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N-(4-Cyanophenyl)glycine → Ethyl 3-(((2-(((4-cyanophenyl)amino)methyl)-1-methyl-1H-benzimidazol-5-yl)carbonyl)pyridin-2-ylamino)propionate

HRID 1527137
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HRID 1527137 반응식
CCCCCCOC(/[N:10]=[C:11](\N)/[C:12]1[CH:13]=[CH:14][C:15]([NH:18][CH2:19][C:20]2[N:28]([CH3:29])[C:27]3[CH:26]=[CH:25][C:24]([C:30]([N:32]([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][N:45]=4)[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:31])=[CH:23][C:22]=3[N:21]=2)=[CH:16][CH:17]=1)=O.NC1C=C(C=CC=1NC)C(N(C1C=CC=CN=1)CCC(OCC)=O)=O.C(C1C=CC(NCC(O)=O)=CC=1)#N>O1CCCC1>[C:11]([C:12]1[CH:17]=[CH:16][C:15]([NH:18][CH2:19][C:20]2[N:28]([CH3:29])[C:27]3[CH:26]=[CH:25][C:24]([C:30]([N:32]([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][N:45]=4)[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:31])=[CH:23][C:22]=3[N:21]=2)=[CH:14][CH:13]=1)#[N:10]
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참가 물질

5

반응물 3

HCID 817965N-(4-Cyanophenyl)glycine2회HCID 6445226ethyl 3-(2-((4-(N-(hexyloxycarbonyl)carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate2회HCID 11982993N-(3-Amino-4-(methylamino)benzoyl)-N-2-pyridinyl-beta-alanine ethyl ester2회

생성물 1

HCID 11627749Ethyl 3-(((2-(((4-cyanophenyl)amino)methyl)-1-methyl-1H-benzimidazol-5-yl)carbonyl)pyridin-2-ylamino)propionate

시약·촉매·용매 1

HCID 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-e8a39401a84c42a5a5b529ee3990287c
출처 데이터셋
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09086390B2

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