【结 构 式】 |
【分子编号】60798 【品名】ethyl 3-[({2-[(4-cyanoanilino)methyl]-1-methyl-1H-benzimidazol-5-yl}carbonyl)(2-pyridinyl)amino]propanoate 【CA登记号】 |
【 分 子 式 】C27H26N6O3 【 分 子 量 】482.54208 【元素组成】C 67.21% H 5.43% N 17.42% O 9.95% |
合成路线1
该中间体在本合成路线中的序号:(VII)4-Methylamino-3-nitrobenzoic acid (I) is converted into acid chloride (II) by using SOCl2, and subsequently condensed with ethyl 3-(2-pyridylamino)propionate (III) to produce amide (IV). Reduction of the nitro group of (IV) by catalytic hydrogenation yields the phenylenediamine (V). After acylation of diamine (V) with N-(4-cyanophenyl)glycine (VI), cyclization of the resulting amino amide in refluxing AcOH leads to benzimidazole (VII). The cyano group of (VII) is then transformed into amidine (VIII) employing the Pinner reaction. Finally, acylation of the amidino group of (VIII) with hexyl chloroformate gives rise to the target amidine carbamate derivative
【1】 Hauel, N.H.; et al.; Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem 2002, 45, 9, 1757. |
【2】 Hauel, N.; Wienen, W.; Ries, U.; Priepke, H.; Stassen, J.M. (Boehringer Ingelheim Pharma KG); Disubstd. bicyclic heterocycles, their production and use as medicaments. DE 19706229; DE 19751939; EP 0966454; JP 2001509815; US 2003004181; US 6087380; US 6469039; WO 9837075 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 60793 | 4-(methylamino)-3-nitrobenzoic acid | C8H8N2O4 | 详情 | 详情 | |
(II) | 60794 | 4-(methylamino)-3-nitrobenzoyl chloride | C8H7ClN2O3 | 详情 | 详情 | |
(III) | 60795 | ethyl 3-(2-pyridinylamino)propanoate | C10H14N2O2 | 详情 | 详情 | |
(IV) | 60796 | ethyl 3-[[4-(methylamino)-3-nitrobenzoyl](2-pyridinyl)amino]propanoate | C18H20N4O5 | 详情 | 详情 | |
(V) | 60797 | ethyl 3-[[3-amino-4-(methylamino)benzoyl](2-pyridinyl)amino]propanoate | C18H22N4O3 | 详情 | 详情 | |
(VI) | 51512 | 2-(4-cyanoanilino)acetic acid | C9H8N2O2 | 详情 | 详情 | |
(VII) | 60798 | ethyl 3-[({2-[(4-cyanoanilino)methyl]-1-methyl-1H-benzimidazol-5-yl}carbonyl)(2-pyridinyl)amino]propanoate | C27H26N6O3 | 详情 | 详情 | |
(VIII) | 60799 | ethyl 3-[{[2-({4-[amino(imino)methyl]anilino}methyl)-1-methyl-1H-benzimidazol-5-yl]carbonyl}(2-pyridinyl)amino]propanoate | C27H29N7O3 | 详情 | 详情 |