Water → 1-{1-[1-(2,6-Difluoro-benzoyl)-piperidin-4-yloxy]-isoquinolin-4-yl}-3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea

HRID 729627ノート

反応式

HRID 729627 の反応式
Cl.[F:2][CH2:3][C:4]([C:8]1[CH:9]=[C:10]([NH:20][C:21]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([O:34][CH:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)=[N:26][CH:25]=2)=[O:22])[N:11]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[N:12]=1)([CH2:6][F:7])[CH3:5].[F:41][C:42]1[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[C:43]=1[C:44](Cl)=[O:45].C(N(CC)CC)C.O>ClCCl>[F:41][C:42]1[CH:50]=[CH:49][CH:48]=[C:47]([F:51])[C:43]=1[C:44]([N:38]1[CH2:39][CH2:40][CH:35]([O:34][C:27]2[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:24]([NH:23][C:21]([NH:20][C:10]3[N:11]([C:13]4[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=4)[N:12]=[C:8]([C:4]([CH2:6][F:7])([CH3:5])[CH2:3][F:2])[CH:9]=3)=[O:22])=[CH:25][N:26]=2)[CH2:36][CH2:37]1)=[O:45]

参加物

6

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 690537531-[5-(2-Fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-[1-(piperidin-4-yloxy)-isoquinolin-4-yl]-urea hydrochloride

生成物 1

HCID 690550751-{1-[1-(2,6-Difluoro-benzoyl)-piperidin-4-yloxy]-isoquinolin-4-yl}-3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-urea

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

Stir 1-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-[1-(piperidin-4-yloxy)-isoquinolin-4-yl]-urea hydrochloride (Preparation 37, 0.6 mmol, 0.3 g), 2,6-difluorobenzoyl chloride (0.6 mmol, 0.07 mL) and triethylamine (1.7 mmol, 0.2 mL) in 5 mL of dichloromethane at room temperature overnight. Add some water and extract in dichloromethane. Wash organic layer with saturated aq. sodium chloride. Dry over anhydrous sodium sulfate and concentrate under reduced pressure. Subject residue to silica gel chromatography eluting with hexanes/ethyl acetate as eluent (30%-70%). LCMS ES+(m/z) 675 [M+H].

後処理

  1. extractionextract in dichloromethane
  2. dry with materialDry over anhydrous sodium sulfate
  3. concentrationconcentrate under reduced pressure
  4. washSubject residue to silica gel chromatography eluting with hexanes/ethyl acetate as eluent (30%-70%)

出典と根拠

ORDレコード
ord-26eeb220cc1f4a39b9e5d2fe1f054241
出典データセット
uspto-grants-2009_09
特許番号
US07582638B2

反応ノート

読み込み中…