【结 构 式】 |
【分子编号】51511 【品名】[1-[3-amino-4-(methylamino)phenyl]cyclopropyl](1-pyrrolidinyl)methanone 【CA登记号】 |
【 分 子 式 】C15H21N3O 【 分 子 量 】259.35136 【元素组成】C 69.47% H 8.16% N 16.2% O 6.17% |
合成路线1
该中间体在本合成路线中的序号:(VI)Nitration of 1-(4-chlorophenyl)-1-cyclopropanecarboxylic acid (I) with fuming HNO3 produced the 3-nitro derivative (II). The chloride group of (III) was then displaced with methylamine to give the nitro aniline (III). Coupling of (III) with pyrrolidine (IV) by means of TBTU yielded amide (V). The nitro group of (V) was reduced by catalytic hydrogenation over Pd/C to afford the phenylenediamine (VI), which was subsequently acylated by N-(4-cyanophenyl)glycine (VII), yielding amide (VIII). Benzimidazole (IX) was then obtained by cyclization of (VIII) in refluxing HOAc. Pinner reaction of nitrile (IX) with ethanolic HCl produced the imidate (X), which was finally converted to the target amidine by treatment with ammonium carbonate.
【1】 Kauffmann, I.; Ries, U.; Priepke, H.; Hauel, N.; Stassen, J.M.; Nar, H.; Wienen, W. (Boehringer Ingelheim Pharma KG); Benzimidazoles, production thereof and use thereof as medicaments. DE 19829964; EP 1095025; WO 0001704 . |
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) | 51507 | 1-(4-Chlorophenyl)-1-cyclopropanecarboxylic acid | 72934-37-3 | C10H9ClO2 | 详情 | 详情 |
(II) | 51508 | 1-(4-chloro-3-nitrophenyl)cyclopropanecarboxylic acid | C10H8ClNO4 | 详情 | 详情 | |
(III) | 51509 | 1-[4-(methylamino)-3-nitrophenyl]cyclopropanecarboxylic acid | C11H12N2O4 | 详情 | 详情 | |
(IV) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
(V) | 51510 | [1-[4-(methylamino)-3-nitrophenyl]cyclopropyl](1-pyrrolidinyl)methanone | C15H19N3O3 | 详情 | 详情 | |
(VI) | 51511 | [1-[3-amino-4-(methylamino)phenyl]cyclopropyl](1-pyrrolidinyl)methanone | C15H21N3O | 详情 | 详情 | |
(VII) | 51512 | 2-(4-cyanoanilino)acetic acid | C9H8N2O2 | 详情 | 详情 | |
(VIII) | 51513 | 2-(4-cyanoanilino)-N-[2-(methylamino)-5-[1-(1-pyrrolidinylcarbonyl)cyclopropyl]phenyl]acetamide | C24H27N5O2 | 详情 | 详情 | |
(IX) | 51514 | 4-[([1-methyl-5-[1-(1-pyrrolidinylcarbonyl)cyclopropyl]-1H-benzimidazol-2-yl]methyl)amino]benzonitrile | C24H25N5O | 详情 | 详情 | |
(X) | 51515 | ethyl 4-[([1-methyl-5-[1-(1-pyrrolidinylcarbonyl)cyclopropyl]-1H-benzimidazol-2-yl]methyl)amino]benzenecarboximidoate | C26H31N5O2 | 详情 | 详情 |