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 1527138노트

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HRID 1527138 반응식
[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]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 22466Hexyl chloroformate2회HCID 446804Dabigatran Ethyl Ester

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

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.

출처 및 근거

ORD 기록
ord-8e829d8da87148349c67ef723f155bce
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09086390B2

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