2-Bromopyridine → (S)-N-{1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1-(pyridin-2-yl)-1H-imidazole-4-carboxamide

HRID 872813Notes

Reaction equation

HRID 872813 reaction equation
N1C2C=CC=CC=2N=N1.Br[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1.[Cl:17][C:18]1[CH:19]=[C:20]([C:26]2[CH:30]=[CH:29][N:28]([CH2:31][C@@H:32]([NH:34][C:35]([C:37]3[N:38]=[CH:39][NH:40][CH:41]=3)=[O:36])[CH3:33])[N:27]=2)[CH:21]=[CH:22][C:23]=1[C:24]#[N:25].CC([O-])(C)C.[K+]>[Cu]I.O.CS(C)=O>[Cl:17][C:18]1[CH:19]=[C:20]([C:26]2[CH:30]=[CH:29][N:28]([CH2:31][C@@H:32]([NH:34][C:35]([C:37]3[N:38]=[CH:39][N:40]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=4)[CH:41]=3)=[O:36])[CH3:33])[N:27]=2)[CH:21]=[CH:22][C:23]=1[C:24]#[N:25]

Participants

8

Reactant 4

HCID 79732-BromopyridineHCID 23665647Potassium tert-butoxideHCID 178418385HCID 178418385, compoundHCID 178461751(S)-N-{1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide

Product 1

HCID 70656133(S)-N-{1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1-(pyridin-2-yl)-1H-imidazole-4-carboxamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A microwave oven reaction tube was charged with CuI (5.5 mg, 0.028 mmol), 1H-benzotriazole (6.7 mg, 0.056 mmol), DMSO (1 ml), 2-bromopyridine (0.054 ml, 89 mg, 0.566 mmol), (S)—N-{1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide (200 mg, 0.564 mmol) and KOt-Bu (89 mg, 0.789 mmol). The reaction mixture was stirred for 30 min at 150° C. in a microwave oven. Then the mixture was cooled to RT, water was added and the product was extracted into ethyl acetate. The combined organic layers were washed with water and dried. After evaporation of the solvent the residue was purified by flash chromatography on silica gel using CH2Cl2-MeOH as a gradient eluent (100:0-99:1). Trituration in diethyl ether provided the desired product. 1H NMR (400 MHz, CDCl3): 1.26 (3H, d), 4.29 (1H, distorted dd), 4.45 (1H, distorted dd), 4.61 (1H, m), 6.62 (1H, d), 7.32 (1H, dd), 7.38 (1H, d), 7.50 (1H, d), 7.66 (1H, d), 7.81 (1H, dd), 7.88 (1H, td), 8.00 (1H, m), 8.18 (2H, m), 8.42 (1H, s), 8.53 (1H, d).

Workup

  1. temperatureThen the mixture was cooled to RT
  2. extractionthe product was extracted into ethyl acetate
  3. washThe combined organic layers were washed with water
  4. customdried
  5. customAfter evaporation of the solvent the residue
  6. customwas purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-50ced04546e64ee085a89dcc70b3ef4a
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

Loading…