Water → ethyl 3-(2-((4-(N-(hexyloxycarbonyl)carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate

HRID 1470520

反応式

HRID 1470520 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[C:8]([C:10]1[CH:30]=[CH:29][C:13]2[N:14]([CH3:28])[C:15]([CH2:17][NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25](=[NH:27])[NH2:26])=[CH:21][CH:20]=3)=[N:16][C:12]=2[CH:11]=1)=[O:9].O.C(=O)([O-])[O-].[K+].[K+].N1([C:50]([O:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH3:58])=[O:51])C=CN=C1>C(#N)C>[CH3:58][CH2:57][CH2:56][CH2:55][CH2:54][CH2:53][O:52][C:50](/[N:27]=[C:25](\[NH2:26])/[C:22]1[CH:21]=[CH:20][C:19]([NH:18][CH2:17][C:15]2[N:14]([CH3:28])[C:13]3[CH:29]=[CH:30][C:10]([C:8]([N:7]([C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[O:9])=[CH:11][C:12]=3[N:16]=2)=[CH:24][CH:23]=1)=[O:51]

参加物

6

反応物 4

HCID 962Water2 回HCID 11430Potassium CarbonateHCID 446804Dabigatran Ethyl EsterHCID 57389745hexyl 1H-imidazole-1-carboxylate

生成物 1

HCID 6445226ethyl 3-(2-((4-(N-(hexyloxycarbonyl)carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒2 回

反応条件

温度
15 °C

実験手順

1-methyl-2-[N-[4-amidinophenyl]aminomethyl]benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide compound of formula-5 (100 g) was added to acetonitrile (1200 ml) and water (800 ml) at 25-35° C. and then cooled to 12-18° C. Potassium carbonate (138 g) was added to the reaction mixture and stirred for 15 minutes at 12-18° C. A solution of hexyl 1H-imidazole-1-carboxylate compound of formula-4 (66 g) in acetonitrile (150 ml) was slowly added to the reaction mixture over a period of 25 minutes at 12-18° C. and stirred for 14 hours at 15-20° C. After completion of the reaction, water was added to the reaction mixture and stirred for 30 minutes. Filtered the solid, washed with acetonitrile followed by aqueous acetonitrile and then dried to get title compound. Dichloromethane was added to the obtained compound and stirred for 15 minutes. Water was added to the reaction mixture and stirred for 20 minutes at 25-35° C. Both the organic and aqueous layers were separated, and the dichloromethane layer was washed with water followed by sodium chloride and then distilled off completely under reduced pressure. Acetone (600 ml) was added to the obtained residue and stirred for 45 minutes at 25-35° C. to obtain a clear solution. Water (500 ml) was added to the obtained solution and stirred for 45 minutes at 25-35° C. to get the solid. Filtered the solid, washed with water and finally with methyl tertiary butyl ether and then dried to get the pure title compound. Further the obtained solid recrystallized from ethylacetate and ethanol.

後処理

  1. stirringstirred for 14 hours at 15-20° C
  2. additionwas added to the reaction mixture
  3. stirringstirred for 30 minutes
  4. filtrationFiltered the solid
  5. washwashed with acetonitrile
  6. customdried

出典と根拠

ORDレコード
ord-689d4d2772884e1abc3a7604ee0bb8ed
出典データセット
uspto-grants-2015_04
特許番号
US09006448B2

関連ノート

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