N,N'-羰基二咪唑 → 利伐沙班

HRID 241237笔记

反应方程式

HRID 241237 反应方程式
[OH:1][C@H:2]([CH2:13][NH:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][C:22]2=[O:27])=[CH:17][CH:16]=1)[CH2:3][NH:4][C:5]([C:7]1[S:8][C:9]([Cl:12])=[CH:10][CH:11]=1)=[O:6].[C:28](N1C=CN=C1)(N1C=CN=C1)=[O:29]>C1(C)C=CC=CC=1.CN1CCCC1=O>[Cl:12][C:9]1[S:8][C:7]([C:5]([NH:4][CH2:3][C@@H:2]2[O:1][C:28](=[O:29])[N:14]([C:15]3[CH:16]=[CH:17][C:18]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][C:22]4=[O:27])=[CH:19][CH:20]=3)[CH2:13]2)=[O:6])=[CH:11][CH:10]=1

参与物

5

反应物 2

HCID 68263N,N'-羰基二咪唑HCID 10001574利伐沙班杂质G

产物 1

HCID 9875401利伐沙班收率 90%

试剂、催化剂与溶剂 2

HCID 1140甲苯溶剂HCID 13387甲基吡咯烷酮溶剂

反应条件

温度
80 °C

实验过程

Under an atmosphere of nitrogen to a suspension of 14.85 g of 5-chlorothiophen-2-carboxylic acid-{(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl}amide (MW=409.89; 1 eq.) in 145 mL toluene and 22 mL N-methylpyrrolidone were added 7.13 g (MW=162.15; 1.2 eq.) of 1,1′-carbonyldiimidazol. The reaction mixture was heated to 80° C. After stirring for 30 minutes the mixture was heated to 110° C. and stirred at this temperature for 2 hours. Then the mixture was cooled to 22° C. After stirring for 1 hour at ambient temperature the product was isolated by filtration and washed with 60 mL of toluene and 60 mL of water. The wet product was dried at 30° C. in vacuo to yield 15.99 g (MW=435.89; 1.013 eq.) of the title compound (90% of theory).

后处理

  1. temperaturewas heated to 110° C.
  2. stirringstirred at this temperature for 2 hours
  3. temperatureThen the mixture was cooled to 22° C
  4. stirringAfter stirring for 1 hour at ambient temperature the product
  5. customwas isolated by filtration
  6. washwashed with 60 mL of toluene and 60 mL of water
  7. customThe wet product was dried at 30° C. in vacuo

来源与证据

ORD记录
ord-3b237dcc19b34c4786590ad77ba784a8
来源数据集
uspto-grants-2014_02
专利号
US08648189B2

反应笔记

加载中…