氢化钠 → 2-(5-difluoromethoxy-1-pyridin-3-ylmethyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246306

反应方程式

HRID 246306 反应方程式
[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:29])[F:28])[CH:24]=4)[NH:19][N:18]=3)[N:15]=2)[N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br.Br[CH2:42][C:43]1[CH:44]=[N:45][CH:46]=[CH:47][CH:48]=1>CN(C=O)C>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH:27]([F:28])[F:29])[CH:24]=4)[N:19]([CH2:42][C:43]4[CH:44]=[N:45][CH:46]=[CH:47][CH:48]=4)[N:18]=3)[N:15]=2)[N:10]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参与物

5

反应物 3

HCID 24758氢化钠HCID 127070373-(溴甲基)吡啶HCID 712795662-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

产物 1

HCID 712807112-(5-difluoromethoxy-1-pyridin-3-ylmethyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide收率 90%

试剂、催化剂与溶剂 1

HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
0 °C

实验过程

In a 25 ml round-bottomed flask, 2-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (120 mg, 0.23 mmol) was dissolved in DMF (1.7 ml). The light yellow solution was cooled to 0° C. and sodium hydride (60% in mineral oil, 37 mg, 0.93 mmol) was added. The reaction was stirred at 0° C. for 15 min then 3-(bromomethyl)pyridine hydrobromide (91 mg, 0.36 mmol) was added. The reaction mixture was stirred at 0° C. for 1 h then quenched with water and diluted with petroleum ether. The suspension was filtered, washed with water and petroleum ether and the product collected was dried under high vacuum to afford 126 mg (90%) of 2-(5-difluoromethoxy-1-pyridin-3-ylmethyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a yellow powder.

后处理

  1. stirringThe reaction mixture was stirred at 0° C. for 1 h
  2. customthen quenched with water
  3. additiondiluted with petroleum ether
  4. filtrationThe suspension was filtered
  5. washwashed with water and petroleum ether
  6. customthe product collected
  7. customwas dried under high vacuum

来源与证据

ORD记录
ord-2f62d447a62141799ffeb7339ac01f45
来源数据集
uspto-grants-2014_02
专利号
US08658646B2

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