Methyl iodide → 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

HRID 246165ノート

反応式

HRID 246165 の反応式
[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([Cl:28])=[CH:24][C:25]=4[F:27])[NH:20][N:19]=3)[N:16]=2)[N:11]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:10]=1)=[O:8])[CH3:5].[H-].[Na+].I[CH3:40]>CN(C=O)C>[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[C:26]4[C:21](=[CH:22][C:23]([Cl:28])=[CH:24][C:25]=4[F:27])[N:20]([CH3:40])[N:19]=3)[N:16]=2)[N:11]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:34])([CH3:36])[CH3:35])[CH:10]=1)=[O:8])[CH3:5]

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 712860522-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

生成物 1

HCID 712883412-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide収率 33.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

A 50 mL round-bottomed flask was charged with 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide (120 mg, 0.225 mmol) and DMF (0.45 ml) to give a light yellow solution. The reaction mixture was placed under argon atmosphere and cooled in a 0° C. bath. NaH (60% in mineral oil, 23 mg, 0.575 mmol) was added. The reaction mixture was stirred at 0° C. for 10 min and at room temperature for 10 min then returned to the cooling bath and iodomethane (21 μl, 0.34 mmol) was added. The reaction was stirred at 0° C. for 10 min then the bath was removed and stirring continued at room temperature for an additional 18 h. The reaction was quenched with water and the precipitate collected by filtration. The crude material was purified by chromoatography over SiO2 with EtOAc/heptane (gradient: 0-100% EtOAc) to afford 41 mg (33%) of 2-(6-chloro-4-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as an off-white solid. MS: [M+H]+=547.

後処理

  1. customto give a light yellow solution
  2. additionwas added
  3. stirringThe reaction was stirred at 0° C. for 10 min
  4. customthe bath was removed
  5. stirringstirring
  6. waitcontinued at room temperature for an additional 18 h
  7. customThe reaction was quenched with water
  8. filtrationthe precipitate collected by filtration
  9. customThe crude material was purified by chromoatography over SiO2 with EtOAc/heptane (gradient: 0-100% EtOAc)

出典と根拠

ORDレコード
ord-f460a45d1ac64bd48fab28c0be2ef867
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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