Methanesulfonamide → 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-methanesulfonylamino-pyridin-3-yl)-butyl]-amide

HRID 2067979Notes

Reaction equation

HRID 2067979 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:5]=[N:6][CH:7]=1.[CH3:28][S:29]([NH2:32])(=[O:31])=[O:30].C([O-])(=O)C.[Cs+].[Cl-].[NH4+].[Na].C(=O)(O)[O-].[Na+]>CS(C)=O.CCOC(C)=O.[Cu]I>[CH3:28][S:29]([NH:32][C:2]1[CH:3]=[C:4]([CH:8]([NH:12][C:13]([C:15]2[CH:16]=[N:17][N:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:19]=2[CH3:20])=[O:14])[CH2:9][CH2:10][CH3:11])[CH:5]=[N:6][CH:7]=1)(=[O:31])=[O:30]

Participants

9

Reactant 5

HCID 72879MethanesulfonamideHCID 516892Sodium BicarbonateHCID 5152919Cesium acetateHCID 444805971-(4-Chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-bromo-pyridin-3-yl)-butyl]-amideHCID 86657765Sodium ammonium chloride

Product 1

HCID 444805991-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-methanesulfonylamino-pyridin-3-yl)-butyl]-amideYield 37.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-bromo-pyridin-3-yl)-butyl]-amide (100 mg, 0.22 mmol), methanesulfonamide (85 mg, 0.89 mmol), copper(I) iodide (210 mg, 1.1 mmol) and cesium acetate (260 mg, 1.3 mmol) in DMSO (3 mL) is heated at 130° C. for 18 hours. After cooling to room temperature, saturated aqueous sodium ammonium chloride (2 mL) and saturated aqueous sodium bicarbonate (1 mL) are added and the resultant mixture is stirred for 30 min. The crude mixture is diluted with EtOAc (50 mL) and washed with saturated aqueous sodium ammonium chloride (25 mL), saturated aqueous sodium bicarbonate (25 mL) and brine (25 mL). The combined organic layers are dried over magnesium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (eluted with 0 to 6% MeOH/CH2Cl2) affords 1-(4-chloro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acid [1-(5-methanesulfonylamino-pyridin-3-yl)-butyl]-amide as an off-white solid (38 mg, 36%).

Workup

  1. washwashed with saturated aqueous sodium ammonium chloride (25 mL), saturated aqueous sodium bicarbonate (25 mL) and brine (25 mL)
  2. dry with materialThe combined organic layers are dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by flash chromatography on silica gel (eluted with 0 to 6% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-9d1e7d4fed4546f5ba1d80f3fdae4714
Source dataset
uspto-grants-2012_10
Patent number
US08293917B2

Reaction notes

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