630-580-1088 sales@ambeed.com
Structure Search

List Search MOL Search Structure Search

0
Chemistry
Asymmetric Synthesis >>Chiral Building BlocksChiral Catalysts, Chiral Ligands and Chiral ReagentsChiral Resolution ReagentsBoronic acids/esters >>Aliphatic BoronsAromatic BoronsOther BoronsOxaborolesCatalysis Chemistry >>Achiral Crown LigandsC-H ActivationCarbon-Donor LigandsChiral Carbon LigandsChiral Crown LigandsChiral Olefin LigandsCross-CouplingCross-Coupling Using Transition Metal CatalystsDACH or Trost LigandsChemical Biology >>Conjugation Chemistry
GlycoscienceLinkers and CrosslinkersNucleic Acid ChemistryPEGylationPeptide ChemistryPhotolabile Protecting GroupHeterocyclic Building Blocks >>AcridinesAliphatic HeterocyclesAromatic HeterocyclesAzetidinesBenzimidazolesBenzisoxazolesBenzodioxansBenzofuransBenzothiazolesInorganic reagents >>Inorganic reagentOrganic Building Blocks >>Acid AnhydridesAcyl Chlorides
AlcoholsAldehydesAliphatic Chain HydrocarbonsAliphatic Cyclic HydrocarbonsAlkenesAlkylsAlkynesOrganometallic Reagents >>Grignard ReagentsOrganoarsenicOrganobismuthOrganoboronOrganogermaniumOrganolithiumOrganomercuryOrganosiliconOrganotinSpecialty Synthesis >>Enzyme-Mediated SynthesisFluorous SynthesisIonic Liquids
Solid Supported SynthesisStains and Dyes >>Acid DyesAzoic DyesBasic DyesDirect DyesDisperse DyesDye IntermediatesMordant DyesOil DyesOther Stains and DyesSynthetic Reagents >>Acids and BasesC-C Bond FormationC-X Bond Formation (Halogen)C-X Bond Formation (Non-Halogen)Chelation and Complexation CompoundsCondensation AgentsCouplingDehydrating ReagentsFluorination Reagent
Pharmaceutical Intermediates
Analgesics >>BenzhydrocodoneBicifadineCapsaicinCelecoxibDebio-0827DexamethasoneElagolix SodiumEsketamine HydrochlorideIbuprofen sodiumAnesthetics >>CiprofolEsketamine HydrochlorideFospropofol Fospropofol DisodiumLevobupivacaine RemimazolamRemimazolam BesilateRemimazolam besylateRopivacaineAnti-Addiction Agents >>Kakonein
Lofexidine HydrochlorideVarenicline Anti-inflammatory Agents >>ApremilastAsunaprevirATB-346 RelatedBalsalazide BaricitinibBencycloquidium BromideBudesonideCefiderocol Sulfate TosylateCeftaroline Fosamil AcetateAntibacterials >>AFN-1252 RelatedAlatrofloxacin Bedaquiline FumarateBesifloxacin BrilacidinCaspofungin AcetateCefiderocol Sulfate TosylateCefilavancinCeftaroline Fosamil
Anticonvulsants >>BrivaracetamCannabidiolEscitalopram OxalateEslicarbazepine Acetate RelatedFosphenytoinGabapentin EnacarbilJNJ-10234094LacosamideLevetiracetam RelatedAntidementia Agents >>Azeliragon RelatedDavunetideDonepezil HydrochlorideDonepezil RelatedEnsaculinFlorbetaben Flortaucipir F 18Flutemetamol IdalopirdineAntidepressants >>4-Chlorokynurenine
AgomelatineAgomelatine RelatedAllopregnanolone RelatedAmibegronAmitifadineAripiprazole RelatedBasimglurantBefloxatoneAntiemetics >>AprepitantAprepitant RelatedDolasetron RelatedDolasetron Mesylate HydrateFosaprepitant DimeglumineFosaprepitant RelatedOlanzapinePalonosetron RelatedPalonosetron HydrochlorideAntifungals >>Anidulafungin RelatedCabotegravirMore >>
Inhibitors/Agonists
ADC >>ADC AntibodyADC LinkerADC Linker with PayloadADC ToxinAntibody-Drug Conjugates (ADCs)Drug-Linker Conjugates for ADCAngiogenesis >>ALKBcr-AblBTKEGFRFAKFGFRFLT3HER2HIFAnti-infection >>3CLproAntibacterialAntibioticAntifungal
AntiparasiticAntiprotozoalAntiviralArenavirusBVDVApoptosis >>Apoptosis InducerBcl-2Bcl-6BRKc-Mycc-RETC/EBPCARDCaspaseAutophagy >>Atg4ATG4BATTECsAUTACsAutophagyBeclin1
FKBPLC3LRRK2Biochemical Reagent >>Cell Cycle >>AntifolateAPCAurora KinaseBUBCasein KinaseCdc25CDKChkCRISPR/Cas9Cytoskeleton >>ActinArp2/3 ComplexCYTHCytoplasmic dyneinDynaminFAKMore >>
Material Science
Aggregation-Induced Emission >>Other AIE BlocksTetraphenylethylene SeriesCOFs Linkers >>Aldehyde COFs LinkersAlkynyl COFs LinkersAmine COFs LinkersBoric COFs LinkersCyano COFs LinkersMultifunctional COFs linkersOther COFs linkersTriphene seriesElectronic Materials >>Battery MaterialsDye-Sensitized Solar Cell (DSSC) MaterialsElectronic MaterialLiquid Crystal (LC) MaterialsMolecular ConductorsOrganic Light-Emitting Diode (OLED) MaterialsOrganic Solar Cell (OPV) MaterialsOrganic Transistor (OFET) MaterialsPerovskite Solar Cell (PSC) MaterialsMagnetic Materials >>Magnetic Ionic LiquidsMagnetic MaterialMagnetic Metal Complexes
Organic Radicals Material Chemical Compounds >>Ligands for Functional Metal ComplexesLiquid Crystal (LC) Building BlocksPhthalocyanine Building BlocksPolymer and Macromolecule Semiconductor Building BlocksSmall Molecule Semiconductor Building BlocksSolubility Enhancing Reagents Supramolecular Host Materials MOF Ligands >>Carboxylic Acid MOF LigandsCarboxylic Acid Nitrogen-Containing Mixed MOF LigandsNitrogen-Containing MOF LigandsOther MOF ligandsNanomaterials >>Carbon NanomaterialsCeramic MembranesDendrimersGold NanoparticlesIron Oxide NanoparticlesMaterials by ApplicationMesoporous MaterialsMetals and Metal AlloysNano Minerals: NanoclaysOLED Materials >>Dopant
HostHTMOLED IntermediatesOther OLED related materialsOptical Materials >>Coumarin DyesCyanine and Squarylium DyesDCM DyesDipyrromethene DyesFluorescence MaterialsFluorescent ProbesHeat and Pressure Sensitive DyesNear-Infrared (NIR) DyesOrganic Non-Linear Optical (NLO) MaterialsOrganic Pigments >>Organic PigmentOther Materials >>Mateial OtherPolymer Science >>MonomersPolymer AdditivesPolymerization ReagentsPolymersResins
Contact Us
Home Cart 0 Sign in  
Pharmaceutical Intermediates
Antineoplastics
Ruxolitinib Related
Ruxolitinib phosphate
Pharmaceutical Intermediates
Inhibitors/Agonists
Antineoplastics
JAK/STAT Signaling
Ruxolitinib Related
JAK

[ CAS No. 1092939-17-7 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 1092939-17-7
Chemical Structure| 1092939-17-7
Structure of 1092939-17-7 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 1092939-17-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1092939-17-7 ]

SDS Specification
Alternatived Products of [ 1092939-17-7 ]

Product Details of [ 1092939-17-7 ]

CAS No. :1092939-17-7 MDL No. :MFCD18452860
Formula : C17H21N6O4P Boiling Point : -
Linear Structure Formula :- InChI Key :JFMWPOCYMYGEDM-XFULWGLBSA-N
M.W : 404.36 Pubchem ID :25127112
Synonyms :
INCB018424 phosphate;Ruxolitinib (phosphate);INCB 018424 (phosphate);INC 424 (phosphate);INC424;INCB018424

Calculated chemistry of [ 1092939-17-7 ]

Physicochemical Properties

Num. heavy atoms : 28
Num. arom. heavy atoms : 14
Fraction Csp3 : 0.41
Num. rotatable bonds : 4
Num. H-bond acceptors : 8.0
Num. H-bond donors : 4.0
Molar Refractivity : 101.92
TPSA : 170.75 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.75 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.98
Log Po/w (XLOGP3) : 0.03
Log Po/w (WLOGP) : 2.54
Log Po/w (MLOGP) : -0.23
Log Po/w (SILICOS-IT) : 2.74
Consensus Log Po/w : 1.21

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 1.0
Egan : 1.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.47
Solubility : 1.36 mg/ml ; 0.00337 mol/l
Class : Soluble
Log S (Ali) : -3.17
Solubility : 0.275 mg/ml ; 0.000679 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.75
Solubility : 0.00717 mg/ml ; 0.0000177 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.56

Safety of [ 1092939-17-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338-P310 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1092939-17-7 ]

* 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 [ 1092939-17-7 ]

[ 1092939-17-7 ] Synthesis Path-Downstream   1~54

  • 1
  • [ 941678-49-5 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
84% With phosphoric acid; In dichloromethane; isopropyl alcohol; at 20℃;Reflux;Product distribution / selectivity; Method B.; To a solution of (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H -pyrazol-1-yl)-3-cyclopentylpropanenitrile ((R)-12, 54.2 g, 177 mol) in dichloromethane (782 mL) and 2-propanol (104 mL) at reflux was added a solution of phosphoric acid (19.9 g, 0.173 mol, 1.15 equiv) in 2-propanol (34.0 mL) over a period of 47 minutes. Following the acid addition, the resulting mixture was heated to reflux for an additional 1 hour. The mixture was gradually cooled to ambient temperature and stirred for 3 hours. The solids were collected by filtration and washed with dichloromethane (390 mL), followed by n-heptane (390 mL). The solids were partially dried under vacuum at room temperature and then under vacuum at 62 C. to afford <strong>[941678-49-5](R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile</strong> phosphate (60.1 g, 84% yield) as white to off-white crystalline solids. Analysis by chiral HPLC (chiralcel OD, 90:10 hexane/ethanol) gave the enantiopurity as 99.2% ee. 1H NMR (DMSO-d6, 400 MHz) delta 12.11(bs, 1H), 8.79(d, 1H, J=0.59 Hz), 8.67(s, 1H), 8.36(s, 1H), 7.59(q, 1H, J=2.3 Hz), 6.98(q, 1H, J=1.6 Hz), 4.53(td, 1H, J=19.6, 4.4 Hz), 3.22(dq, 2H, J=9.6, 4.3 Hz), 2.40(m, 1H), 1.79(m, 1H), 1.65-1.13(m, 7H). C17H21N6O4P (MW, 404.36), LCMS (EI) m/e 307 (M++H) and m/e 329 (M++Na).
With phosphoric acid; In isopropyl alcohol; at 20℃; for 2h;Heating / reflux; Example 2; Preparation of <strong>[941678-49-5](R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile</strong> phosphoric acid salt; To a test tube was added <strong>[941678-49-5](R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile</strong> (153.5 mg) and phosphoric acid (56.6 mg) followed by isopropyl alcohol (IPA) (5.75 mL). The resulting mixture was heated to clear, cooled to room temperature, and then stirred for another 2 hours. The precipitate was collected by filtration and the cake was washed with 0.6 mL of cold IPA. The cake was dried under vacuum to constant weight to provide the final salt product (171.7 mg).The phosphoric acid salt was shown to be a 1:1 salt by 1H NMR and crystallinity was confirmed by X-ray powder diffraction (XRPD). Differential scanning calorimetry (DSC) gave a sharp melting peak at about 198.66 C. The product showed little weight loss up to 200 C. by TGA.
171.7 mg With phosphoric acid; In isopropyl alcohol; at 20℃;Heating; To a test tube was added (3R)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin- 4-yl)-lH-pyrazol-l-yl]propanenitrile (153.5 mg) and phosphoric acid (56.6 mg) followed by isopropyl alcohol (IPA) (5.75 mL). The resulting mixture was heated to clear, cooled to room temperature, and then stirred for another 2 hours. The precipitate was collected by filtration and the cake was washed with 0.6 mL of cold IPA. The cake was dried under vacuum to constant weight to provide the final salt product (171.7 mg).
6.4 g With phosphoric acid; In isopropyl alcohol; at 25 - 75℃; A mixture of (i?)-3-(4-(7H-pyrrolo[2,3-ii|pyrimidin-4-yl)-lH-pyrazol-l-yl)-3- cyclopentylpropanenitrile (Formula V, as prepared in Example 4) and isopropyl alcohol (84 mL) was heated to 60C to 65C for 10 minutes to 15 minutes. A solution of phosphoric acid (2.1 g dissolved in 16.8 mL isopropyl alcohol) was added drop-wise to the reaction mixture at 60C to 65C. The reaction mixture was heated to 75C and stirred for 1 hour at the same temperature. The reaction mixture was cooled to 25C over 1.5 hours to 2 hours. The slurry obtained was stirred at 20C to 25 C for 15 hours. The solid obtained was filtered, washed with isopropyl alcohol (12 mL), and then dried under reduced pressure at 40C to 45C to obtain the title compound. (0241) Yield: 6.4 g (0242) Chiral purity: 99.96% (0243) Chromatographic purity: 99.93 %
171.7 mg With phosphoric acid; In isopropyl alcohol; at 20℃; for 2h; <strong>[941678-49-5]Ruxolitinib</strong> prepared according to the steps above, or any other procedure, may be used as its free base for the compositions and methods described heren. <strong>[941678-49-5]Ruxolitinib</strong> may also be used in a salt form. For example, a crystalline phosphoric acid salt of (R)-3-(4-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile may be prepared from the free base as follows according to the procedure given in Example 2 of U.S. Patent No.8,722,693, the disclosure of which is specifically incorporated herein by reference. To a test tube was added <strong>[941678-49-5](R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile</strong> (153.5 mg) and phosphoric acid (56.6 mg) followed by isopropyl alcohol (IPA) (5.75 mL). The resulting mixture was heated to clear, cooled to room temperature, and then stirred for another 2 hours. The precipitate was collected by filtration and the cake was washed with 0.6 mL of cold IPA. The cake was dried under vacuum to constant weight to provide the final salt product (171.7 mg). The phosphroic acid salt is a 1:1 salt by 1H NMR and crystallinity is confirmed by X-ray powder diffraction (XRPD). Differential scanning calorimetry (DSC) of the produce yields a sharp melting peak at about 198.7 C.
171.7 mg With phosphoric acid; In isopropyl alcohol; at 20℃; for 2h;Heating; <strong>[941678-49-5]Ruxolitinib</strong> prepared according to the steps above, or any other procedure, may be used as its free base for the compositions and methods described heren. <strong>[941678-49-5]Ruxolitinib</strong> may also be used in a salt form. For example, a crystalline phosphoric acid salt of (R)-3-(4-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile may be prepared from the free base as follows according to the procedure given in Example 2 of U.S. Patent No.8,722,693, the disclosure of which is specifically incorporated herein by reference. To a test tube was added <strong>[941678-49-5](R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile</strong> (153.5 mg) and phosphoric acid (56.6 mg) followed by isopropyl alcohol (IPA) (5.75 mL). The resulting mixture was heated to clear, cooled to room temperature, and then stirred for another 2 hours. The precipitate was collected by filtration and the cake was washed with 0.6 mL of cold IPA. The cake was dried under vacuum to constant weight to provide the final salt product (171.7 mg). The phosphroic acid salt is a 1:1 salt by 1H NMR and crystallinity is confirmed by X-ray powder diffraction (XRPD). Differential scanning calorimetry (DSC) of the produce yields a sharp melting peak at about 198.7 C.
171.7 mg With phosphoric acid; In isopropyl alcohol; at 20℃; for 2h;Heating; To a test tube was added <strong>[941678-49-5](R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile</strong>(153.5 mg) and phosphoric acid (56.6 mg) followed by isopropyl alcohol (IPA) (5.75 mL). The resulting mixture washeated to clear, cooled to room temperature, and then stirred for another 2 hours. The precipitate was collected byfiltration and the cake was washed with 0.6 mL of cold IPA. The cake was dried under vacuum to constant weight toprovide the final salt product (171.7 mg).The phosphoric acid salt was shown to be a 1:1 salt by 1H NMR and crystallinity was confirmed by X-ray powderdiffraction (XRPD). Differential scanning calorimetry (DSC) gave a sharp melting peak at about 198.66 C. The productshowed little weight loss up to 200 C by TGA
With phosphoric acid; In isopropyl alcohol; at 20℃; for 3h; The (3R)-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propionitrile prepared according to Example 10 was weighed. Crude product,Soluble in isopropanol (20 volumes), to which was added dropwise a solution of isopropanol phosphoric acid (1.1 eq), the mixture was stirred at room temperature for 3 h,During the period, a large amount of white solids gradually precipitated, and the feed liquid was cooled in an ice bath to 5 to 10 C., stirred for 0.5 h, filtered, and dried.Obtain white solid (3R)-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propionitrile phosphate (yield: 90% ), the purity is higher than 99%.

Reference： [1]Patent: US2010/190981,2010,A1 .Location in patent: Page/Page column 80
[2]Patent: US2008/312259,2008,A1 .Location in patent: Page/Page column 6
[3]Patent: WO2013/23119,2013,A1 .Location in patent: Page/Page column 33
[4]Patent: WO2016/35014,2016,A1 .Location in patent: Page/Page column 29
[5]Patent: WO2016/24232,2016,A1 .Location in patent: Paragraph 00676
[6]Patent: WO2016/24230,2016,A1 .Location in patent: Paragraph 00651
[7]Patent: EP2574168,2016,B1 .Location in patent: Paragraph 0151-0153
[8]Patent: CN107759623,2018,A .Location in patent: Paragraph 0118; 0119
  • 2
  • [ 941685-27-4 ]
  • [ 1092939-17-7 ]
Reference： [1]Patent: WO2013/23119,2013,A1
[2]Patent: WO2016/24232,2016,A1
[3]Patent: WO2016/24230,2016,A1
[4]Patent: US9358229,2016,B2
  • 3
  • [ 591769-05-0 ]
  • [ 1092939-17-7 ]
Reference： [1]Patent: WO2013/23119,2013,A1
[2]Patent: WO2016/24232,2016,A1
[3]Patent: WO2016/24230,2016,A1
[4]Patent: US9358229,2016,B2
  • 4
  • [ 941685-39-8 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ethanol; hexane / Resolution of racemate 2: trifluoroacetic acid / dichloromethane / 6 h 3: phosphoric acid / isopropyl alcohol / 20 °C / Heating
Multi-step reaction with 3 steps 1: Resolution of racemate 2: trifluoroacetic acid / dichloromethane / 6 h 3: phosphoric acid / isopropyl alcohol / 2 h / 20 °C
Multi-step reaction with 3 steps 1: Resolution of racemate 2: trifluoroacetic acid / dichloromethane / 6 h 3: phosphoric acid / isopropyl alcohol / 2 h / 20 °C / Heating
Multi-step reaction with 2 steps 1: OD-H / ethanol; hexane / Resolution of racemate 2: phosphoric acid / isopropyl alcohol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: NOVARTIS AG; INCYTE CORP; Novartis (w/o Sandoz) - WO2013/23119, 2013, A1
[2]Current Patent Assignee: ASTRAZENECA PLC - WO2016/24232, 2016, A1
[3]Current Patent Assignee: ASTRAZENECA PLC - WO2016/24230, 2016, A1
[4]Current Patent Assignee: NOVARTIS AG; INCYTE CORP; Novartis (w/o Sandoz) - US9358229, 2016, B2
  • 5
  • [ 941685-40-1 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
95% With phosphoric acid In propan-2-one at 55 - 60℃; 11-12 Example 11 (R)-3-(4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylacrylonitrile phosphate (Compound 9 ) preparationSeveral (R)-3-cyclopentyl-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d] Pyrimidine-4-yl)-1H-pyrazol-1-yl)propionitrile was added to 18 times the volume of acetone,Stir to dissolve.20~30,Phosphoric acid (1.4eq) was added dropwise to it2 volumes of acetone solution.After adding, the temperature was raised to 55~60°C and stirred for 1~2h,Cool to 20~30 and stir for 2h,filter,The filter cake was washed with an appropriate amount of acetone.Blow dry at 40~45 to obtain (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentan Acrylonitrile Phosphate,Yield 95%,Optical purity ≥99.8%, chemical purity ≥99.7%.
Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 6 h 2: phosphoric acid / isopropanol / 20 °C / Heating
Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 6 h 2: phosphoric acid / isopropanol / 2 h / 20 °C
Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 6 h 2: phosphoric acid / isopropanol / 2 h / 20 °C / Heating
17.7 mg With phosphoric acid In isopropanol at 20℃; for 2h; Synthesis of (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2, 3-d]pyrimidin-4-yl)-1 H-pyrazol- 1 -yl]propanenitrilephosphoric acid salt To a test tube was added (3R)-3-Cyclopentyl-3-[4-(7H- pyrrolo[2,3-d]pyrimidin-4-yl)- 1H-pyrazol-1 -yl]propanenitrile (153.5 mg) and phosphoric acid (56.6 mg) followed by isopropyl alcohol (IPA) (5.75 mE). The resulting mixture was heated to clear, cooled to room temperature, and then stirred for another 2 hours. The precipitate was collected by filtration and the cake was washed with 0.6 mE of cold IPA. The cake was dried under vacuum to constant weight to provide the final salt product (171.7 mg).

Reference： [1]Current Patent Assignee: NANJING BAIMAI BIOTECHNOLOGY CO LTD - CN114044777, 2022, A Location in patent: Paragraph 0010; 0049-0053
[2]Current Patent Assignee: NOVARTIS AG; INCYTE CORP; Novartis (w/o Sandoz) - WO2013/23119, 2013, A1
[3]Current Patent Assignee: ASTRAZENECA PLC - WO2016/24232, 2016, A1
[4]Current Patent Assignee: ASTRAZENECA PLC - WO2016/24230, 2016, A1
[5]Current Patent Assignee: NOVARTIS AG; INCYTE CORP; Novartis (w/o Sandoz) - US9358229, 2016, B2 Location in patent: Page/Page column 23
  • 6
  • [ 941688-05-7 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: acetonitrile / 20 - 70 °C 2: sodium hydroxide / water; ethyl acetate / 20 - 25 °C / pH 9.5 - 10 3: phosphoric acid / isopropyl alcohol / 25 - 75 °C
Reference： [1]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2016/35014, 2016, A1
  • 7
  • [ 941678-49-5 ]
  • (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile phosphoric acid salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
95% With phosphoric acid; In water; ethyl acetate; at 50℃; for 1h; 2 g (6.528 mmol) of <strong>[941678-49-5]ruxolitinib</strong> free base was suspended in 10 mL of ethyl-acetate by heating to 50C applying a continuous stirring.0.4 mL of phosphoric acid (6.528 mmol; 85% aqueous solution) was drop-wise added to the suspension of <strong>[941678-49-5]ruxolitinib</strong> at 50C, while continuously stirred. The suspension was stirred at this temperature for 1 hour then placed onto ice to cool. The solid obtained was filtered off and dried at laboratory condition.Product: 2.506 g (6.19 mmol) off-white crystalline solid Yield: 95% HPLC: 99.8% XRPD pattern was measured (Figure 6) and showed that the compound is in a crystalline state that was designated as Crystal modification 1 of <strong>[941678-49-5]ruxolitinib</strong> phosphoric acid salt. 1H-NMR spectrum was measured (Figure 11) and showed that the compound confirms the structure with an API : phosphoric acid stoichiometry of 1:1.
Reference： [1]Patent: WO2017/125097,2017,A1 .Location in patent: Page/Page column 26; 27
  • 8
  • C17H24ClN3O5 [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / tetrahydrofuran; water / 50 - 60 °C / Inert atmosphere 2: hydrogenchloride / tetrahydrofuran; water / 20 °C / Reflux 3: phosphoric acid / isopropyl alcohol / 3 h / 20 °C
Reference： [1]Current Patent Assignee: SUZHOU WANGSHAN WANGSHUI BIOMEDICAL CO LTD - CN107759623, 2018, A
  • 9
  • C28H38N6O5 [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydrogenchloride / tetrahydrofuran; water / 20 °C / Reflux 2: phosphoric acid / isopropyl alcohol / 3 h / 20 °C
Reference： [1]Current Patent Assignee: SUZHOU WANGSHAN WANGSHUI BIOMEDICAL CO LTD - CN107759623, 2018, A
  • 10
  • [ 5305-40-8 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: ammonia / toluene; methanol / 2 h / 60 °C 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 1 h / -5 - 0 °C / Inert atmosphere 2.2: 30 h / 20 °C / Inert atmosphere 3.1: dmap / ethyl acetate / 2 h / 45 - 50 °C 4.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / tetrahydrofuran; water / 50 - 60 °C / Inert atmosphere 5.1: hydrogenchloride / tetrahydrofuran; water / 20 °C / Reflux 6.1: phosphoric acid / isopropyl alcohol / 3 h / 20 °C
Reference： [1]Current Patent Assignee: SUZHOU WANGSHAN WANGSHUI BIOMEDICAL CO LTD - CN107759623, 2018, A
  • 11
  • [ 137-43-9 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 11 steps 1.1: magnesium; iodine / tetrahydrofuran / 30 - 40 °C / Inert atmosphere 1.2: 1 h / 10 - 30 °C / Inert atmosphere 2.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0 °C / Inert atmosphere 2.2: 0 - 30 °C / Inert atmosphere 3.1: acetonitrile / 30 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 30 °C 5.1: (1S,2R)-1-amino-2-indanol / isopropyl alcohol / 20 °C 6.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 3 h / 20 °C / Inert atmosphere 6.2: 0.5 h 7.1: phosphorus pentoxide / tetrahydrofuran / 60 - 70 °C / Inert atmosphere 8.1: isopropylmagnesium chloride / tetrahydrofuran / 1 h / -15 - 5 °C / Inert atmosphere 8.2: -5 - 5 °C / Inert atmosphere 9.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / tetrahydrofuran; water / 50 - 60 °C / Inert atmosphere 10.1: hydrogenchloride / tetrahydrofuran; water / 20 °C / Reflux 11.1: phosphoric acid / isopropyl alcohol / 3 h / 20 °C
Reference： [1]Current Patent Assignee: SUZHOU WANGSHAN WANGSHUI BIOMEDICAL CO LTD - CN107759623, 2018, A
  • 12
  • [ 14160-93-1 ]
  • [ 1092939-17-7 ]
Reference： [1]Patent: CN107759623,2018,A
  • 13
  • 6-chloro-5-(2-methoxyvinyl)pyrimidin-4-ylamine [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 4-dimethylaminopyridine / ethyl acetate / 2 h / 45 - 50 °C 2: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / tetrahydrofuran; water monomer / 50 - 60 °C / Inert atmosphere 3: hydrogenchloride / tetrahydrofuran; water monomer / 20 °C / Reflux 4: phosphoric acid / isopropanol / 3 h / 20 °C
Multi-step reaction with 7 steps 1.1: hydrogenchloride / water monomer; tetrahydrofuran / 7.5 h / Reflux 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 2.2: 0 - 15 °C / Large scale 3.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 4.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 5.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 5.2: 21.5 h / 20 - 50 °C 6.1: ethanol; water monomer / 20 °C 7.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 8 steps 1.1: hydrogenchloride / water monomer; tetrahydrofuran / 7.5 h / Reflux 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 2.2: 0 - 15 °C / Large scale 3.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 4.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 5.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 5.2: 21.5 h / 20 - 50 °C 6.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 7.1: ethanol / 5 h / 20 °C 8.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 8 steps 1.1: hydrogenchloride / water monomer; tetrahydrofuran / 7.5 h / Reflux 2.1: sodium hydroxide / water monomer; propan-2-one / 1 h / 20 °C 3.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 4.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 5.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 6.1: trichlorophosphate / 0.5 h / 80 - 90 °C 6.2: pH 7 - 8 6.3: 2 h / 0 - 20 °C 7.1: ethanol / 5 h / 20 °C 8.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 8 steps 1.1: hydrogenchloride / water monomer; tetrahydrofuran / 7.5 h / Reflux 2.1: sodium hydroxide / water monomer; propan-2-one / 1 h / 20 °C 3.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 4.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 5.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 6.1: trichlorophosphate / 0.5 h / 80 - 90 °C 6.2: pH 7 - 8 6.3: 2 h / 0 - 20 °C 7.1: ethanol / 5 h / 20 °C 8.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 8 steps 1.1: hydrogenchloride / water monomer; tetrahydrofuran / 7.5 h / Reflux 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 2.2: 0 - 15 °C / Large scale 3.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 4.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 5.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 5.2: 21.5 h / 20 - 50 °C 6.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 7.1: N,N-dimethyl-formamide / 22 h / 20 °C 8.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C

Reference： [1]Current Patent Assignee: SUZHOU WANGSHAN WANGSHUI BIOMEDICAL CO LTD - CN107759623, 2018, A
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[4]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[5]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[6]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 14
  • [ 872-53-7 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0 °C / Inert atmosphere 1.2: 0 - 30 °C / Inert atmosphere 2.1: acetonitrile / 30 °C 3.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 30 °C 4.1: (1S,2R)-1-amino-2-indanol / isopropyl alcohol / 20 °C 5.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 3 h / 20 °C / Inert atmosphere 5.2: 0.5 h 6.1: phosphorus pentoxide / tetrahydrofuran / 60 - 70 °C / Inert atmosphere 7.1: isopropylmagnesium chloride / tetrahydrofuran / 1 h / -15 - 5 °C / Inert atmosphere 7.2: -5 - 5 °C / Inert atmosphere 8.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / tetrahydrofuran; water / 50 - 60 °C / Inert atmosphere 9.1: hydrogenchloride / tetrahydrofuran; water / 20 °C / Reflux 10.1: phosphoric acid / isopropyl alcohol / 3 h / 20 °C
Reference： [1]Current Patent Assignee: SUZHOU WANGSHAN WANGSHUI BIOMEDICAL CO LTD - CN107759623, 2018, A
  • 15
  • [ 136823-41-1 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: acetonitrile / 30 °C 2.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 30 °C 3.1: (1S,2R)-1-amino-2-indanol / isopropyl alcohol / 20 °C 4.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 3 h / 20 °C / Inert atmosphere 4.2: 0.5 h 5.1: phosphorus pentoxide / tetrahydrofuran / 60 - 70 °C / Inert atmosphere 6.1: isopropylmagnesium chloride / tetrahydrofuran / 1 h / -15 - 5 °C / Inert atmosphere 6.2: -5 - 5 °C / Inert atmosphere 7.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / tetrahydrofuran; water / 50 - 60 °C / Inert atmosphere 8.1: hydrogenchloride / tetrahydrofuran; water / 20 °C / Reflux 9.1: phosphoric acid / isopropyl alcohol / 3 h / 20 °C
Reference： [1]Current Patent Assignee: SUZHOU WANGSHAN WANGSHUI BIOMEDICAL CO LTD - CN107759623, 2018, A
  • 16
  • methyl 3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropionate [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 30 °C 2.1: (1S,2R)-1-amino-2-indanol / isopropyl alcohol / 20 °C 3.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 3 h / 20 °C / Inert atmosphere 3.2: 0.5 h 4.1: phosphorus pentoxide / tetrahydrofuran / 60 - 70 °C / Inert atmosphere 5.1: isopropylmagnesium chloride / tetrahydrofuran / 1 h / -15 - 5 °C / Inert atmosphere 5.2: -5 - 5 °C / Inert atmosphere 6.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / tetrahydrofuran; water / 50 - 60 °C / Inert atmosphere 7.1: hydrogenchloride / tetrahydrofuran; water / 20 °C / Reflux 8.1: phosphoric acid / isopropyl alcohol / 3 h / 20 °C
Reference： [1]Current Patent Assignee: SUZHOU WANGSHAN WANGSHUI BIOMEDICAL CO LTD - CN107759623, 2018, A
  • 17
  • 3-(4-bromo-1H-pyrazol-1-yl)-3-cyclopentylpropionic acid [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: (1S,2R)-1-amino-2-indanol / isopropyl alcohol / 20 °C 2.1: 1,1'-carbonyldiimidazole / tetrahydrofuran / 3 h / 20 °C / Inert atmosphere 2.2: 0.5 h 3.1: phosphorus pentoxide / tetrahydrofuran / 60 - 70 °C / Inert atmosphere 4.1: isopropylmagnesium chloride / tetrahydrofuran / 1 h / -15 - 5 °C / Inert atmosphere 4.2: -5 - 5 °C / Inert atmosphere 5.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / tetrahydrofuran; water / 50 - 60 °C / Inert atmosphere 6.1: hydrogenchloride / tetrahydrofuran; water / 20 °C / Reflux 7.1: phosphoric acid / isopropyl alcohol / 3 h / 20 °C
Reference： [1]Current Patent Assignee: SUZHOU WANGSHAN WANGSHUI BIOMEDICAL CO LTD - CN107759623, 2018, A
  • 18
  • C9H10F3NO3S [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate / 13 h 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 3 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 3 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 2: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 4 steps 1.1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 23 °C 2.1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 17 h / 23 °C / 7500.75 Torr / Sealed tube 3.1: trifluoroacetic acid / toluene / 0.25 h / 100 °C 3.2: 0.25 h / 40 °C 4.1: isopropanol
Multi-step reaction with 4 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 3: phosphoric acid / isopropanol; dichloromethane / 20 °C 4: isopropanol
Multi-step reaction with 4 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 3: phosphoric acid / isopropanol; dichloromethane / 20 °C 4: isopropanol
Multi-step reaction with 4 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 2: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 4: isopropanol
Multi-step reaction with 4 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 4: isopropanol

Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[3]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[4]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[5]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[6]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[7]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[8]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 19
  • [ 16019-33-3 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: toluene-4-sulfonic acid / methanol / 1.5 h / 40 °C 2: ammonium hydroxide / isopropanol / 8 h / 70 °C 3: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 20 - 90 °C / Inert atmosphere 4: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate / 13 h 5: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 6: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 6 steps 1: toluene-4-sulfonic acid / methanol / 1.5 h / 40 °C 2: ammonium hydroxide / isopropanol / 8 h / 70 °C 3: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 4: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 5: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 6: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 6 steps 1: toluene-4-sulfonic acid / methanol / 1.5 h / 40 °C 2: ammonium hydroxide / isopropanol / 8 h / 70 °C 3: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 4: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 5: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 6: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 7 steps 1: toluene-4-sulfonic acid / methanol / 1.5 h / 40 °C 2: ammonium hydroxide / isopropanol / 8 h / 70 °C 3: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 4: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 5: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 6: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 7: isopropanol
Multi-step reaction with 7 steps 1: toluene-4-sulfonic acid / methanol / 1.5 h / 40 °C 2: ammonium hydroxide / isopropanol / 8 h / 70 °C 3: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 4: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 5: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 6: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 7: isopropanol
Multi-step reaction with 8 steps 1.1: toluene-4-sulfonic acid / methanol / 1.5 h / 40 °C 2.1: ammonium hydroxide / isopropanol / 8 h / 70 °C 3.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 0.5 h / 0 °C 3.2: 8 h / 0 - 20 °C 4.1: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / lithium hydroxide monohydrate; tetrahydrofuran / 60 °C 5.1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 23 °C 6.1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 17 h / 23 °C / 7500.75 Torr / Sealed tube 7.1: trifluoroacetic acid / toluene / 0.25 h / 100 °C 7.2: 0.25 h / 40 °C 8.1: isopropanol
Multi-step reaction with 8 steps 1: toluene-4-sulfonic acid / methanol / 1.5 h / 40 °C 2: ammonium hydroxide / isopropanol / 8 h / 70 °C 3: triethylamine; 4-dimethylaminopyridine / dichloromethane / 62 h / 0 - 23 °C 4: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 90 °C / Inert atmosphere 5: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 6: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 7: phosphoric acid / isopropanol; dichloromethane / 20 °C 8: isopropanol
Multi-step reaction with 8 steps 1: toluene-4-sulfonic acid / methanol / 1.5 h / 40 °C 2: ammonium hydroxide / isopropanol / 8 h / 70 °C 3: triethylamine; 4-dimethylaminopyridine / dichloromethane / 62 h / 0 - 23 °C 4: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 90 °C / Inert atmosphere 5: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 6: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 7: phosphoric acid / isopropanol; dichloromethane / 20 °C 8: isopropanol

Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[3]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[4]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[5]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[6]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[7]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[8]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 20
  • 4,6-dichloro-5-(2,2-dimethoxyethyl)pyrimidine [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: ammonium hydroxide / isopropanol / 8 h / 70 °C 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 20 - 90 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate / 13 h 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 5 steps 1: ammonium hydroxide / isopropanol / 8 h / 70 °C 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 5 steps 1: ammonium hydroxide / isopropanol / 8 h / 70 °C 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 6 steps 1: ammonium hydroxide / isopropanol / 8 h / 70 °C 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 6: isopropanol
Multi-step reaction with 6 steps 1: ammonium hydroxide / isopropanol / 8 h / 70 °C 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 6: isopropanol
Multi-step reaction with 7 steps 1.1: ammonium hydroxide / isopropanol / 8 h / 70 °C 2.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 0.5 h / 0 °C 2.2: 8 h / 0 - 20 °C 3.1: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / lithium hydroxide monohydrate; tetrahydrofuran / 60 °C 4.1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 23 °C 5.1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 17 h / 23 °C / 7500.75 Torr / Sealed tube 6.1: trifluoroacetic acid / toluene / 0.25 h / 100 °C 6.2: 0.25 h / 40 °C 7.1: isopropanol
Multi-step reaction with 7 steps 1: ammonium hydroxide / isopropanol / 8 h / 70 °C 2: triethylamine; 4-dimethylaminopyridine / dichloromethane / 62 h / 0 - 23 °C 3: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 90 °C / Inert atmosphere 4: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 5: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 6: phosphoric acid / isopropanol; dichloromethane / 20 °C 7: isopropanol
Multi-step reaction with 7 steps 1: ammonium hydroxide / isopropanol / 8 h / 70 °C 2: triethylamine; 4-dimethylaminopyridine / dichloromethane / 62 h / 0 - 23 °C 3: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 90 °C / Inert atmosphere 4: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 5: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 6: phosphoric acid / isopropanol; dichloromethane / 20 °C 7: isopropanol

Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[3]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[4]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[5]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[6]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[7]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[8]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 21
  • 6-chloro-5-(2,2-dimethoxyethyl)pyrimidin-4-amine [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 20 - 90 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate / 13 h 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 4 steps 1: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 3: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 4 steps 1: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 5 steps 1: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 5: isopropanol
Multi-step reaction with 5 steps 1: potassium carbonate; tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl[2’,4’,6’-tris(propan-2-yl)[1,1’-biphenyl]-2-yl]phosphane / 1,4-dioxane; lithium hydroxide monohydrate / 3 h / 90 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 3: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 5: isopropanol
Multi-step reaction with 6 steps 1.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / 0.5 h / 0 °C 1.2: 8 h / 0 - 20 °C 2.1: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / lithium hydroxide monohydrate; tetrahydrofuran / 60 °C 3.1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 23 °C 4.1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 17 h / 23 °C / 7500.75 Torr / Sealed tube 5.1: trifluoroacetic acid / toluene / 0.25 h / 100 °C 5.2: 0.25 h / 40 °C 6.1: isopropanol
Multi-step reaction with 6 steps 1: triethylamine; 4-dimethylaminopyridine / dichloromethane / 62 h / 0 - 23 °C 2: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 90 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 5: phosphoric acid / isopropanol; dichloromethane / 20 °C 6: isopropanol
Multi-step reaction with 6 steps 1: triethylamine; 4-dimethylaminopyridine / dichloromethane / 62 h / 0 - 23 °C 2: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 90 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 5: phosphoric acid / isopropanol; dichloromethane / 20 °C 6: isopropanol

Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[3]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[4]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[5]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[6]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[7]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[8]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 22
  • 5-(2,2-dimethoxyethyl)-6-(1H-pyrazol-4-yl)pyrimidin-4-amine [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate / 13 h 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 3 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 3 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 2: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 4 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 2: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 4: isopropanol
Multi-step reaction with 4 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 3: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 4: isopropanol

Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[3]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[4]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[5]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 23
  • (Z)-3-(4-(6-amino-5-(2,2-dimethoxyethyl)pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylacrylonitrile [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 2: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 2 steps 1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 2: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 2 steps 1: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 2: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 3 steps 1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 2: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 3: isopropanol
Multi-step reaction with 3 steps 1: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 2: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 3: isopropanol

Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[3]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[4]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[5]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 24
  • [ 4630-80-2 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -3 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate / 13 h 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 5 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 5 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 6 steps 1.1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2.1: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3.1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 23 °C 4.1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 17 h / 23 °C / 7500.75 Torr / Sealed tube 5.1: trifluoroacetic acid / toluene / 0.25 h / 100 °C 5.2: 0.25 h / 40 °C 6.1: isopropanol
Multi-step reaction with 6 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 5: phosphoric acid / isopropanol; dichloromethane / 20 °C 6: isopropanol
Multi-step reaction with 6 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 5: phosphoric acid / isopropanol; dichloromethane / 20 °C 6: isopropanol
Multi-step reaction with 6 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 6: isopropanol
Multi-step reaction with 6 steps 1: sodium bis-(trimethyl-silyl)amide / tetrahydrofuran / -14.6 - 24 °C / Inert atmosphere 2: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 3: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 4: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 5: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 6: isopropanol

Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[3]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[4]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[5]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[6]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[7]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[8]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 25
  • [ 95882-33-0 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 4-methyl-morpholine / toluene / 0 - 5 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate / 13 h 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 4 steps 1: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 4 steps 1: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 3: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; phosphoric acid
Multi-step reaction with 5 steps 1.1: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 2.1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 23 °C 3.1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 17 h / 23 °C / 7500.75 Torr / Sealed tube 4.1: trifluoroacetic acid / toluene / 0.25 h / 100 °C 4.2: 0.25 h / 40 °C 5.1: isopropanol
Multi-step reaction with 5 steps 1: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 4: phosphoric acid / isopropanol; dichloromethane / 20 °C 5: isopropanol
Multi-step reaction with 5 steps 1: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 4: phosphoric acid / isopropanol; dichloromethane / 20 °C 5: isopropanol
Multi-step reaction with 5 steps 1: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 3: hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 20 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 5: isopropanol
Multi-step reaction with 5 steps 1: 4-methyl-morpholine / toluene / 0 h / 0 - 5 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 13 h / 0 - 23 °C 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / 2,2,2-trifluoroethanol / 17 h / 23 °C / 7500.75 Torr / Sealed tube 4: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 5: isopropanol

Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[3]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[4]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[5]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[6]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[7]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[8]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 26
  • (R)-3-(4-(6-amino-5-(2,2-dimethoxyethyl)pyrimidin-4-yl)-1H- pyrazol-1-yl)-3-cyclopentylpropanenitrile [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
With phosphoric acid; trifluoroacetic acid
Multi-step reaction with 2 steps 1: trifluoroacetic acid; trifluoroacetic anhydride / toluene / 1 h / 100 °C 2: isopropanol
Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1 Location in patent: Paragraph 205
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 27
  • [ 479633-63-1 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; water monomer / 4 h / 80 °C / Inert atmosphere 2.1: acetonitrile / 60 °C 3.1: sodium hydroxide / water monomer; methanol / 2 h / 20 °C 3.2: 1 h
Multi-step reaction with 6 steps 1: Cs2CO3 2: potassium etoxide 3: sodium hydroxide 4: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 6 steps 1: Cs2CO3 2: potassium etoxide 3: sodium hydroxide 4: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 6 steps 1.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 2.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 3.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 4.1: trichlorophosphate / 0.5 h / 80 - 90 °C 4.2: pH 7 - 8 4.3: 2 h / 0 - 20 °C 5.1: ethanol / 5 h / 20 °C 6.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 6 steps 1.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 2.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 3.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 4.1: trichlorophosphate / 0.5 h / 80 - 90 °C 4.2: pH 7 - 8 4.3: 2 h / 0 - 20 °C 5.1: ethanol / 5 h / 20 °C 6.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C

Reference： [1]Current Patent Assignee: CHANGZHOU PHARMACEUTICAL FACTORY CO., LTD. - CN113292569, 2021, A
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[4]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[5]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 28
  • [ 1153949-38-2 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: potassium carbonate; tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 4 h / 80 °C / Inert atmosphere 2.1: acetonitrile / 60 °C 3.1: sodium hydroxide / water; methanol / 2 h / 20 °C 3.2: 1 h
Reference： [1]Current Patent Assignee: CHANGZHOU PHARMACEUTICAL FACTORY CO., LTD. - CN113292569, 2021, A
  • 29
  • (R)-3-cyclopentyl-3-(4-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile dibenzoyltartaric acid [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: (R)-3-cyclopentyl-3-(4-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)propanenitrile dibenzoyltartaric acid With sodium hydroxide In methanol; water at 20℃; for 2h; Stage #2: With phosphoric acid In methanol; water; isopropyl alcohol for 1h; 1.3 3.(R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile (compound 1)Preparation Compound 5 (10g, 12.2mmol, 1eq) was dissolved in 100ml methanol, 1N sodium hydroxide aq (24.4ml, 24.4mmol, 2eq) was added at room temperature, and after addition, stirred at room temperature for 2h. TLC detects the completion of the reaction, adds 100 ml of dichloromethane and 100 ml of water, stirs and separates the layers, the aqueous layer is extracted with dichloromethane (50 ml), the organic layers are combined, and dried over anhydrous sodium sulfate. Suction filtration, dropwise add 85% phosphoric acid (1.4g, 12.2mmol, 1eq) in isopropanol (15ml) solution to the filtrate, solids precipitate out, stir for 1h, suction filtration, and dry at 50 to obtain white solid target compound 1 (yield 90.0%). The HPLC purity is 99.9%, and the ee value is 99.8%.
Reference： [1]Current Patent Assignee: CHANGZHOU PHARMACEUTICAL FACTORY CO., LTD. - CN113292569, 2021, A Location in patent: Paragraph 0017; 0036; 0041-0042
  • 30
  • (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)allylidene)-N-methylmethanaminium chloride [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: anhydrous sodium perchlorate
Multi-step reaction with 3 steps 1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 2: ethanol / 5 h / 20 °C 3: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 3 steps 1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 2: N,N-dimethyl-formamide / 22 h / 20 °C 3: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 31
  • [ 941678-49-5 ]
  • [ 67-63-0 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
13 (3R)-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propionitrilephosphate (Compound 1 Phosphate) (3R)-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propionitrilephosphate (Compound 1 Phosphate) A suspension of the crude Compound 1 phosphate (40.0 g, 100 mmol) in methanol (MeOH, 520 mL) is heated to 50-60° C. to generate a homogenous solution. The solution is polish filtered at 50-60° C. Methanol (287 mL) is partially distilled at atmosphere pressure at 60-70° C. before IPA (320 mL) is added to the mixture at the same temperature to initiate crystallization of the final product (Compound 1 phosphate). n-Heptane (1000 mL) is then added to the mixture at 60-70° C. and the distillation is continued at atmospheric pressure at 60-70° C. Once the distillation is complete, the mixture is stirred at 60-70° C. for 10-60 minutes before being gradually cooled to room temperature and stirred at room temperature for 3-6 hours. The solids are collected by filtration, washed sequentially with a mixture of IPA and n-heptane and n-heptane, and dried at 40-50° C. under vacuum to afford the final product, (Compound 1 phosphate, 39.4 g, 98.5%) as white crystalline powders. For Compound 1 phosphate mp. 197.6° C.; 1H NMR (DMSO-d6, 500 MHz) δ ppm 12.10 (s, 1H), 8.78 (s, 1H), 8.68 (s, 1H), 8.36 (s 1H), 7.58 (dd, 1H, J=1.9, 3.5 Hz), 6.97 (d, 1H, J=3.6 Hz), 4.52 (td, 1H, J=3.9, 9.7 Hz), 3.25 (dd, 1H, J=9.8, 17.2 Hz), 3.16 (dd, 1H, J=4.0, 17.0 Hz), 2.41, (m, 1H), 1.79 (m, 1H), 1.59 (m, 1H), 1.51 (m, 2H), 1.42 (m, 1H), 1.29 (m, 2H), 1.18 (m, 1H); 13C NMR (DMSO-d6, 125 MHz) δ ppm 152.1, 150.8, 149.8, 139.2, 131.0, 126.8, 120.4, 118.1, 112.8, 99.8, 62.5, 44.3, 29.1, 29.0, 24.9, 24.3, 22.5; C17H18N6 (MW, 306.37 for free base) LCMS (EI) m/e 307 (M++H, base peak), 329.1 (M++Na).
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 32
  • (E)-N-(3-(dimethylamino)-2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)allylidene)-N-methylmethanaminium perchlorate [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: ethanol / 5 h / 20 °C 2: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 33
  • [ 945950-37-8 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: anhydrous sodium perchlorate
Multi-step reaction with 3 steps 1.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: ethanol; water monomer / 20 °C 3.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 4 steps 1.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 3.1: N,N-dimethyl-formamide / 22 h / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 4 steps 1.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 1.2: 21.5 h / 20 - 50 °C 2.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 3.1: ethanol / 5 h / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[4]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 34
  • 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetic acid [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 3 steps 1.1: trichlorophosphate / 0.5 h / 80 - 90 °C 1.2: pH 7 - 8 1.3: 2 h / 0 - 20 °C 2.1: ethanol / 5 h / 20 °C 3.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 35
  • sodium 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 3 steps 1.1: trichlorophosphate / 0.5 h / 80 - 90 °C 1.2: pH 7 - 8 1.3: 2 h / 0 - 20 °C 2.1: ethanol / 5 h / 20 °C 3.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 36
  • [ 3680-69-1 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 2: Cs2CO3 3: potassium etoxide 4: sodium hydroxide 5: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 7 steps 2: Cs2CO3 3: potassium etoxide 4: sodium hydroxide 5: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 6 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 1.2: 0 - 15 °C / Large scale 2.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 3.1: ammonium hydroxide / methanol; lithium hydroxide monohydrate / 16 h / 15 - 40 °C / Large scale 4.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 4.2: 21.5 h / 20 - 50 °C 5.1: ethanol; lithium hydroxide monohydrate / 20 °C 6.1: phosphoric acid / isopropanol; lithium hydroxide monohydrate; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 7 steps 1.1: sodium hydroxide / lithium hydroxide monohydrate; propan-2-one / 1 h / 20 °C 2.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 3.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 4.1: sodium hydroxide; lithium hydroxide monohydrate / lithium hydroxide monohydrate; tetrahydrofuran; propan-2-one / 5 h / 20 °C 5.1: trichlorophosphate / 0.5 h / 80 - 90 °C 5.2: pH 7 - 8 5.3: 2 h / 0 - 20 °C 6.1: ethanol / 5 h / 20 °C 7.1: phosphoric acid / isopropanol; lithium hydroxide monohydrate; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 7 steps 1.1: sodium hydroxide / lithium hydroxide monohydrate; propan-2-one / 1 h / 20 °C 2.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 3.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 4.1: sodium hydroxide; lithium hydroxide monohydrate / lithium hydroxide monohydrate; tetrahydrofuran; propan-2-one / 5 h / 20 °C 5.1: trichlorophosphate / 0.5 h / 80 - 90 °C 5.2: pH 7 - 8 5.3: 2 h / 0 - 20 °C 6.1: ethanol / 5 h / 20 °C 7.1: phosphoric acid / isopropanol; lithium hydroxide monohydrate; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 7 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 1.2: 0 - 15 °C / Large scale 2.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 3.1: ammonium hydroxide / methanol; lithium hydroxide monohydrate / 16 h / 15 - 40 °C / Large scale 4.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 4.2: 21.5 h / 20 - 50 °C 5.1: anhydrous sodium perchlorate / lithium hydroxide monohydrate / 12 h / 20 - 25 °C 6.1: ethanol / 5 h / 20 °C 7.1: phosphoric acid / isopropanol; lithium hydroxide monohydrate; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 7 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 1.2: 0 - 15 °C / Large scale 2.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 3.1: ammonium hydroxide / methanol; lithium hydroxide monohydrate / 16 h / 15 - 40 °C / Large scale 4.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 4.2: 21.5 h / 20 - 50 °C 5.1: sodium hydroxide / lithium hydroxide monohydrate; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 6.1: N,N-dimethyl-formamide / 22 h / 20 °C 7.1: phosphoric acid / isopropanol; lithium hydroxide monohydrate; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 6 steps 1.1: sodium hydride / -10 - 25 °C / Inert atmosphere 1.2: -5 - 25 °C / Inert atmosphere 2.1: isopropylmagnesium chloride lithium chloride / dimethyl sulfoxide / -10 - 5 °C / Inert atmosphere 2.2: 0 - 5 °C / Inert atmosphere 3.1: bis(tricyclohexylphosphine)nickel(II) dichloride; anhydrous potassium acetate / N,N-dimethyl-formamide; lithium hydroxide monohydrate / 65 - 70 °C / Inert atmosphere 4.1: 4-dimethylaminopyridine / N,N-dimethyl acetamide / 25 - 30 °C 5.1: (+)-cis-1,2,2-trimethyl-1,3-cyclopentanedicarboxylic acid / acetic acid methyl ester / 55 - 60 °C 6.1: phosphoric acid / propan-2-one / 55 - 60 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[4]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[5]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[6]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[7]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[8]Current Patent Assignee: NANJING BAIMAI BIOTECHNOLOGY CO LTD - CN114044777, 2022, A
  • 37
  • [ 52133-67-2 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1: anhydrous ammonium chloride; potassium etoxide; ammonium hydroxide 2: trichlorophosphate 4: Cs2CO3 5: potassium etoxide 6: sodium hydroxide 7: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 9 steps 1: anhydrous ammonium chloride; potassium etoxide; ammonium hydroxide 2: trichlorophosphate 4: Cs2CO3 5: potassium etoxide 6: sodium hydroxide 7: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 10 steps 1.1: potassium etoxide / ethanol / 1 h / 20 °C / Large scale 1.2: 75 °C / Large scale 2.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 3.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 4.1: sodium hydroxide / water monomer; propan-2-one / 1 h / 20 °C 5.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 6.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 7.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 8.1: trichlorophosphate / 0.5 h / 80 - 90 °C 8.2: pH 7 - 8 8.3: 2 h / 0 - 20 °C 9.1: ethanol / 5 h / 20 °C 10.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 10 steps 1.1: potassium etoxide / ethanol / 1 h / 20 °C / Large scale 1.2: 75 °C / Large scale 2.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 3.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 4.1: sodium hydroxide / water monomer; propan-2-one / 1 h / 20 °C 5.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 6.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 7.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 8.1: trichlorophosphate / 0.5 h / 80 - 90 °C 8.2: pH 7 - 8 8.3: 2 h / 0 - 20 °C 9.1: ethanol / 5 h / 20 °C 10.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 10 steps 1.1: potassium etoxide / ethanol / 1 h / 20 °C / Large scale 1.2: 75 °C / Large scale 2.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 3.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 4.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 4.2: 0 - 15 °C / Large scale 5.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 6.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 7.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 7.2: 21.5 h / 20 - 50 °C 8.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 9.1: N,N-dimethyl-formamide / 22 h / 20 °C 10.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 10 steps 1.1: potassium etoxide / ethanol / 1 h / 20 °C / Large scale 1.2: 75 °C / Large scale 2.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 3.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 4.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 4.2: 0 - 15 °C / Large scale 5.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 6.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 7.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 7.2: 21.5 h / 20 - 50 °C 8.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 9.1: ethanol / 5 h / 20 °C 10.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 9 steps 1.1: potassium etoxide / ethanol / 1 h / 20 °C / Large scale 1.2: 75 °C / Large scale 2.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 3.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 4.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 4.2: 0 - 15 °C / Large scale 5.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 6.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 7.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 7.2: 21.5 h / 20 - 50 °C 8.1: ethanol; water monomer / 20 °C 9.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[4]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[5]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[6]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[7]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 38
  • [ 3680-71-5 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1: trichlorophosphate 3: Cs2CO3 4: potassium etoxide 5: sodium hydroxide 6: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 8 steps 1: trichlorophosphate 3: Cs2CO3 4: potassium etoxide 5: sodium hydroxide 6: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 7 steps 1.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 2.2: 0 - 15 °C / Large scale 3.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 4.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 5.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 5.2: 21.5 h / 20 - 50 °C 6.1: ethanol; water monomer / 20 °C 7.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 8 steps 1.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 2.1: sodium hydroxide / water monomer; propan-2-one / 1 h / 20 °C 3.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 4.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 5.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 6.1: trichlorophosphate / 0.5 h / 80 - 90 °C 6.2: pH 7 - 8 6.3: 2 h / 0 - 20 °C 7.1: ethanol / 5 h / 20 °C 8.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 8 steps 1.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 2.1: sodium hydroxide / water monomer; propan-2-one / 1 h / 20 °C 3.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 4.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 5.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 6.1: trichlorophosphate / 0.5 h / 80 - 90 °C 6.2: pH 7 - 8 6.3: 2 h / 0 - 20 °C 7.1: ethanol / 5 h / 20 °C 8.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 8 steps 1.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 2.2: 0 - 15 °C / Large scale 3.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 4.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 5.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 5.2: 21.5 h / 20 - 50 °C 6.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 7.1: ethanol / 5 h / 20 °C 8.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 8 steps 1.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 2.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 2.2: 0 - 15 °C / Large scale 3.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 4.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 5.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 5.2: 21.5 h / 20 - 50 °C 6.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 7.1: N,N-dimethyl-formamide / 22 h / 20 °C 8.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[4]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[5]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[6]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[7]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 39
  • diethyl 2-(7-tosyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)malonate [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: potassium etoxide 2: sodium hydroxide 3: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 5 steps 1: potassium etoxide 2: sodium hydroxide 3: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 5 steps 1.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 2.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 3.1: trichlorophosphate / 0.5 h / 80 - 90 °C 3.2: pH 7 - 8 3.3: 2 h / 0 - 20 °C 4.1: ethanol / 5 h / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 5 steps 1.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 2.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 3.1: trichlorophosphate / 0.5 h / 80 - 90 °C 3.2: pH 7 - 8 3.3: 2 h / 0 - 20 °C 4.1: ethanol / 5 h / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[4]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 40
  • ethyl 2-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)acetate [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: sodium hydroxide 2: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 4 steps 1: sodium hydroxide 2: anhydrous sodium perchlorate; trichlorophosphate
Multi-step reaction with 4 steps 1.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 2.1: trichlorophosphate / 0.5 h / 80 - 90 °C 2.2: pH 7 - 8 2.3: 2 h / 0 - 20 °C 3.1: ethanol / 5 h / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 4 steps 1.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 2.1: trichlorophosphate / 0.5 h / 80 - 90 °C 2.2: pH 7 - 8 2.3: 2 h / 0 - 20 °C 3.1: ethanol / 5 h / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[4]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 41
  • 2-acetyl-4,4-dimethoxybutanenitrile [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: orthoformic acid triethyl ester / tetrahydrofuran; butan-1-ol / 41 h / 110 - 120 °C 2.1: hydrogenchloride / isopropanol; water monomer / 72 h / 20 °C 3.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 3.2: 21.5 h / 20 - 50 °C 4.1: ethanol; water monomer / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 6 steps 1.1: orthoformic acid triethyl ester / tetrahydrofuran; butan-1-ol / 41 h / 110 - 120 °C 2.1: hydrogenchloride / isopropanol; water monomer / 72 h / 20 °C 3.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 3.2: 21.5 h / 20 - 50 °C 4.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 5.1: N,N-dimethyl-formamide / 22 h / 20 °C 6.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 6 steps 1.1: orthoformic acid triethyl ester / tetrahydrofuran; butan-1-ol / 41 h / 110 - 120 °C 2.1: hydrogenchloride / isopropanol; water monomer / 72 h / 20 °C 3.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 3.2: 21.5 h / 20 - 50 °C 4.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 5.1: ethanol / 5 h / 20 °C 6.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 42
  • 2-acetyl-4,4-dimethoxybutanamide [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 1 h / 20 °C 2.1: orthoformic acid triethyl ester / tetrahydrofuran; butan-1-ol / 41 h / 110 - 120 °C 3.1: hydrogenchloride / isopropanol; water monomer / 72 h / 20 °C 4.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 4.2: 21.5 h / 20 - 50 °C 5.1: ethanol; water monomer / 20 °C 6.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 7 steps 1.1: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 1 h / 20 °C 2.1: orthoformic acid triethyl ester / tetrahydrofuran; butan-1-ol / 41 h / 110 - 120 °C 3.1: hydrogenchloride / isopropanol; water monomer / 72 h / 20 °C 4.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 4.2: 21.5 h / 20 - 50 °C 5.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 6.1: N,N-dimethyl-formamide / 22 h / 20 °C 7.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 7 steps 1.1: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 1 h / 20 °C 2.1: orthoformic acid triethyl ester / tetrahydrofuran; butan-1-ol / 41 h / 110 - 120 °C 3.1: hydrogenchloride / isopropanol; water monomer / 72 h / 20 °C 4.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 4.2: 21.5 h / 20 - 50 °C 5.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 6.1: ethanol / 5 h / 20 °C 7.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 43
  • [ 90213-66-4 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / -5 - 5 °C / Inert atmosphere 1.2: 0.5 h / -5 - 5 °C / Inert atmosphere 1.3: 1 h / -5 - 5 °C / Inert atmosphere 2.1: hydrogen; 5%-palladium/activated carbon / methanol / 3 h / 50 - 55 °C / 760.05 Torr 3.1: bis(trichloromethyl) carbonate / acetonitrile / 0.67 h / 0 - 20 °C 3.2: 20 - 90 °C 4.1: ethanol; water monomer / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 6 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / -5 - 5 °C / Inert atmosphere 1.2: 0.5 h / -5 - 5 °C / Inert atmosphere 1.3: 1 h / -5 - 5 °C / Inert atmosphere 2.1: hydrogen; 5%-palladium/activated carbon / methanol / 3 h / 50 - 55 °C / 760.05 Torr 3.1: bis(trichloromethyl) carbonate / acetonitrile / 0.67 h / 0 - 20 °C 3.2: 20 - 90 °C 4.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 5.1: ethanol / 5 h / 20 °C 6.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 6 steps 1.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / -5 - 5 °C / Inert atmosphere 1.2: 0.5 h / -5 - 5 °C / Inert atmosphere 1.3: 1 h / -5 - 5 °C / Inert atmosphere 2.1: hydrogen; 5%-palladium/activated carbon / methanol / 3 h / 50 - 55 °C / 760.05 Torr 3.1: bis(trichloromethyl) carbonate / acetonitrile / 0.67 h / 0 - 20 °C 3.2: 20 - 90 °C 4.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 5.1: N,N-dimethyl-formamide / 22 h / 20 °C 6.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 44
  • 7-(tert-butyldimethylsilyl)-2-chloro-4-methyl-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: hydrogen; 5%-palladium/activated carbon / methanol / 3 h / 50 - 55 °C / 760.05 Torr 2.1: bis(trichloromethyl) carbonate / acetonitrile / 0.67 h / 0 - 20 °C 2.2: 20 - 90 °C 3.1: ethanol; water monomer / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 5 steps 1.1: hydrogen; 5%-palladium/activated carbon / methanol / 3 h / 50 - 55 °C / 760.05 Torr 2.1: bis(trichloromethyl) carbonate / acetonitrile / 0.67 h / 0 - 20 °C 2.2: 20 - 90 °C 3.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 4.1: ethanol / 5 h / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 5 steps 1.1: hydrogen; 5%-palladium/activated carbon / methanol / 3 h / 50 - 55 °C / 760.05 Torr 2.1: bis(trichloromethyl) carbonate / acetonitrile / 0.67 h / 0 - 20 °C 2.2: 20 - 90 °C 3.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 4.1: N,N-dimethyl-formamide / 22 h / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 45
  • 4-methyl-7H-pyrrolo[2,3-d]pyrimidine hydrochloride [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: bis(trichloromethyl) carbonate / acetonitrile / 0.67 h / 0 - 20 °C 1.2: 20 - 90 °C 2.1: ethanol; water monomer / 20 °C 3.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 4 steps 1.1: bis(trichloromethyl) carbonate / acetonitrile / 0.67 h / 0 - 20 °C 1.2: 20 - 90 °C 2.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 3.1: ethanol / 5 h / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 4 steps 1.1: bis(trichloromethyl) carbonate / acetonitrile / 0.67 h / 0 - 20 °C 1.2: 20 - 90 °C 2.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 3.1: N,N-dimethyl-formamide / 22 h / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 46
  • [ 7400-06-8 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 2.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 3.2: 0 - 15 °C / Large scale 4.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 5.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 6.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 6.2: 21.5 h / 20 - 50 °C 7.1: ethanol; water monomer / 20 °C 8.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 9 steps 1.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 2.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 3.2: 0 - 15 °C / Large scale 4.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 5.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 6.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 6.2: 21.5 h / 20 - 50 °C 7.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 8.1: ethanol / 5 h / 20 °C 9.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 9 steps 1.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 2.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 3.1: sodium hydroxide / water monomer; propan-2-one / 1 h / 20 °C 4.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 5.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 6.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 7.1: trichlorophosphate / 0.5 h / 80 - 90 °C 7.2: pH 7 - 8 7.3: 2 h / 0 - 20 °C 8.1: ethanol / 5 h / 20 °C 9.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 9 steps 1.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 2.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 3.1: sodium hydroxide / water monomer; propan-2-one / 1 h / 20 °C 4.1: Cs2CO3 / N,N-dimethyl-formamide / 50 - 60 °C 5.1: potassium etoxide / ethanol / 12 h / 65 - 75 °C 6.1: sodium hydroxide; water monomer / water monomer; tetrahydrofuran; propan-2-one / 5 h / 20 °C 7.1: trichlorophosphate / 0.5 h / 80 - 90 °C 7.2: pH 7 - 8 7.3: 2 h / 0 - 20 °C 8.1: ethanol / 5 h / 20 °C 9.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 9 steps 1.1: hydrogenchloride / water monomer / 20 - 30 °C / Large scale 2.1: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 0 - 70 °C / Large scale 3.1: sodium hydride / tetrahydrofuran; mineral oil / 0.5 h / 0 - 15 °C / Large scale 3.2: 0 - 15 °C / Large scale 4.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 5.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 6.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 6.2: 21.5 h / 20 - 50 °C 7.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 8.1: N,N-dimethyl-formamide / 22 h / 20 °C 9.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C

Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[4]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[5]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 47
  • C12H18ClN3Si [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 2.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 3.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 3.2: 21.5 h / 20 - 50 °C 4.1: ethanol; water monomer / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 6 steps 1.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 2.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 3.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 3.2: 21.5 h / 20 - 50 °C 4.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 5.1: ethanol / 5 h / 20 °C 6.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 6 steps 1.1: tris(2,4-pentanedionato)iron(III) / tetrahydrofuran; mineral oil / 2 h / -10 - 30 °C / Large scale 2.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 3.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 3.2: 21.5 h / 20 - 50 °C 4.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 5.1: N,N-dimethyl-formamide / 22 h / 20 °C 6.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 48
  • C13H21N3Si [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 2.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 2.2: 21.5 h / 20 - 50 °C 3.1: ethanol; water monomer / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 5 steps 1.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 2.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 2.2: 21.5 h / 20 - 50 °C 3.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 4.1: N,N-dimethyl-formamide / 22 h / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 5 steps 1.1: ammonium hydroxide / methanol; water monomer / 16 h / 15 - 40 °C / Large scale 2.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 2.2: 21.5 h / 20 - 50 °C 3.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 4.1: ethanol / 5 h / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 49
  • C9H15N3O2 [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: hydrogenchloride / isopropanol; water monomer / 72 h / 20 °C 2.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 2.2: 21.5 h / 20 - 50 °C 3.1: ethanol; water monomer / 20 °C 4.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 5 steps 1.1: hydrogenchloride / isopropanol; water monomer / 72 h / 20 °C 2.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 2.2: 21.5 h / 20 - 50 °C 3.1: anhydrous sodium perchlorate / water monomer / 12 h / 20 - 25 °C 4.1: ethanol / 5 h / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Multi-step reaction with 5 steps 1.1: hydrogenchloride / isopropanol; water monomer / 72 h / 20 °C 2.1: oxalyl dichloride / 2.25 h / 20 - 50 °C 2.2: 21.5 h / 20 - 50 °C 3.1: sodium hydroxide / water monomer; N,N-dimethyl-formamide / 30 h / 20 - 40 °C 4.1: N,N-dimethyl-formamide / 22 h / 20 °C 5.1: phosphoric acid / isopropanol; water monomer; dichloromethane / 2 h / 20 - 36 °C
Reference： [1]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[2]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
[3]Current Patent Assignee: INCYTE CORP - US2022/56035, 2022, A1
  • 50
  • tert-butyl (tert-butoxycarbonyl)(6-chloro-5-(2,2-diethoxyethyl)pyrimidin-4-yl)carbamate [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 90 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 4: phosphoric acid / isopropanol; dichloromethane / 20 °C 5: isopropanol
Multi-step reaction with 5 steps 1: potassium carbonate; tetrakis-(triphenylphosphine)-palladium / 1,4-dioxane; lithium hydroxide monohydrate / 1 h / 90 °C / Inert atmosphere 2: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 3: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 4: phosphoric acid / isopropanol; dichloromethane / 20 °C 5: isopropanol
Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 51
  • tert-butyl (tert-butoxycarbonyl)(5-(2,2-diethoxyethyl)-6-(1H-pyrazol-4-yl)pyrimidin-4-yl)carbamate [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 3: phosphoric acid / isopropanol; dichloromethane / 20 °C 4: isopropanol
Multi-step reaction with 4 steps 1: potassium carbonate; N,N-dimethyl acetamide / lithium hydroxide monohydrate; N,N-dimethyl acetamide / 5 h / 0 - 23 °C 2: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 3: phosphoric acid / isopropanol; dichloromethane / 20 °C 4: isopropanol
Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 52
  • tert-butyl (Z)-(tert-butoxycarbonyl)(6-(1-(2-cyano-1-cyclopentylvinyl)-1H-pyrazol-4-yl)-5-(2,2-diethoxyethyl)pyrimidin-4-yl)carbamate [ No CAS ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 2: phosphoric acid / isopropanol; dichloromethane / 20 °C 3: isopropanol
Multi-step reaction with 3 steps 1: bis(cycloocta-1,5-diene)rhodium (I) tetrafluoroborate; hydrogen; Walphos SL-W022-1 / dichloromethane / 22 h / 23 °C / 11251.1 Torr / Sealed tube 2: phosphoric acid / isopropanol; dichloromethane / 20 °C 3: isopropanol
Reference： [1]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
[2]Current Patent Assignee: CONCERT PHARMACEUTICALS INC - WO2020/163653, 2020, A1
  • 53
  • [ 941685-26-3 ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: isopropylmagnesium chloride / dimethyl sulfoxide / -10 - 5 °C / Inert atmosphere 1.2: 0 - 5 °C / Inert atmosphere 2.1: bis(tricyclohexylphosphine)nickel(II) dichloride; potassium acetate / N,N-dimethyl-formamide; water / 65 - 70 °C / Inert atmosphere 3.1: dmap / N,N-dimethyl acetamide / 25 - 30 °C 4.1: D-(+)-camphoric acid / Methyl acetate / 55 - 60 °C 5.1: phosphoric acid / acetone / 55 - 60 °C
Multi-step reaction with 7 steps 1.1: tetrakis(triphenylphosphine) palladium(0) / 1,4-dioxane; water / 90 h / 85 °C / Inert atmosphere 2.1: hydrogenchloride / tetrahydrofuran; water 3.1: potassium carbonate / N,N-dimethyl-formamide / 25 - 30 °C 4.1: isopropyl alcohol; acetonitrile / 25 - 80 °C 5.1: boron trifluoride diethyl etherate / acetonitrile / 25 - 30 °C 6.1: 2,2'-iminobis[ethanol] / 25 - 30 °C 6.2: 25 - 80 °C 7.1: phosphoric acid / acetone / 10 - 50 °C
Reference： [1]Current Patent Assignee: NANJING BAIMAI BIOTECHNOLOGY CO LTD - CN114044777, 2022, A
[2]Current Patent Assignee: NATCO PHARMA LIMITED - WO2023/42224, 2023, A1
  • 54
  • [ CAS Unavailable ]
  • [ 1092939-17-7 ]
YieldReaction ConditionsOperation in experiment
94.6 % With phosphoric acid In acetone at 10 - 50℃; 11 Example-11: PREPARATION OF (R)-3-(4-(7H-PYRROLO[2,3- D]PYRIMIDIN-4-YL)-lH-PYRAZOL-l-YL)-3-CYCLOPENTYLPROPANENITRILE PHOSPHATE (1:1) (RUXOLITINIB PHOSPHATE; 1) (βR)- β-cyclopcntyl-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- 1H-pyrazolc-l -propanenitrile, (2S,3S)-2,3-bis (benzoyloxy)-butanedioic acid (1:1) (90.0g; 17) was reacted with -85% orthophosphoric acid (24.0g) in acetone (2.97L) at 45-50°C for Ih followed by at 25-30°C for 2h and at 10-15°C for 4h, filtered, washed with acetone and dried to afford Ruxolitinib phosphate (51.8g; 94.6% by theory).HPLC purity: >99.5%Chiral purity: >99.5% (by HPLC)
Reference： [1]Current Patent Assignee: NATCO PHARMA LIMITED - WO2023/42224, 2023, A1 Location in patent: Page/Page column 24-25; 5

Tags: 1092939-17-7 synthesis path| 1092939-17-7 SDS| 1092939-17-7 COA| 1092939-17-7 purity| 1092939-17-7 application| 1092939-17-7 NMR| 1092939-17-7 COA| 1092939-17-7 structure

Same Skeleton Products
Related Products
Historical Records