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

HRID 2067979ノート

反応式

HRID 2067979 の反応式
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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-9d1e7d4fed4546f5ba1d80f3fdae4714
出典データセット
uspto-grants-2012_10
特許番号
US08293917B2

反応ノート

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