Sodium Cyanide → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyanomethyl-oxazol-2-yl)-ethyl]-amide

HRID 245943ノート

反応式

HRID 245943 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:23][C@@H:24]([C:26]5[O:27][CH:28]=[C:29]([CH2:31]OS(C)(=O)=O)[N:30]=5)[CH3:25])=[O:22])=[CH:19][N:18]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[C-:45]#[N:46].[Na+]>CN(C=O)C>[C:45]([CH2:31][C:29]1[N:30]=[C:26]([C@H:24]([NH:23][C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([F:1])=[CH:3][CH:4]=5)[N:8]([CH3:11])[N:7]=4)[N:13]=3)[N:18]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:42])([CH3:44])[CH3:43])[CH:19]=2)=[O:22])[CH3:25])[O:27][CH:28]=1)#[N:46]

参加物

4

反応物 2

HCID 8929Sodium CyanideHCID 86677925methanesulfonic acid 2-((R)-1-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-ethyl)-oxazol-4-ylmethyl ester

生成物 1

HCID 712888822-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyanomethyl-oxazol-2-yl)-ethyl]-amide収率 36%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

In a round-bottomed flask, methanesulfonic acid 2-((R)-1-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-ethyl)-oxazol-4-ylmethyl ester (146 mg, 0.18 mmol) was dissolved in DMF (0.5 ml). Sodium cyanide (27 mg, 0.55 mmol) was added and the reaction mixture was stirred at 80° C. overnight. The reaction was cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-60% EtOAc) to isolate 37 mg (36%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyanomethyl-oxazol-2-yl)-ethyl]-amide as a yellow solid.

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with water
  3. extractionextracted with diethyl ether (2×)
  4. washThe combined organic layers were washed twice with water and once with brine
  5. dry with materialthen dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-60% EtOAc)

出典と根拠

ORDレコード
ord-f4c71d3a77a3479c80ddd8742fbf73f2
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…