Diisopropylethylamine → 2-(2-bromo-acetylamino)-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide

HRID 2388971ノート

反応式

HRID 2388971 の反応式
[NH2:1][C:2]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]3[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[N:20][N:19]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:16]3=[N:17][CH:18]=2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].C(N(C(C)C)CC)(C)C.[Br:47][CH2:48][C:49](Cl)=[O:50]>ClCCl>[Br:47][CH2:48][C:49]([NH:1][C:2]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]3[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[N:20][N:19]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:16]3=[N:17][CH:18]=2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5])=[O:50]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 89602Bromoacetyl chlorideHCID 579757432-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide

生成物 1

HCID 579758972-(2-bromo-acetylamino)-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide収率 87.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

285 mg (0.55 mmol) of 2-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide was dissolved in 25 mL of dichloromethane. 175 μL (132 mg, 1.02 mmol) of di-iso-propylethylamine was added and the solution cooled to 0° C. 110 μL (208 mg, 1.32 mmol) of bromoacetyl chloride was added in two portions within 2 h while stirring at 0° C. Upon complete addition the mixture was stirred for 19 h, allowing to warm to ambient temperature. The resulting solution was evaporated and the residue directly purified by flash chromatography on silica gel using a gradient of ethyl acetate containing 15% of methanol in hexanes to afford 306 mg (0.48 mmol, 87%) of 2-(2-bromo-acetylamino)-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide as a tan solid. MS: m/z 637.9+640.0 (M+H+).

後処理

  1. additionUpon complete addition the mixture
  2. stirringwas stirred for 19 h
  3. temperatureto warm to ambient temperature
  4. customThe resulting solution was evaporated
  5. customthe residue directly purified by flash chromatography on silica gel using a gradient of ethyl acetate containing 15% of methanol in hexanes

出典と根拠

ORDレコード
ord-0c1aced912a7442186622ab6cc9eb315
出典データセット
uspto-grants-2012_09
特許番号
US08268994B2

反応ノート

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