1,1'-Carbonyldiimidazole → Rivaroxaban

HRID 241237ノート

反応式

HRID 241237 の反応式
[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

参加物

5

反応物 2

HCID 682631,1'-CarbonyldiimidazoleHCID 100015745-Chloro-N-((2R)-2-hydroxy-3-((4-(3-oxo-4-morpholinyl)phenyl)amino)propyl)-2-thiophenecarboxamide

生成物 1

HCID 9875401Rivaroxaban収率 90%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-3b237dcc19b34c4786590ad77ba784a8
出典データセット
uspto-grants-2014_02
特許番号
US08648189B2

反応ノート

読み込み中…