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

HRID 1527138ノート

反応式

HRID 1527138 の反応式
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[CH:19][C:20]([C:22]([N:24]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:23])=[CH:21][C:14]=3[N:13]=2)=[CH:6][CH:5]=1)(=[NH:3])[NH2:2].Cl[C:39]([O:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH3:47])=[O:40].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.O>[CH3:47][CH2:46][CH2:45][CH2:44][CH2:43][CH2:42][O:41][C:39](/[N:3]=[C:1](\[NH2:2])/[C:4]1[CH:5]=[CH:6][C:7]([NH:10][CH2:11][C:12]2[N:16]([CH3:17])[C:15]3[CH:18]=[CH:19][C:20]([C:22]([N:24]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=4)[CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:23])=[CH:21][C:14]=3[N:13]=2)=[CH:8][CH:9]=1)=[O:40]

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 22466Hexyl chloroformate2 回HCID 446804Dabigatran Ethyl Ester

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 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Dabigatran etexilate was first described in U.S. Pat. No. 6,087,380, according to which the synthesis of dabigatran etexilate was carried out in three synthetic steps (see Scheme 1). Example 58 describes the condensation between ethyl 3-{[3-amino-4-(methylamino)benzoyl](pyridin-2-yl)amino}propanoate (compound II) and N-(4-cyanophenyl)glycine (compound III) in the presence of N,N′-carbonyldiimidazole (CDI) in tetrahydrofuran to give the hydrochloride salt of ethyl 3-{[(2-{[(4-cyanophenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl](pyridin-2-yl)amino}propanoate (compound IV), which is subsequently reacted with ethanolic hydrochloric acid, ethanol and ammonium carbonate to give the hydrochloride salt of ethyl 3-{[(2-[{(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl](pyridin-2-yl)amino}propanoate (compound V). Finally, example 113 describes the reaction between compound V and n-hexyl chloroformate (compound VI), in the presence of potassium carbonate, in a mixture of tetrahydrofuran and water, to give dabigatran etexilate after work-up and chromatographic purification. However, no information is given about the purity of the isolated dabigatran etexilate.

出典と根拠

ORDレコード
ord-8e829d8da87148349c67ef723f155bce
出典データセット
uspto-grants-2015_07
特許番号
US09086390B2

反応ノート

読み込み中…