 6: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 7: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 8: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide; 2-methyltetrahydrofuran / 60 °C 2: (2R)-2-amino-3,3-dimethylbutan-1-ol; bis(acetylacetonato) oxovanadium(IV); dihydrogen peroxide; 3-(tert-butyl)-5-nitrosalicylaldehyde / dichloromethane / 24 h / 20 °C 3: [bis(acetoxy)iodo]benzene; magnesium oxide; dirhodium tetraacetate / 24 h / 20 °C 4: sodium hydroxide / 2-methyltetrahydrofuran; water / 24 h / 20 °C 5: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; ethanol / 0.33 h / 110 °C

Reference: [1]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[2]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[3]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[4]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[5]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[6]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[7]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[8]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[9]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[10]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[11]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[12]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[13]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[14]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[15]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[16]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[17]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[18]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[19]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[20]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[21]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[22]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[23]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[24]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[25]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[26]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[27]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[28]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[29]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[30]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[31]Current Patent Assignee: JIANGSU JICUI MOLECULE ENGINEERING RES INSTITUTE - CN111646985, 2020, A
  • 21
  • [ 1233339-72-4 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 7 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 7: triethylamine / ethanol; 2-Methylpentane; methanol
  • 22
  • [ 1233339-72-4 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: N,N-dimethyl-formamide / 1 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 5.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1.1: N,N-dimethyl-formamide / 1 h / 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 4.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 5.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1.1: N,N-dimethyl-formamide / 1 h / 20 °C 2.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 5.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1.1: N,N-dimethyl-formamide / 1 h / 20 °C 2.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3.1: triethylamine / ethanol; 2-Methylpentane 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1.1: N,N-dimethyl-formamide / 1 h / 20 °C 2.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3.1: triethylamine / ethanol; 2-Methylpentane 4.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 6.2: 18 h / 50 °C
Multi-step reaction with 6 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 6 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 6 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 6 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: triethylamine / ethanol; 2-Methylpentane 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: triethylamine / ethanol; 2-Methylpentane 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 7 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: triethylamine / ethanol; 2-Methylpentane 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 7 steps 1: N,N-dimethyl-formamide / 1 h / 20 °C 2: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 3: triethylamine / ethanol; 2-Methylpentane 4: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 5: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 6: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 7: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 5 steps 1: N,N-dimethyl-formamide / 1 h / 25 °C 2: sodium periodate / water; methanol; ethyl acetate / 16 h / 20 °C / Inert atmosphere 3: dirhodium tetraacetate; [bis(acetoxy)iodo]benzene; magnesium oxide / dichloromethane / 16 h / 20 °C 4: tetraoctyl ammonium bromide; sodium hydroxide / 2-methyltetrahydrofuran / 4.17 h / 20 °C / Inert atmosphere 5: bis-triphenylphosphine-palladium(II) chloride; sodium carbonate / water; 1,2-dimethoxyethane / 2 h / 90 °C / Inert atmosphere

Reference: [1]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[2]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[3]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[4]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[5]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[6]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[7]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[8]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[9]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[10]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[11]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[12]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[13]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[14]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[15]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[16]Foote, Kevin M.; Nissink, J. Willem M.; McGuire, Thomas; Turner, Paul; Guichard, Sylvie; Yates, James W. T.; Lau, Alan; Blades, Kevin; Heathcote, Dan; Odedra, Rajesh; Wilkinson, Gary; Wilson, Zena; Wood, Christine M.; Jewsbury, Philip J. [Journal of Medicinal Chemistry, 2018, vol. 61, # 22, p. 9889 - 9907]
  • 23
  • [ 1246761-84-1 ]
  • [ 1352282-87-1 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
46% With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; at 85℃; for 6h;Inert atmosphere; Example 2.02 can also be prepared as follows:Dichlorobis(triphenylphosphine)palladium(II) (0.061 g, 0.09 mmol) was added to (3R)-4-(2-chloro-6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)pyrimidin-4-yl)-3-methylmorpholine (1.15 g, 3.48 mmol), 2M sodium carbonate solution (6.95 ml, 13.90 mmol) and <strong>[1246761-84-1]1H-pyrrolo[2,3-b]pyridin-4-ylboronic acid</strong> (1.877 g, 3.48 mmol) under nitrogen. The resulting solution was stirred at 85 C. for 6 hours. The reaction mixture was diluted with EtOAc (200 ml), and washed sequentially with water (200 ml) and saturated brine (100 ml). The organic layer was dried over MgSO4, filtered and then evaporated onto silica gel (10 g). The resulting powder was purified by flash chromatography on silica, eluting with a gradient of 0 to 5% MeOH in DCM. Pure fractions were evaporated to afford the title compound (0.660 g, 46%); 1H NMR (400 MHz, CDCl3) 1.39 (3H, d), 1.53-1.61 (2H, m), 1.78-1.84 (2H, m), 2.43 (1H, s), 3.16 (3H, s), 3.39 (1H, td), 3.63 (1H, td), 3.77 (1H, dd), 3.86 (1H, d), 4.07 (1H, dd), 4.17 (1H, d), 4.53 (1H, s), 6.92 (1H, s), 7.34 (1H, dd), 7.41-7.47 (1H, m), 8.06 (1H, d), 8.43 (1H, d), 9.60 (1H, s); m/z: (ES+) MH+, 413.12. Chiral HPLC: (HP1100 System 4, 5 mum Chiralcel OJ-H (250 mm×4.6 mm) column eluting with Heptane/EtOH/MeOH/TEA 50/25/25/0.1) Rf, 8.113 98.9%.
  • 24
  • [ 1352280-97-7 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
1: 62% 2: 39% With triethylamine In methanol; ethanol; 2-Methylpentane 2.01; 2.02 The two samples of 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-(S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine were combined (4.56 g, 11.05 mmol) and purified by preparative chiral chromatography on a Merck 100 mm ChiralCel OJ column (1550 g), eluting isocratically with 50% isohexane in EtOH/MeOH (1:1) (modified with TEA) as eluent. The fractions containing the first eluting compound were combined and evaporated. The residue was dissolved in DCM (50 ml) and concentrated in vacuo onto silica (20 g). The resulting powder was purified by flash chromatography on silica, eluting with a gradient of 0 to 7% MeOH in DCM. Pure fractions were evaporated to afford the title compound 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-((R)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (1.789 g, 39%); 1H NMR (400 MHz, DMSO-d6) 1.27 (3H, d), 1.43 (1H, dd), 1.46-1.58 (2H, m), 1.69-1.77 (1H, m), 3.10 (3H, s), 3.27 (1H, td), 3.51 (1H, td), 3.66 (1H, dd), 3.80 (1H, d), 3.85 (1H, s), 4.01 (1H, dd), 4.19 (1H, d), 4.59 (1H, s), 6.99 (1H, s), 7.22 (1H, dd), 7.54-7.63 (1H, m), 7.94 (1H, d), 8.33 (1H, d), 11.80 (1H, s); m/z: (ES+) MH+, 413.50. Chiral HPLC: (Kronlab prep system, 20 μm Chiralpak OJ (250 mm×4.6 mm) column eluting with Hexane/EtOH/MeOH/TEA 50/25/25/0.1) Rf, 9.684 99.4%.The fractions containing the second eluting compound were combined and evaporated. The residue was dissolved in DCM (50 ml) and concentrated in vacuo onto silica gel (20 g). The resulting powder was purified by flashchromatography on silica, eluting with a gradient of 0 to 7 % MeOH in DCM. Pure fractions were evaporated to afford the title compound 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-((S)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (2.85 g, 62%); 1H NMR (400 MHz, DMSO-d6) 1.27 (3H, d), 1.38-1.46 (1H, dd), 1.51 (2H, m), 1.72-1.81 (1H, m), 3.10 (3H, s), 3.26 (1H, td), 3.51 (1H, td), 3.66 (1H, dd), 3.80 (1H, d), 3.84 (1H, s), 3.94-4.04 (1H, dd), 4.21 (1H, d), 4.56 (1H, s), 6.99 (1H, s), 7.22 (1H, dd), 7.53-7.63 (1H, m), 7.94 (1H, d), 8.33 (1H, d), 11.80 (1H, s); m/z: (ES+) MH+, 413.53. Chiral HPLC: (Kronlab prep system, 20 μm Chiralpak OJ (250 mm×4.6 mm) column eluting with Hexane/EtOH/MeOH/TEA 50/25/25/0.1) Rf, 18.287 99.3%.
  • 25
  • [ 1352227-15-6 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 5: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 6 steps 1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 5: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 6: triethylamine / ethanol; 2-Methylpentane; methanol
  • 26
  • [ 1352227-15-6 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 2.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 4.2: 18 h / 50 °C
Multi-step reaction with 4 steps 1.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 2.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 3.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 4.2: 18 h / 50 °C
Multi-step reaction with 4 steps 1.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 4.2: 18 h / 50 °C
Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 5 steps 1.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2.1: triethylamine / ethanol; 2-Methylpentane 3.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 4.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 5.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1.1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2.1: triethylamine / ethanol; 2-Methylpentane 3.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 5.2: 18 h / 50 °C
Multi-step reaction with 5 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 5: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 5 steps 1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 0.17 h / 25 °C 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 5: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 5 steps 1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 5: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 5 steps 1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2: triethylamine / ethanol; 2-Methylpentane 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 5 steps 1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2: triethylamine / ethanol; 2-Methylpentane 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 6 steps 1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2: triethylamine / ethanol; 2-Methylpentane 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 6 steps 1: sodium periodate / ethyl acetate; water; methanol / 16 h / 20 °C 2: triethylamine / ethanol; 2-Methylpentane 3: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 4: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 5: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 6: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 4 steps 1: sodium periodate / water; methanol; ethyl acetate / 16 h / 20 °C / Inert atmosphere 2: dirhodium tetraacetate; [bis(acetoxy)iodo]benzene; magnesium oxide / dichloromethane / 16 h / 20 °C 3: tetraoctyl ammonium bromide; sodium hydroxide / 2-methyltetrahydrofuran / 4.17 h / 20 °C / Inert atmosphere 4: bis-triphenylphosphine-palladium(II) chloride; sodium carbonate / water; 1,2-dimethoxyethane / 2 h / 90 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: (2R)-2-amino-3,3-dimethylbutan-1-ol; bis(acetylacetonato) oxovanadium(IV); dihydrogen peroxide; 3-(tert-butyl)-5-nitrosalicylaldehyde / dichloromethane / 24 h / 20 °C 2: [bis(acetoxy)iodo]benzene; magnesium oxide; dirhodium tetraacetate / 24 h / 20 °C 3: sodium hydroxide / 2-methyltetrahydrofuran; water / 24 h / 20 °C 4: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; ethanol / 0.33 h / 110 °C

Reference: [1]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[2]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[3]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[4]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[5]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[6]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[7]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[8]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[9]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[10]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[11]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[12]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[13]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[14]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[15]Current Patent Assignee: PFIZER INC; TAKEDA PHARMACEUTICAL COMPANY LIMITED; ASTRAZENECA PLC - US2011/306613, 2011, A1
[16]Foote, Kevin M.; Nissink, J. Willem M.; McGuire, Thomas; Turner, Paul; Guichard, Sylvie; Yates, James W. T.; Lau, Alan; Blades, Kevin; Heathcote, Dan; Odedra, Rajesh; Wilkinson, Gary; Wilson, Zena; Wood, Christine M.; Jewsbury, Philip J. [Journal of Medicinal Chemistry, 2018, vol. 61, # 22, p. 9889 - 9907]
[17]Current Patent Assignee: JIANGSU JICUI MOLECULE ENGINEERING RES INSTITUTE - CN111646985, 2020, A
  • 27
  • [ 1352227-18-9 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 2: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 4: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 5 steps 1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 2: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 4: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 5: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 4 steps 1: dirhodium tetraacetate; [bis(acetoxy)iodo]benzene; magnesium oxide / dichloromethane / 96 h / 20 °C 2: tetraoctyl ammonium bromide; sodium hydroxide / water; 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 3: bis-triphenylphosphine-palladium(II) chloride; sodium carbonate / water; 1,2-dimethoxyethane / 6 h / 90 °C / Inert atmosphere 4: sodium hydroxide / water; 1,2-dimethoxyethane / 18 h / 50 °C / Inert atmosphere
  • 28
  • [ 1352227-18-9 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: triethylamine / ethanol; 2-Methylpentane 2.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 4.2: 18 h / 50 °C
Multi-step reaction with 3 steps 1.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 2.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 3.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 3.2: 18 h / 50 °C
Multi-step reaction with 3 steps 1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 2: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: triethylamine / ethanol; 2-Methylpentane 2.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 3.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 4.2: 18 h / 50 °C
Multi-step reaction with 4 steps 1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 2: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 4: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 4 steps 1: triethylamine / ethanol; 2-Methylpentane 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: triethylamine / ethanol; 2-Methylpentane 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 5 steps 1: triethylamine / ethanol; 2-Methylpentane 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 5: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 5 steps 1: triethylamine / ethanol; 2-Methylpentane 2: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 3: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 4: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 5: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C

  • 29
  • [ 1352232-88-2 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
1: 36% 2: 44% With sodium hydroxide In 1,2-dimethoxyethane; water at 50℃; for 18h; 2.01; 2.02 EXAMPLE 2.01 AND EXAMPLE 2.024-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-((S)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine, and 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-((R)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine; (3R)-3-Methyl-4-(6-(1-(S-methylsulfonimidoyl)cyclopropyl)-2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)morpholine (1.67 g, 2.95 mmol) was dissolved in DME:water 4:1 (60 ml) and heated to 50° C. Sodium hydroxide, 2M aqueous solution (2.58 ml, 5.16 mmol) was then added and heating continued for 18 hours. The reaction mixture was acidified with 2M HCl (2 ml) to pH5. The reaction mixture was evaporated to dryness and the residue dissolved in EtOAc (250 ml), and washed with water (200 ml). The organic layer was dried over MgSO4, filtered and evaporated onto silica gel (10 g). The resulting powder was purified by flash chromatography on silica, eluting with a gradient of 0 to 7% MeOH in DCM. Pure fractions were evaporated and the residue was purified by preparative chiral chromatography on a Merck 50 mm, 20 μm ChiralCel OJ column, eluting isocratically with 50% isohexane in EtOH/MeOH (1:1) (modified with TEA) as eluent. The fractions containing the desired compound were evaporated to dryness to afford the title compound: 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-((R)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (0.538 g, 44%) as the first eluting compound; 1H NMR (400 MHz, DMSO-d6) 1.29 (3H, d), 1.51 (3H, m), 1.70-1.82 (1H, m), 3.11 (3H, s), 3.28 (1H, m, obscured by water peak), 3.48-3.60 (1H, m), 3.68 (1H, dd), 3.75-3.87 (2H, m), 4.02 (1H, 4.19 (1H, d), 4.60 (1H, s), 7.01 (1H, s), 7.23 (1H, dd), 7.51-7.67 (1H, m), 7.95 (1H, d), 8.34 (1H, d), 11.76 (1H, s); m/z: (ES+) MH+, 413.12. Chiral HPLC: (HP1100 System 4, 5 μm Chiralcel OJ-H (250 mm×4.6 mm) column eluting with iso-Hexane/EtOH/MeOH/TEA 50/25/25/0.1) Rf, 9.013 >99%. Crystals were grown and isolated by slow evaporation to dryness in air from EtOAc. These crystals were used to obtain the structure shown in FIG. 1 by X-Ray diffraction (see below). Example 2.02: 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-((R)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (326 mg, 0.79 mmol) was dissolved in DCM (3 ml). Silica gel (0.5 g) was added and the mixture concentrated in vacuo. The resulting powder was purified by flash chromatography on silica, eluting with a gradient of 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness and the residue was crystallized from EtOAc/n-heptane to afford 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-((R)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (256 mg, 79%) as a white crystalline solid; 1H NMR (400 MHz, DMSO-d6) 1.29 (3H, d), 1.39-1.60 (3H, m), 1.71-1.81 (1H, m), 3.10 (3H, d), 3.21-3.29 (1H, m), 3.52 (1H, td), 3.67 (1H, dd), 3.80 (2H, t), 4.01 (1H, dd), 4.19 (1H, d), 4.59 (1H, s), 7.01 (1H, s), 7.23 (1H, dd), 7.54-7.62 (1H, m), 7.95 (1H, d), 8.34 (1H, d), 11.75 (1H, s). DSC (Mettler-Toledo DSC 820, sample run at a heating rate of 10° C. per minute from 30° C. to 350° C. in a pierced aluminium pan) peak, 224.11° C.and the title compound: 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-((S)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (0.441 g, 36%) as the second eluting compound; 1H NMR (400 MHz, DMSO-d6) 1.28 (3H, d), 1.40-1.58 (3H, m), 1.70-1.80 (1H, m), 3.10 (3H, d), 3.23-3.27 (1H, m), 3.51 (1H, dt), 3.66 (1H, dd), 3.80 (2H, d), 4.01 (1H, dd), 4.21 (1H, d), 4.56 (1H, s), 6.99 (1H, s), 7.22 (1H, dd), 7.54-7.61 (1H, m), 7.94 (1H, d), 8.33 (1H, d), 11.75 (1H, s); m/z: (ES+) MH+, 413.12. Chiral HPLC: (HP1100 System 4, 5 μm Chiralcel OJ-H (250 mm×4.6 mm) column eluting with iso-Hexane/EtOH/MeOH/TEA 50/25/25/0.1) Rf, 15.685 >99%. Example 2.01: 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-(S)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (66.5 mg) was purified by crystallisation from EtOH/water to afford 4-{4-[(3R)-3-methylmorpholin-4-yl]-6-[1-(S)-S-methylsulfonimidoyl)cyclopropyl]pyrimidin-2-yl}-1H-pyrrolo[2,3-b]pyridine (0.050 g); 1H NMR (400 MHz, CDCl3) 1.40 (3H, d), 1.59 (2H, s), 1.81 (2H, s), 2.41 (1H, s), 3.16 (3H, s), 3.39 (1H, td), 3.59-3.67 (1H, m), 3.77 (1H, dd), 3.86 (1H, d), 4.07 (1H, dd), 4.17 (1H, d), 4.54 (1H, s), 6.91 (1H, s), 7.34 (1H, t), 7.43 (1H, t), 8.05 (1H, d), 8.41 (1H, d), 9.14 (1H, s).
1: 44% 2: 36% With sodium hydroxide In 1,2-dimethoxyethane; water at 50℃; for 18h; Inert atmosphere;
Multi-step reaction with 2 steps 1: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 2: triethylamine / ethanol; 2-Methylpentane; methanol
  • 30
  • [ 1352412-35-1 ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 2: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 3 steps 1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 2: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 3: triethylamine / ethanol; 2-Methylpentane; methanol
  • 31
  • [ 1352227-16-7 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 2.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 3.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 3.2: 18 h / 50 °C
Multi-step reaction with 3 steps 1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 2: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 96 h / 20 °C 2: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 4: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 3 steps 1: dirhodium tetraacetate; [bis(acetoxy)iodo]benzene; magnesium oxide / dichloromethane / 16 h / 20 °C 2: tetraoctyl ammonium bromide; sodium hydroxide / 2-methyltetrahydrofuran / 4.17 h / 20 °C / Inert atmosphere 3: bis-triphenylphosphine-palladium(II) chloride; sodium carbonate / water; 1,2-dimethoxyethane / 2 h / 90 °C / Inert atmosphere

  • 32
  • [ 1352227-17-8 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 2.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 3.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 3.2: 18 h / 50 °C
Multi-step reaction with 3 steps 1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 2: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 4 steps 1: magnesium oxide; [bis(acetoxy)iodo]benzene / dirhodium tetraacetate / dichloromethane / 48 h / 20 °C 2: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 3: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 4: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
Multi-step reaction with 3 steps 1: [bis(acetoxy)iodo]benzene; magnesium oxide; dirhodium tetraacetate / 24 h / 20 °C 2: sodium hydroxide / 2-methyltetrahydrofuran; water / 24 h / 20 °C 3: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / water; ethanol / 0.33 h / 110 °C

  • 33
  • [ 1352227-19-0 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 2.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2.2: 18 h / 50 °C
Multi-step reaction with 2 steps 1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 2: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 2: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 3: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
  • 34
  • N-[({2-chloro-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl}methyl)(methyl)oxido-λ6-sulfanylidene]-2,2,2-trifluoroacetamide [ No CAS ]
  • [ 1352226-88-0 ]
  • [ 1352226-87-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 2: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 3: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C
Multi-step reaction with 4 steps 1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 2: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 6 h / 90 °C / Inert atmosphere 3: sodium hydroxide / 1,2-dimethoxyethane; water / 18 h / 50 °C 4: triethylamine / ethanol; 2-Methylpentane; methanol
Multi-step reaction with 3 steps 1: tetraoctyl ammonium bromide; sodium hydroxide / water; 2-methyltetrahydrofuran / 48 h / 20 °C / Inert atmosphere 2: bis-triphenylphosphine-palladium(II) chloride; sodium carbonate / water; 1,2-dimethoxyethane / 6 h / 90 °C / Inert atmosphere 3: sodium hydroxide / water; 1,2-dimethoxyethane / 18 h / 50 °C / Inert atmosphere
  • 35
  • N-[({2-chloro-6-[(3R)-3-methylmorpholin-4-yl]pyrimidin-4-yl}methyl)(methyl)oxido-λ6-sulfanylidene]-2,2,2-trifluoroacetamide [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 2.1: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 4 h / 90 °C / Inert atmosphere 2.2: 18 h / 50 °C
Multi-step reaction with 2 steps 1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 2: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 6 h / 85 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: sodium hydroxide / tetraoctyl ammonium bromide / 2-methyltetrahydrofuran / 24 h / 20 °C / Inert atmosphere 2: sodium carbonate / bis-triphenylphosphine-palladium(II) chloride / 1,2-dimethoxyethane; water / 2 h / 90 °C / Inert atmosphere 3: sodium hydroxide / 1,2-dimethoxyethane; water / 96 h / 20 °C
  • 36
  • [ 1352232-89-3 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
90% With methanol; water; sodium hydroxide at 0℃; for 3h; 2.1; 3.1 Step 1: Add 2-1 (2.2g, 3.8mmol) to the reaction flask and dissolve it in MeOH (100mL), stir, and after the reaction solution is cooled to 0°C, add an aqueous solution of NaOH (0.8g, 19mmol, 50%), After 3 hours of reaction, TLC monitoring showed that the raw material reaction was complete. Water (100 mL) was added to quench the reaction, extracted with DCM (2×200 mL), separated into layers, the organic phase was washed with saturated sodium chloride, dried with anhydrous sodium sulfate, and concentrated in vacuo. A crude yellow solid was obtained, which was passed through column chromatography on silica gel, PE:EA-MeOH:DCM (1:1-1:10) to obtain a yellow solid 2-2 (1.5g, yield 90%)
With sodium hydroxide In 1,2-dimethoxyethane; water at 20℃; for 96h; 2.01; 2.02 Example 2.02 can also be prepared as follows:2M NaOH solution (14.86 ml, 29.72 mmol) was added to (3R)-3-methyl-4-(6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)-2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)morpholine (8.42 g, 14.86 mmol) in DME:water 4:1 (134 ml). The resulting solution was stirred at RT for 4 days. In a separate experiment, 2M NaOH solution (7.06 ml, 14.12 mmol) was added to (3R)-3-methyl-4-(6-(1-((R)-S-methylsulfonimidoyl)cyclopropyl)-2-(1-tosyl-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)morpholine (4 g, 7.06 mmol) in DME:water 4:1 (63.5 ml). The resulting solution was stirred at RT for 18 hours. The reaction mixtures from the two procedures were combined and then neutralised with 2M HCl. The mixture was evaporated onto reverse phase silica gel (40 g) and the resulting powder was purified by flash chromatography on reverse phase silica, eluting with a gradient of 20 to 60% ACN in water with 1% ammonia. Pure fractions were evaporated to dryness to afford the title compound (7.05 g, 78%); 1H NMR (400 MHz, DMSO-d6) 1.27 (3H, t), 1.39-1.6 (3H, m), 1.7-1.8 (1H, m), 3.10 (3H, s), 3.26 (1H, d), 3.52 (1H, td), 3.67 (1H, dd), 3.80 (2H, t), 3.97-4.02 (1H, m), 4.19 (1H, d), 4.59 (1H, s), 7.00 (1H, s), 7.22 (1H, dd), 7.53-7.61 (1H, m), 7.95 (1H, d), 8.33 (1H, d), 11.75 (1H, s); m/z: (ES+) MH+, 413.08.
  • 37
  • [ 35120-12-8 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: 1,1'-carbonyldiimidazole / 2-methyltetrahydrofuran / 4.5 h / 20 °C / Large scale 1.2: 15 h / 40 - 45 °C / Large scale 2.1: potassium <i>tert</i>-butylate / ethanol; tetrahydrofuran / 10 h / 78 °C / Large scale 3.1: chloroacetic acid / water / 9 h / 95 °C / Large scale 4.1: trichlorophosphate; N,N-diethylaniline / water / 7 h / 90 - 100 °C / Large scale 4.2: 2 h / 0 - 10 °C / pH 5 - 8 / Large scale 5.1: triethylamine; potassium carbonate / dimethyl sulfoxide / 15 h / 20 °C / Large scale 6.1: cyclohexanonemonooxygenase Rhodococcus Ruber; NADP; ketoreductase; dipotassium hydrogen phosphate trihydrate; hydrogenchloride; oxygen / water; isopropyl alcohol / 10 h / 30 °C / Large scale; Enzymatic reaction 7.1: [bis(acetoxy)iodo]benzene; ammonium carbamate / methanol; toluene / 20 h / 0 - 10 °C / Large scale; Enzymatic reaction 8.1: potassium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / ethanol; water / 4 h / 80 °C / Inert atmosphere; Large scale; Enzymatic reaction
Multi-step reaction with 8 steps 1.1: 1,1'-carbonyldiimidazole / 2-methyltetrahydrofuran / 6 h / 20 °C / Large scale 1.2: 20 h / 40 - 45 °C / Large scale 1.3: 1 h / Large scale 2.1: potassium <i>tert</i>-butylate / ethanol / 23 h / 78 °C / Large scale 3.1: water / 7 h / 95 °C / Large scale 4.1: trichlorophosphate; N,N-diethylaniline / 6 h / 90 - 100 °C / Large scale 5.1: potassium carbonate; triethylamine / dimethyl sulfoxide / 18 h / 20 °C 6.1: cyclohexanone monooxygenase Rhodococcus ruber; NADPH; keto-reductase; potassium hydrogenphosphate trihydrate; isopropyl alcohol / aq. phosphate buffer / 16 h / 30 °C / Large scale; Enzymatic reaction 7.1: [bis(acetoxy)iodo]benzene; ammonium carbamate / methanol; toluene / 20 h / 0 - 10 °C 8.1: bis-triphenylphosphine-palladium(II) chloride; potassium phosphate / water; ethanol / 17 h / 75 °C / Inert atmosphere; Large scale 8.2: 8 h / 60 °C / Large scale
Multi-step reaction with 8 steps 1.1: 1,1'-carbonyldiimidazole / 2-methyltetrahydrofuran / 6 h / 20 °C / Large scale 1.2: 20 h / 40 - 45 °C / Large scale 1.3: 1 h / Large scale 2.1: potassium <i>tert</i>-butylate / ethanol / 23 h / 78 °C / Large scale 3.1: water / 7 h / 95 °C / Large scale 4.1: trichlorophosphate; N,N-diethylaniline / 6 h / 90 - 100 °C / Large scale 5.1: potassium carbonate; triethylamine / dimethyl sulfoxide / 19 h / 20 °C / Large scale 6.1: cyclohexanone monooxygenase Rhodococcus ruber; NADPH; keto-reductase; potassium hydrogenphosphate trihydrate; isopropyl alcohol / aq. phosphate buffer / 16 h / 30 °C / Large scale; Enzymatic reaction 7.1: [bis(acetoxy)iodo]benzene; ammonium carbamate / methanol; toluene / 20 h / 0 - 10 °C 8.1: bis-triphenylphosphine-palladium(II) chloride; potassium phosphate / water; ethanol / 17 h / 75 °C / Inert atmosphere; Large scale 8.2: 8 h / 60 °C / Large scale
  • 38
  • [ 942919-26-8 ]
  • (3R)-4-{2-chloro-6-[1-(methylsulfonimidoyl)cyclopropyl]-4-pyrimidinyl}-3-methylmorpholine hydrochloride [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
77% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In ethanol; water at 80℃; for 4h; Inert atmosphere; Large scale; Enzymatic reaction; 10 Example 10: Preparation of 4-{4-[(3R)-3-methyl-4-morpholinyll-6-[l-(S- methylsulfonimidoyl)cvclopropyll-2-pyrimidinyl}-lH-pyrrolo[2.,3-blpyridine Anhydrous ethanol (376 kg) was charged to the vessel. (3R)-4-{2-Chloro-6-[l-(S- methylsulfonimidoyl)cyclopropyl]-4-pyrimidinyl}-3-methylmorpholine hydrochloride (28.5 kg, 77.68 mol) was charged to the vessel. Stirring was started. A solution of anhydrous potassium carbonate (35.1 kg, 256 mol) in water (136 kg) was charged to the vessel. The vessel was inerted with nitrogen. 4-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrrolo[2,3-b]pyridine (25.4 kg, 101.0 mol) was charged to the vessel. [l,r-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.250 kg, 1.709 mol) was charged to the vessel. The contents of the vessel were heated to approximately 80 °C for 4 hours. The contents of the vessel were cooled to approximately 25 °C then a mixture of activated carbon (1.8 kg) and water (24.8 kg) was charged to the vessel. The contents of the vessel were stirred for 4 hours, then the solid was removed by fdtration and the filter cake was washed with ethanol (39 kg). The filtrate was transferred to a clean vessel. The contents of the vessel were concentrated by reduced pressure distillation to a total volume of approximately 100 L. Ethyl acetate (86 kg) was charged to the vessel and the contents were stirred for 1 hour at approximately 25 °C, then stirring was stopped and the layers were partitioned. The aqueous layer was re-charged to the vessel. Ethyl acetate (86 kg) was charged to the vessel and the contents were stirred for 30 minutes at approximately 25°C, then stirring was stopped and the layers were partitioned. The organic layers were combined in the vessel. Water (32 kg) was charged to the vessel and the contents were stirred for 30 minutes at approximately 25°C, then stirring was stopped and the aqueous layer was removed. Silica thiol (24.2 kg) was charged to the vessel. The contents of the vessel were stirred at approximately 25 °C for 8 hours. The solid was removed by filtration and the filter cake was washed with ethyl acetate (25 kg). The filtrate was transferred to a clean vessel. The contents of the vessel were concentrated by reduced pressure distillation to a total volume of approximately 65 L. 1 -Butanol (40 kg) was charged to the vessel, then the contents of the vessel were concentrated by reduced pressure distillation to a total volume of approximately 65 L. Butanol (40 L) was charged to the vessel, then the contents of the vessel were concentrated by reduced pressure distillation to a total volume of approximately 65 L. (0299) The stirred contents of the vessel were heated to approximately 75 °C, then seed crystal (17 g) was charged to the vessel. The mixture was stirred for 3 approximately 2 hours, then the mixture was cooled to approximately 20 °C. n-Heptane (76 kg) was charged to the vessel and the mixture was stirred at approximately 20 °C for a further 2 hours. The solid was collected by filtration. The filter cake was washed with a mixture of 1 -butanol (5 kg) and n-heptane (23 kg) to yield 4-{4-[(3R)-3- methyl-4-morpholinyl]-6-[l-(S-methylsulfonimidoyl)cyclopropyl]-2-pyrimidinyl}-lH-pyrrolo[2,3- b]pyridine (25.5 kg, 97% w/w, 60.0 mol, 77% yield) as a solid. 1H NMR (500 MHz, DMSO, 27°C) 1.29 (3H, d), 1.42 - 1.49 (1H, m), 1.55 (2H, ddt), 1.78 (1H, dq), 3.14 (3H, s), 3.29 (1H, td), 3.53 (1H, td), 3.68 (1H, dd), 3.81 (1H, d), 3.88 (1H, s), 4.02 (1H, dd), 4.20 (1H, d), 4.60 (1H, s), 7.02 (1H, s), 7.26 (1H, dd), 7.59 - 7.65 (1H, m), 7.98 (1H, d), 8.36 (1H, d), 11.83 (1H, s). MS: (M+H)+ 413.
  • 39
  • [ 942919-26-8 ]
  • (3R)-4-{2-chloro-6-[1-(S-methylsulfonimidoyl)-cyclopropyl]-4-pyrimidinyl}-3-methylmorpholine hydrochloride [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
70% Stage #1: 4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine; (3R)-4-{2-chloro-6-[1-(S-methylsulfonimidoyl)-cyclopropyl]-4-pyrimidinyl}-3-methylmorpholine hydrochloride With bis-triphenylphosphine-palladium(II) chloride; potassium phosphate In ethanol; water at 75℃; for 17h; Inert atmosphere; Large scale; Stage #2: With L-Cysteine In 2-methyltetrahydrofuran; ethanol; water at 60℃; for 8h; Large scale;
  • 40
  • [ 1352226-88-0 ]
  • [ 124-63-0 ]
  • N-((R)-methyl(1-(6-((R)-3-methylmorpholino)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)cyclopropyl)(oxo)-6-sulfinyl)methanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With dmap; triethylamine In dichloromethane at 0 - 20℃; for 16h; 2.2 Step 2: Add 2-2 (500mg, 1.2mmol), DMAP (14mg, 0.12mmol) in DCM (20mL) to the reaction flask and stir, the reaction solution is cooled to 0, TEA (363mg, 3.6mmol) and MsCl (276mg, 2.4mmol) was reacted at room temperature for 16h; TLC monitoring showed that the reaction of the raw materials was complete, 50mL of water was added, DCM (2×50mL) was added, the layers were separated, the organic phase was washed with saturated sodium chloride, dried with anhydrous sodium sulfate, and vacuum The organic phase was concentrated, and column chromatography silica gel was passed through PE:EA-DCM:MeOH (1:1-15:1) to obtain a white solid 2 (400mg, yield 60%).
  • 41
  • [ 1352226-88-0 ]
  • [ 139631-62-2 ]
  • N-((R)-methyl(1-(6-((R)-3-methylmorpholino)-2-(1H-pyrrolo[2,3-b]pyridin-4-yl)pyrimidin-4-yl)cyclopropyl)(oxo)-6-sulfinyl)cyclopropanesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
8% With dmap; triethylamine In dichloromethane at 0 - 20℃; for 16h; 3.2 Step 2: Add 3-2 (100mg, 0.24mmol), DMAP (2.8mg, 0.024mmol) in DCM (10mL) into the reaction flask and stir, the reaction solution is cooled to 0, TEA (75mg, 0.72mmol) is added It was reacted with cyclopropanesulfonyl chloride (56mg, 0.48mmol) at room temperature for 16h; TLC monitoring showed that the reaction of the raw material was 30%, 50mL of water was added, DCM (2×50mL) was added, the layers were separated, the organic phase was washed with saturated sodium chloride, anhydrous After drying over sodium sulfate, the organic phase was concentrated in vacuo, and column chromatography silica gel was passed through PE:EA-DCM:MeOH (1:1-15:1) to obtain a white solid (18mg, yield 8%).
  • 42
  • 1-benzyl-4-(4,6-dichloropyrimidin-2-yl)-1H-pyrrolo[2,3-b]pyridine [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 7 h / -78 °C / Inert atmosphere 2.1: trifluoroacetic acid / dichloromethane / 3.5 h / 20 °C / Inert atmosphere 2.2: 72 h / 80 °C 3.1: sodium hydride; benzo-15-crown-5 / 1,4-dioxane / 0.33 h / 20 °C / Inert atmosphere 3.2: 18 h / 50 °C / Inert atmosphere 4.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 5.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 5.2: 4 h / 20 °C
  • 43
  • (R)-N-((1-(2-(1-benzyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-6-chloropyrimidin-4-yl)cyclopropyl)(tert-butyl)(oxo)-λ6-sulfaneylidene)pivalamide [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: trifluoroacetic acid / dichloromethane / 3.5 h / 20 °C / Inert atmosphere 1.2: 72 h / 80 °C 2.1: sodium hydride; benzo-15-crown-5 / 1,4-dioxane / 0.33 h / 20 °C / Inert atmosphere 2.2: 18 h / 50 °C / Inert atmosphere 3.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 4.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 4.2: 4 h / 20 °C
  • 44
  • N-((R)-(1-(2-(1-benzyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-6-((R)-3-methylmorpholino)pyrimidin-4-yl)cyclopropyl)sulfinyl)pivalamide [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sodium hydride; benzo-15-crown-5 / 1,4-dioxane / 0.33 h / 20 °C / Inert atmosphere 1.2: 18 h / 50 °C / Inert atmosphere 2.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 3.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 3.2: 4 h / 20 °C
  • 45
  • N-((R)-(1-(2-(1-benzyl-1H-pyrrolo[2,3-b]pyridin-4-yl)-6-((R)-3-methylmorpholino)pyrimidin-4-yl)cyclopropyl)(methyl)(oxo)-λ6-sulfaneylidene)pivalamide [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 2.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 2.2: 4 h / 20 °C
  • 46
  • C27H30N6O2S [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: C27H30N6O2S With sodium hydride In tetrahydrofuran; dimethyl sulfoxide at 20℃; for 0.25h; Stage #2: With potassium-t-butoxide; oxygen In tetrahydrofuran at 20℃; for 4h;
  • 47
  • [ 1422965-33-0 ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: anhydrous potassium acetate; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / 1,4-dioxane / 6 h / Inert atmosphere 2.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate / water monomer; toluene / 0.58 h / 90 °C / Inert atmosphere 3.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 7 h / -78 °C / Inert atmosphere 4.1: trifluoroacetic acid / dichloromethane / 3.5 h / 20 °C / Inert atmosphere 4.2: 72 h / 80 °C 5.1: sodium hydride; benzo-15-crown-5 / 1,4-dioxane / 0.33 h / 20 °C / Inert atmosphere 5.2: 18 h / 50 °C / Inert atmosphere 6.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 7.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 7.2: 4 h / 20 °C
Multi-step reaction with 7 steps 1.1: anhydrous potassium acetate; palladium (II) [1,1'-bis(diphenylphosphanyl)ferrocene] dichloride / 1,4-dioxane / 6 h / Inert atmosphere 2.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate / toluene; water monomer / 0.58 h / 90 °C / Inert atmosphere 3.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 7 h / -78 °C / Inert atmosphere 4.1: trifluoroacetic acid / dichloromethane / 3.5 h / 20 °C / Inert atmosphere 4.2: 72 h / 80 °C 5.1: sodium hydride; benzo-15-crown-5 / 1,4-dioxane / 0.33 h / 20 °C / Inert atmosphere 5.2: 18 h / 50 °C / Inert atmosphere 6.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 7.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 7.2: 4 h / 20 °C
  • 48
  • 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate / water monomer; toluene / 0.58 h / 90 °C / Inert atmosphere 2.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 7 h / -78 °C / Inert atmosphere 3.1: trifluoroacetic acid / dichloromethane / 3.5 h / 20 °C / Inert atmosphere 3.2: 72 h / 80 °C 4.1: sodium hydride; benzo-15-crown-5 / 1,4-dioxane / 0.33 h / 20 °C / Inert atmosphere 4.2: 18 h / 50 °C / Inert atmosphere 5.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 6.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 6.2: 4 h / 20 °C
Multi-step reaction with 6 steps 1.1: [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate / toluene; water monomer / 0.58 h / 90 °C / Inert atmosphere 2.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 7 h / -78 °C / Inert atmosphere 3.1: trifluoroacetic acid / dichloromethane / 3.5 h / 20 °C / Inert atmosphere 3.2: 72 h / 80 °C 4.1: sodium hydride; benzo-15-crown-5 / 1,4-dioxane / 0.33 h / 20 °C / Inert atmosphere 4.2: 18 h / 50 °C / Inert atmosphere 5.1: hydrogenchloride / water monomer; methanol / 10 h / 70 °C 6.1: sodium hydride / tetrahydrofuran; dimethyl sulfoxide / 0.25 h / 20 °C 6.2: 4 h / 20 °C
  • 49
  • C33H39N5O3S [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
87% Stage #1: C33H39N5O3S With hydrogenchloride In methanol at 70℃; Stage #2: With potassium-t-butoxide; oxygen In methanol; dimethyl sulfoxide at 20℃;
  • 50
  • C32H38N6O5S2 [ No CAS ]
  • [ 1352226-88-0 ]
YieldReaction ConditionsOperation in experiment
89% With sodium hydroxide In methanol at 70℃;
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