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Chemical Structure| 480424-93-9 Chemical Structure| 480424-93-9

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Chemical Structure| 480424-93-9

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Product Details of [ 480424-93-9 ]

CAS No. :480424-93-9
Formula : C14H20BNO3
M.W : 261.12
SMILES Code : CC(NC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=C1)=O
MDL No. :MFCD03789261
InChI Key :CZFSGYCLOCCASM-UHFFFAOYSA-N
Pubchem ID :2773989

Safety of [ 480424-93-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 480424-93-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 19
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 77.23
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

47.56 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.08
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.75
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.13
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.46
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.28

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.81
Solubility 0.409 mg/ml ; 0.00157 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.71
Solubility 0.511 mg/ml ; 0.00196 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-4.39
Solubility 0.0107 mg/ml ; 0.000041 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

Yes
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.42 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<0.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.79

Application In Synthesis of [ 480424-93-9 ]

* 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 [ 480424-93-9 ]

[ 480424-93-9 ] Synthesis Path-Downstream   1~32

  • 1
  • [ 862170-53-4 ]
  • [ 480424-93-9 ]
  • [ 1001084-23-6 ]
YieldReaction ConditionsOperation in experiment
49% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 155℃; for 0.5h;Microwave; A mixture of (2-6-dichloro-3-pyridinyl)(4-methyloxyphenyl)methanone (300 mg, 1.06 mmol), 3 -(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)acetanilide, potassium carbonate (200 mg), tetrakis(triphenylphosphine)palladium (80 mg) in THF (4 mL) was flashed with argon and then subjected to microwave at 155 0C for 30 min. THF was removed and absorbed onto silica, then purified by flash column chromatography over silica gel, using polarity gradient 5-50% EtOAc in hexane to yield acetanilide derivative 3 (200 mg 49 %) as a yellow oil; 1H NMR (600 MHz DMSO-d6) 10.17 (s, IH), 8.32 (s, IH), 8.08 (s, 2H), 7.81 (m, 4H), 7.47 (t, IH, / = 7.8 Hz), 7.10 (d, 2H, / = 9.0 Hz), 3.87 (s, 3H), 2.08 (s, 3H); 13C NMR delta 191.3, 168.5, 164.2, 157.4, 145.9, 140.1, 139.5, 136.8, 133.1, 132.3, 129.5, 128.4, 121.5, 120.8, 119.2, 117.3, 114.5, 55.7, 24.0; MS (C2iH17ClN2O3) calcd. 380.093 found 381.3.
  • 2
  • [ 108-24-7 ]
  • [ 210907-84-9 ]
  • [ 480424-93-9 ]
YieldReaction ConditionsOperation in experiment
78% at 80℃; for 12h; Example 4 N-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetamide through halogen-metal exchange using n-butyllithium at benzhydryliden-(4-bromo-phenyl)-amine The synthetic of 3-aminophenylboronic acid pinacol ester is carried out as described in example 1. After completion of pinacolisation and phase separation the mixture is, however, not concentrated, rather the remaining organic phase is azeotropically dried. The residue, after adding 7.3 g (71.5 mmole) of acetic acid anhydride is stirred at 80 C. for 12 h. Thereafter the bulk of the solvent is removed by distillation and the mixture is cooled to -5 C. Thereby the product crystallizes in the form of colorless crystals and can be isolated by filtration. Thus, 9.37 g (35.9 mmole, 78%) of N-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetamide are obtained. Yield over all steps: 60%.
  • 3
  • [ 480424-93-9 ]
  • [ 74-88-4 ]
  • [ 1231257-90-1 ]
YieldReaction ConditionsOperation in experiment
75% Lambda/-Methyl-N-(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)acetamide [00294] N-(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)acetamide (1.0 g, 3.83 mmol) was dissolved in anhydrous THF (32 mL). Sodium hydride (306 mg, 7.66 mmol - 60% in mineral oil) was added and the resulting cloudy white mixture stirred at 2O0C for 30 minutes under an N2 atmosphere. Methyl iodide (716 muL, 11.49 mmol) was added dropwise and the mixture stirred at 2O0C for 16 hours. The reaction mixture was partitioned between EtOAc (100 mL). The aqueous layer was acidified with IM HClaq and re-extracted with EtOAc (100 mL). The organic extracts were combined, dried over MgSO4, and concentrated in vacuo to give a pale yellow oil (1.34 g). Column chromatography (0:1 - 1 :3 EtOAc: petroleum ether gradient) gave the title compound as a clear oil (791 mg, 75%). LCMS RT = 1.95 min MH+ 276.4. 1H NMR (d6-DMSO): 7.63 (IH, s), 7.51 (IH, s), 7.46 (2H, m), 3.15 (3H, s), 1.30 (12H, s), 1.07 (3H, s).
60% N-Methyl-N-(3-(4'.4'.5'.5'-tetramethyl-r.3'.2'-dioxaborolan-2'-vpphenvpacetamide [00257] A solution of N-(3-(4>,4>,5',5'-tetramethyl-r,3>,2>-dioxaborolan-2>- yl)phenyl)acetamide (500 mg, 1.915 mmol) in anhydrous THF (10.0 mL) was transferred via a canula to a mixture of sodium hydride (60% in mineral oil; 153 mg, 3.830 mmol) and anhydrous THF (10.0 mL) under a nitrogen atmosphere and the resulting mixture was stirred at room temperature for 30 minutes. Methyl iodide (0.36 mL, 5.745 mmol) was then added and stirring continued for 16 hours. The reaction mixture was then quenched with ammonium chloride (sat. aq.), followed by extraction into EtOAc. The organic layer was dried (MgSO4), concentrated in vacuo and purified by flash column chromatography (3:1 EtOAc:40-60 petrol) to give the title compound (317 mg, 60%). 1U NMR (d6-DMSO): 7.68- 7.57 (IH, br s), 7.53-7.40 (3H, br m), 3.14 (3H, s), 1.73 (3H, s), 1.30 (12H, s).
  • 4
  • [ 480424-93-9 ]
  • [ 1227089-75-9 ]
  • [ 1227089-91-9 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; acetonitrile; at 130℃; for 0.333333h;Microwave irradiation; Example 22 N-(3-(6-(lH-indazol-4-yl)-l-methyl-lH-pyrazolo[3,4- b]pyridin-4-yl)phenyl)acetamide 112[00235] 4-Chloro-6-(lH-indazol-4-yl)-l -methyl- lH-pyrazolo [3, 4-b]pyridine 7 (80 mg,0.28 mmol) and 3'-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)acetanilide (1.4 equiv.) were suspended in 2 ml acetonitrile. Sodium carbonate (3 equiv., 92 mg) and bis(triphenylphosphine)palladium(II) chloride (0.05 equiv.) were added as a solution in water(0.5 ml). The reaction mixture was heated in microwave at 130 0C for 20 min. Water was added to the mixture, and the precipitated product was filtered and purified by column chromatography to yield 112. NMR (CDC13): 2.27 (3H, s), 4.33 (3H, s), 7.34 (IH, br), 7.52-7.68 (5H, m), 7.84 (IH, d), 7.85 (IH, s), 8.10 (IH, s), 8.26 (IH, s), 8.96 (IH, s). MS: MH+383.12 (100%)
  • 5
  • [ 480424-93-9 ]
  • [ 1041114-10-6 ]
  • [ 1064680-90-5 ]
  • 6
  • [ 480424-93-9 ]
  • [ 75-03-6 ]
  • [ 1224288-99-6 ]
  • 7
  • [ 76-09-5 ]
  • [ 78887-39-5 ]
  • [ 480424-93-9 ]
  • 8
  • [ 480424-93-9 ]
  • [ 39478-78-9 ]
  • [ 1190222-36-6 ]
YieldReaction ConditionsOperation in experiment
74% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; for 7h;Reflux; (i) N-(3'-amino-4'-methylbiphenyl-3-yl)acetamido; 0.67 g (3.61 mmol) of 5-bromo-2-methylaniline and 1.14 g (4.37 mmol) of <strong>[480424-93-9]3-acetamidophenyl boronic acid pinacol ester</strong> were dissolved in 15 mL of DME. Subsequently, 5 mL of a 2M aqueous sodium carbonate solution, and then 417 mg (0.36 mmol) of tetrakis(triphenyl phosphine)palladium (0) were added to the mixture, and the mixture was heated under reflux for 7 hours. After completion of the reaction, ethyl acetate and water were added to the reaction mixture. The organic layer was separated, washed with a saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. Filtration was conducted, and the filtrate was condensed. The resulting crude product was separated and purified using silica gel column chromatography to give N-(3'-amino-4'-methylbiphenyl-3-yl)acetamido (yield: 74%). 1H-NMR (CDCl3) delta: 2.19 (3H, s), 2.20 (3H, s), 3.68 (2H, br), 6.88-6.94 (2H, m), 7.10 (1H, d, J = 7.4 Hz), 7.30-7.69 (5H, m).
  • 10
  • [ 621-38-5 ]
  • [ 73183-34-3 ]
  • [ 480424-93-9 ]
YieldReaction ConditionsOperation in experiment
51% With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 85℃;Inert atmosphere; Step 34b: N-(3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)acetamide (Compound 0602-107)To a solution of compound 0601-107 (2.5 g, 11.6 mmol) and bis(pinacolato)diboron (4.4 g, 17.5 mmol) in dioxane (100 mL) was added potassium acetate (3.4 g, 35 mmol) and PdCl2(dppf)2 (0.95 g, 1.1 mmol). The mixture was degassed with nitrogen and heated at 85 C for overnight. The reaction mixture was concentrated under reduced pressure to afford the crude product, which purified by column chromatography (ethyl acetate in petroleum ether, 15% v/v) to give the compound 0602-107 (1.55 g, 51%) as a pink solid. LCMS: 262 [M+l]+. 1H NMR (400 MHz, DMSO-d6) delta 1.29 (s, 12H), 2.03 (s, 3H), 7.30 (s, 1H), 7.31 (d, J= 2.0 Hz 1H), 7.73 (d, J= 2.0 Hz, 1H), 7.89 (d, J= 1.6 Hz, 1H), 9.93 (s, 1H).
51% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 85℃;Inert atmosphere; Step 34b: N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide (Compound 0602-107)[0334]To a solution of compound 0601-107 (2.5 g, 11.6 mmol) and bis(pinacolato)diboron (4.4 g, 17.5 mmol) in dioxane (100 mL) was added potassium acetate (3.4 g, 35 mmol) and PdCl2(dppf)2 (0.95 g, 1.1 mmol). The mixture was degassed with nitrogen and heated at 85 C. for overnight. The reaction mixture was concentrated under reduced pressure to afford the crude product, which purified by column chromatography (ethyl acetate in petroleum ether, 15% v/v) to give the compound 0602-107 (1.55 g, 51%) as a pink solid. LCMS: 262 [M+1]+. 1H NMR (400 MHz, DMSO-d6) delta 1.29 (s, 12H), 2.03 (s, 3H), 7.30 (s, 1H), 7.31 (d, J=2.0 Hz 1H), 7.73 (d, J=2.0 Hz, 1H), 7.89 (d, J=1.6 Hz, 1H), 9.93 (s, 1H).
51% With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium acetate; In 1,4-dioxane; at 85℃;Inert atmosphere; Compound in dioxane (100mL) 0601-107 (2.5g, 11.6mmol) and a solution of bis (pinacolato) diboron (4.4 g, 17.5 mmol), potassium acetate (3.4 g, 35 mmol) and and PdCl2 (dppf) 2 ( 0.95g, 1.1mmol) was added. The mixture was degassed with nitrogen and heated overnight at 85 C.. The reaction mixture was concentrated under reduced pressure to give the crude product, which was purified by column chromatography (petroleum ether in ethyl acetate, 15% v / v) to give the compound 0602-107 as a pink solid obtained (1.55 g, 51%).
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; for 2h;Reflux; Inert atmosphere; General procedure: A mixture of substituted 3-(or 4-) bromobenzamides or 3-bromobenzoate or N-(3-(or 4-)bromophenyl)acetamide 3, (0.5 mmol), bis(pinacolato)diboron (0.14 g, 0.55 mmol), potassium acetate (0.15 g, 1.5 mmol), PdCl2(dppf) (0.03 g, 0.04 mmol) and 1,4-dioxane (10 mL) was refluxed for 2 h under nitrogen atmosphere. The solvent was evaporated under reduced pressure to afford a dark brown residue. To the residue was added intermediate 2 (0.4 mmol), sodium carbonate (0.16 g, 1.5 mmol), PdCl2(dppf) (0.03 g, 0.04 mmol), 1,2-dimethoxyethane (8 mL) and water (2 mL) and the mixture was refluxed for 2 h under nitrogen atmosphere. The mixture was evaporated under reduced pressure and purified by silica gel column chromatography using chloroform/methanol = 30: 1 as the eluent to afford the compounds T1-T6, T9-T10, T12 and T14-T21 as an off-white or a white solid.
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 80℃;Combinatorial reaction / High throughput screening (HTS); Triethylamine (1.2 equiv) and acetic anhydride (1.5 equiv) inCH2Cl2 were added to a solution of 3-bromoaniline (1 equiv). Thereaction mixture was stirred at rt. Upon completion, the mixturewas diluted with water and extracted with CH2Cl2. The organicphases were combined, washed with saline, dried over anhydrousNa2SO4 and evaporated to afford crude product 13. Pd(dppf)Cl2(0.05 equiv) was added to a solution of compound 13 (1 equiv),bis(pinacolato)diboron (1.2 equiv), and AcOK (3 equiv) in dioxane.The mixture was degassed with nitrogen and heated at 80 Covernight. The mixture was diluted with ethyl acetate, and theorganic layerwaswashed with saline, dried over anhydrous Na2SO4and filtered. The filtrate was concentrated and purified usingchromatography to provide the coupling intermediate 14. MS (ESI)m/z(%): 262.1 [MH].

  • 11
  • [ 588-07-8 ]
  • [ 73183-34-3 ]
  • [ 480424-93-9 ]
YieldReaction ConditionsOperation in experiment
93% With (2,2,2-trifluoroethoxy)trimethylsilane; cesium fluoride; dichlorobis(trimethylphosphine)nickel; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere; Sealed tube; Under an argon atmosphere,To the reaction vessel, 1.4 mg (0.005 mmol) of dichlorobis (trimethylphosphine) nickel,N- (3- chlorophenyl) acetamide 85.1 mg (0.5 mmol),152 mg (1.0 mmol) of cesium fluoride,140 mg (0.55 mmol) of 4,4,5,5,4 ', 4', 5 ', 5'-octamethyl-2,2'-bi (1,3,2-dioxaborolanyl)180 mg (1.05 mmol) of trimethyl (2,2,2-trifluoroethoxy) silane and 0.5 mL of 1,4-dioxane were added and sealed,And the mixture was stirred at 100 C. for 12 hours.After the reaction vessel was cooled to room temperature, 1 mL of a saturated aqueous solution of ammonium chloride was added, and the mixture was extracted three times with 8 mL of ethyl acetate, and the obtained organic phases were combined. The solvent was distilled off under reduced pressure, and the residue was purified using silica gel column chromatography (hexane: chloroform: ethyl acetate = 4: 1: 0 to 4: 1: 1)N- [3- (4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] acetamide 122 mg (white solid, 93% yield)
  • 12
  • [ 480424-93-9 ]
  • [ 1377503-74-6 ]
  • N-(3-(3-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)acetamide [ No CAS ]
  • 13
  • [ 480424-93-9 ]
  • [ 1330595-43-1 ]
  • C25H32N6O3 [ No CAS ]
  • 14
  • [ 480424-93-9 ]
  • [ 1610520-84-7 ]
  • [ 1610518-31-4 ]
YieldReaction ConditionsOperation in experiment
30% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,2-dimethoxyethane; water; at 120℃; for 0.333333h;Microwave irradiation; A mixture of 7-bromo-5-methyl-2-((4-(methylsulphonyl)piperazin-1 -yl)methyl)thieno[3,2-c]pyridin- 4(5H)-one (for a preparation see Intermediate 69, 210 mg, 0.5 mmol), A/-(3-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)phenyl)acetamide (261 mg, 1.0 mmol), potassium carbonate (346 mg, 2.5 mmol) and 5/s(triphenylphosphine)palladium(ll) chloride (35 mg, 10 mol%) in 1 ,2-dimethoxyethane (3 mL) and water (0.5 mL) was heated in a microwave at 120 C for 20 minutes. The cooled reaction mixture was diluted with ethyl acetate (25 mL). The solution was dried over sodium sulphate and evaporated. The residue was purified by chromatography on silica gel eluting with 0-5% methanol in dichloromethane (twice) and the product triturated with diethyl ether to give A/-(3-(5-methyl-2-((4- (methylsulphonyl)piperazin-1 -yl)methyl)-4-oxo-4,5-dihydrothieno[3,2-c]pyridin-7-yl)phenyl)acetamide (71 mg, 0.150 mmol, 30% yield) as a yellow solid. LCMS (2 min, Formic Acid): Rt = 0.57 min, MH+ = 475.
  • 15
  • [ 480424-93-9 ]
  • [ 1261082-88-5 ]
  • N-(3-(3-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)phenyl)acetamide [ No CAS ]
  • 16
  • [ 39217-02-2 ]
  • [ 480424-93-9 ]
  • N-(3-(6,7-dimethoxy-4-morpholinoquinazolin-2-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,2-dimethoxyethane; water; for 2h;Reflux; Inert atmosphere; General procedure: A mixture of substituted 3-(or 4-) bromobenzamides or 3-bromobenzoate or N-(3-(or 4-)bromophenyl)acetamide 3, (0.5 mmol), bis(pinacolato)diboron (0.14 g, 0.55 mmol), potassium acetate (0.15 g, 1.5 mmol), PdCl2(dppf) (0.03 g, 0.04 mmol) and 1,4-dioxane (10 mL) was refluxed for 2 h under nitrogen atmosphere. The solvent was evaporated under reduced pressure to afford a dark brown residue. To the residue was added intermediate 2 (0.4 mmol), sodium carbonate (0.16 g, 1.5 mmol), PdCl2(dppf) (0.03 g, 0.04 mmol), 1,2-dimethoxyethane (8 mL) and water (2 mL) and the mixture was refluxed for 2 h under nitrogen atmosphere. The mixture was evaporated under reduced pressure and purified by silica gel column chromatography using chloroform/methanol = 30: 1 as the eluent to afford the compounds T1-T6, T9-T10, T12 and T14-T21 as an off-white or a white solid.
  • 17
  • [ 480424-93-9 ]
  • 1-(2,3-dihydro-1H-inden-2-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
  • N-{3-[4-amino-1-(2,3-dihydro-1H-inden-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]phenyl}acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 90℃; for 3h; To a solution of i-indan-2-yl-3-iodo-pyrazolo[3,4-d]pyrimidin-4-amine (300 mg, 0.79 mmol) and N- [3-(4,4,5 ,5-tetramethyl- i ,3 ,2-dioxaborolan-2-yl)phenyl] acetamide (4 i 5 mg, i .59 mmol) in N,N-dimethylformamide (3 mL) was added a solution of sodium carbonate (i68 mg, i.59 mmol) in water (3 mL) followed by the addition of tetrakis(triphenyl phosphine)palladium(0) (9i mg, 0.079 mmol). The reaction mixture was heated in a reagent bottle at 90 C for 3 h. The progress of reaction was monitored by TLC. After completion of reaction, water (iO mL) was added to the reaction mixture and the product was extracted using EtOAc (2x50 mL). The combined organic layer was again washed with water (3x30 mL) and brine (30 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to obtain a crude product which was purified by reverse phase preparative HPLC giving N- [3- (4-amino-i -indan-2-yl-pyrazolo [3 ,4-d]pyrimidin-3- yl)phenyl]acetamide as the formate salt (i4.44 mg). ?HNMR (400 MHz, DMSO-d6) oe (ppm):iO.i7 (s, iH), 8.27 (s, iH), 7.89 (s, iH), 7.59 (d, I = 8.3 Hz, iH), 7.44 (t, 1=7.9 Hz, iH), 7.35 - 7.24 (m, 3H), 7.24 - 7.09 (m, 2H), 6.29 (s, iH), 5.74 (m, iH), 3.49 (d, I = 8.0 Hz, 4H),2.06 (s, 3H).
  • 18
  • [ 480424-93-9 ]
  • 4-(5-bromothiophene-2-carboxamido)-N-(5-(3-(dimethylamino) propylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide [ No CAS ]
  • 4-(5-(3-acetamidophenyl)thiophene-2-carboxamido)-N-(5-(3-(dimethylamino) propylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 0.166667h;Inert atmosphere; Microwave irradiation; General procedure: Pd(PPh3)4 (0.2 equiv) was added under a nitrogen atmosphere to a solution of bromopolyamides 6(1-5) (0.2 mmol), the appropriate boronic acid/ester 4(1-7) (1.2 equiv) and K2CO3 (3 equiv) in a mixture of ethanol, toluene and water (1:1:0.2) (2.2 mL) in a10 mL microwave vial containing a magnetic stirrer. The reaction mixture was sealed in an inert N2 environment and heated with microwave radiation in an EMRYS Optimizer Microwave Station (Personal Chemistry) at 100 C for the required amount oftime (see Supporting information). After LC-MS analysis revealed the absence of starting material, the reaction mixture was passed through an Isolute SCX-2 cartridge and washed with CH2Cl2 (3 10 mL), DMF (3 10 mL) and MeOH (2 10 mL). Subsequently, a solution of NH3 in MeOH (60 mL, 2 M) was employed to release the product from the cartridge. After removing MeOH under reduced pressure, the crude mixture was purified using a preparative HPLC coupled to a mass directed fraction collector. Pure fractions were combined and lyophilised to yield the solid product.
  • 19
  • [ 480424-93-9 ]
  • 4-(5-bromofuran-2-carboxamido)-N-(5-(3-(dimethylamino) propyl carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide [ No CAS ]
  • 4-(5-(3-acetamidophenyl)furan-2-carboxamido)-N-(5-(3-(dimethylamino)propylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 0.133333h;Inert atmosphere; Microwave irradiation; General procedure: Pd(PPh3)4 (0.2 equiv) was added under a nitrogen atmosphere to a solution of bromopolyamides 6(1-5) (0.2 mmol), the appropriate boronic acid/ester 4(1-7) (1.2 equiv) and K2CO3 (3 equiv) in a mixture of ethanol, toluene and water (1:1:0.2) (2.2 mL) in a10 mL microwave vial containing a magnetic stirrer. The reaction mixture was sealed in an inert N2 environment and heated with microwave radiation in an EMRYS Optimizer Microwave Station (Personal Chemistry) at 100 C for the required amount oftime (see Supporting information). After LC-MS analysis revealed the absence of starting material, the reaction mixture was passed through an Isolute SCX-2 cartridge and washed with CH2Cl2 (3 10 mL), DMF (3 10 mL) and MeOH (2 10 mL). Subsequently, a solution of NH3 in MeOH (60 mL, 2 M) was employed to release the product from the cartridge. After removing MeOH under reduced pressure, the crude mixture was purified using a preparative HPLC coupled to a mass directed fraction collector. Pure fractions were combined and lyophilised to yield the solid product.
  • 20
  • [ 480424-93-9 ]
  • 4-bromo-N-(5-(5-(3-(dimethylamino)propylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide [ No CAS ]
  • 4-(3-acetamidophenyl)-N-(5-(5-(3-(dimethylamino)propylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 0.166667h;Inert atmosphere; Microwave irradiation; General procedure: Pd(PPh3)4 (0.2 equiv) was added under a nitrogen atmosphere to a solution of bromopolyamides 6(1-5) (0.2 mmol), the appropriate boronic acid/ester 4(1-7) (1.2 equiv) and K2CO3 (3 equiv) in a mixture of ethanol, toluene and water (1:1:0.2) (2.2 mL) in a10 mL microwave vial containing a magnetic stirrer. The reaction mixture was sealed in an inert N2 environment and heated with microwave radiation in an EMRYS Optimizer Microwave Station (Personal Chemistry) at 100 C for the required amount oftime (see Supporting information). After LC-MS analysis revealed the absence of starting material, the reaction mixture was passed through an Isolute SCX-2 cartridge and washed with CH2Cl2 (3 10 mL), DMF (3 10 mL) and MeOH (2 10 mL). Subsequently, a solution of NH3 in MeOH (60 mL, 2 M) was employed to release the product from the cartridge. After removing MeOH under reduced pressure, the crude mixture was purified using a preparative HPLC coupled to a mass directed fraction collector. Pure fractions were combined and lyophilised to yield the solid product.
  • 21
  • [ 480424-93-9 ]
  • 2-bromo-N-(5-(5-(3-(dimethylamino)propylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)-4-methylthiazole-5-carboxamide [ No CAS ]
  • 2-(3-acetamidophenyl)-N-(5-(5-(3-(dimethylamino)propylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)-4-methylthiazole-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 0.166667h;Inert atmosphere; Microwave irradiation; General procedure: Pd(PPh3)4 (0.2 equiv) was added under a nitrogen atmosphere to a solution of bromopolyamides 6(1-5) (0.2 mmol), the appropriate boronic acid/ester 4(1-7) (1.2 equiv) and K2CO3 (3 equiv) in a mixture of ethanol, toluene and water (1:1:0.2) (2.2 mL) in a10 mL microwave vial containing a magnetic stirrer. The reaction mixture was sealed in an inert N2 environment and heated with microwave radiation in an EMRYS Optimizer Microwave Station (Personal Chemistry) at 100 C for the required amount oftime (see Supporting information). After LC-MS analysis revealed the absence of starting material, the reaction mixture was passed through an Isolute SCX-2 cartridge and washed with CH2Cl2 (3 10 mL), DMF (3 10 mL) and MeOH (2 10 mL). Subsequently, a solution of NH3 in MeOH (60 mL, 2 M) was employed to release the product from the cartridge. After removing MeOH under reduced pressure, the crude mixture was purified using a preparative HPLC coupled to a mass directed fraction collector. Pure fractions were combined and lyophilised to yield the solid product.
  • 22
  • [ 480424-93-9 ]
  • 7-bromo-5-(1-cyclohexyl-1H-pyrazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine [ No CAS ]
  • N-(3-(4-amino-5-(1-cyclohexyl-1H-pyrazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl)phenyl)acetamide [ No CAS ]
  • 24
  • [ 103-84-4 ]
  • [ 73183-34-3 ]
  • [ 480424-93-9 ]
  • N-(3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide [ No CAS ]
  • [ 214360-60-8 ]
  • 25
  • [ 103-84-4 ]
  • [ 73183-34-3 ]
  • N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide [ No CAS ]
  • [ 480424-93-9 ]
  • N-(3,5-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide [ No CAS ]
  • [ 214360-60-8 ]
  • 26
  • [ 480424-93-9 ]
  • C12H12BrN3O [ No CAS ]
  • 5-(3-acetamidophenyl)-2-amino-4-ethyl-[3,4'-bipyridine]-1'-oxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium carbonate; In 1,4-dioxane; water; at 80℃; for 16h;Inert atmosphere; General procedure: into a 250-ml three-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen were placed 4-(2-amino-5-bromo-4-ethylpyridin-3-yl)phenol (1.0 g, 3.41 mmol), 6-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (880 mg, 3.41 mmol,), potassium carbonate (3.3 g, 23.88 mmol), water (30 ml), 1,4-dioxane (25 ml), and Pd(dppf)Cl2 (200 mg, 0.3 mmol). The resulting solution was stirred at 80 C for 16 h, and diluted with 500 ml H2O and 500 ml ethylacetate.The organic layer was washed twice with brine (2 × 250 ml) and concentrated under vacuum. The residue was purified on a silica gel column eluting with DCM/CH3OH (20:1-10:1) to afford the title compound.
  • 27
  • [ 480424-93-9 ]
  • 6-((4-chloro-6-morpholino-1,3,5-triazin-2-yl)amino)hexan-1-ol [ No CAS ]
  • N-(3-(4-((6-hydroxyhexyl)amino)-6-morpholino-1,3,5-triazin-2-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; triphenylphosphine; In N,N-dimethyl acetamide; at 100℃; for 0.833333h;Inert atmosphere; Microwave irradiation; Firstly, 6-((4-chloro-6-morpholino-1,3,5-triazin-2-yl)amino)hexan-1-ol (10a, Scheme 3; 0.063 g,0.2 mmol) and <strong>[480424-93-9]N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide</strong> (0.166 g, 0.4 mmol)were combined with DME (4 mL) and 2 M Na2CO3 (1 mL, 2.0 mmol). The reaction mixture wasdegassed with nitrogen, and PPh3 (0.021 g, 0.08 mmol) and Pd2(dba)3 (0.037 g, 0.04 mmol) werequickly added. The reaction mixture was placed in the CEM Discover under 300 W and 100 Cconditions, and was set to hold for 30 minutes. After the completion time of 50 minutes, the reactionmixture was greenish black. The reaction was allowed to cool in an ice bath, was quenched withwater (10 mL), and was extracted with ethyl acetate (3 10 mL). The organic layer was dried usingNaSO4, and was filtered and condensed by rotary evaporation. The product was purified with columnchromatography on silica gel with a 1:1 ethyl acetate and heptane solvent mobile phase to giveN-(3-(4-((6-hydroxyhexyl)amino)-6-morpholino-1,3,5-triazin-2-yl)phenyl)acetamide (11c, Scheme 3;0.057g, 0.14 mmol, 69%): Rf 0.04 (1:1 ethyl acetate in heptane) as a light-brown solid. 1H-NMR(300 MHz, DMSO-d6) delta 10.04 (s, 1H), 8.42 (s, 1H), 8.04-7.74 (m, 2H), 7.50-7.29 (m, 2H), 4.32 (t, J = 5.1 Hz,1H), 3.66 (d, J = 4.9 Hz, 6H), 3.44-3.22 (m, 6H), 2.06 (s, J = 1.6 Hz, 3H), 1.36-1.27 (m, 8H). 13C-NMR(75 MHz, DMSO-d6) delta 169.00, 168.20, 165.59, 164.43, 139.12, 137.43, 128.28, 122.44, 121.72, 118.58,65.88, 60.58, 43.07, 32.43, 29.24, 28.75, 26.22, 25.14, 23.87. HRMS [M + H]+ calculated for C21H30N6O3:415.2379 Found: 415.2450.
  • 28
  • [ 480424-93-9 ]
  • tert-butyl 4-(4-((7-bromobenzo[d]oxazol-2-yl)amino)phenyl)piperazine-1-carboxylate [ No CAS ]
  • tert-butyl4-(4-((7-(3-acetamidophenyl)benzo[d]oxazol-2-yl)amino)phenyl)piperazine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; sodium carbonate; In Dimethyl ether; water; at 100℃; for 8h;Inert atmosphere; General procedure: To a suspension of 4a (0.1 g, 0.21 mmol) and (1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)boronic acid (0.057 g,0.25 mmol) in dimethyl ether (DME)/H2O (4 mL) were added Na2CO3(0.06 g, 0.63 mmol) and Pd(dppf)2Cl2 (0.034g, 0.04 mmol) under argon atmosphere, which was allowed to react at 100 C for 8 h. After cooling, water (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (15 mL×3). The organic layer was driedover MgSO4. The solvent was removed in vacuo and the residue waspurified by silica gel chromatography (Developing solvent: PE/EA=3/1) to give 5a (0.09 g, yield 75.2%).
  • 29
  • [ 480424-93-9 ]
  • [ 1334419-88-3 ]
  • C19H18N4O2 [ No CAS ]
  • 30
  • [ 480424-93-9 ]
  • 6-bromo-N-(4-((1S,4S)-5-isopropyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)imidazo[1,2-a]pyrazin-8-amine [ No CAS ]
  • N-(3-(8-((4-((1S,4S)-5-isopropyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)amino)imidazo[1,2-a]pyrazin-6-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere; General procedure: Heteroarylboronicester (1.2 mmol), 7a, 11a-11g (1 mmol), PdCl2(dppf) (82 mg,0.1 mmol), sodium carbonate(1.5 mL, 1.5 mmol, 1 M aqueous solution),dissolved in 1,4-dioxane (15 mL) and the mixture was heated at 100 Cunder argon atmosphere overnight. After that, the flask was cooled toroom temperature and the reaction solution was filtered with celitewhile washing with dichloromethane. The solvent was then evaporatedand the residue was purified by flash column chromatography to givethe key intermediates 12a-12b and the final products 8a, 12c-12k.
  • 31
  • [ 480424-93-9 ]
  • 6-bromo-N-(4-((1R,4R)-5-isopropyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)imidazo[1,2-a]pyrazin-8-amine [ No CAS ]
  • N-(3-(8-((4-((1R,4R)-5-isopropyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)amino)imidazo[1,2-a]pyrazin-6-yl)phenyl)acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
26% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere; General procedure: Heteroarylboronicester (1.2 mmol), 7a, 11a-11g (1 mmol), PdCl2(dppf) (82 mg,0.1 mmol), sodium carbonate(1.5 mL, 1.5 mmol, 1 M aqueous solution),dissolved in 1,4-dioxane (15 mL) and the mixture was heated at 100 Cunder argon atmosphere overnight. After that, the flask was cooled toroom temperature and the reaction solution was filtered with celitewhile washing with dichloromethane. The solvent was then evaporatedand the residue was purified by flash column chromatography to givethe key intermediates 12a-12b and the final products 8a, 12c-12k.
  • 32
  • [ 193805-02-6 ]
  • [ 73183-34-3 ]
  • [ 480424-93-9 ]
 

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