【结 构 式】 |
【分子编号】32091 【品名】[Nalpha-(3-Methylquinolin-8-ylsulfonyl)-Nomega-nitro-L-arginyl]-4(R)-methylpiperidine-2(R)-carboxylic acid; 1-[N(G)-Nitro-N2-(3-methyl-8-quinolinylsulfonyl)-L-arginyl]-4-methyl-2-piperidinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C23H31N7O7S 【 分 子 量 】549.60812 【元素组成】C 50.26% H 5.69% N 17.84% O 20.38% S 5.83% |
合成路线1
该中间体在本合成路线中的序号:(VII)The condensation of N(G)-nitro-N2-(tert-butoxy-carbonyl)-L-arginine (I) with ethyl 4-methylpiperidine-2-carboxylate (II) by means of isobutyl chloroformate (A) and triethylamine in THF gives ethyl 1-[N(G)-nitro-N2-(tert-butoxycarbonyl)-L-arginyl]-4-methylpiperidine-2-carboxylate (III), which is protected with HCl in ethyl acetate yielding ethyl 1-(N(G)-nitro-L-arginyl)-4-methylpiperidine-2-carboxylate (IV). The condensation of (IV) with 3-methylquinoline-8-sulfonyl chloride (V) by means of triethylamine in chloroform affords ethyl 1-(N(G)-nitro-N2-(3-methyl-8-quinolinylsulfonyl)-L-arginyl]-4-methyl-2-piperidinecarboxylate (VI), which is hydrolyzed with NaOH in ethanol-water giving 1-[N(G)-nitro-N2-(3-methyl-8-quinolinylsulfonyl)-L-arginyl]-4-methyl-2-piperidinecarboxylic acid (VII). Finally, this compound is deprotected and reduced by hydrogenation with H2 over Pd/C in ethanol.
【1】 Kikumoto, R.; Tamao, Y.; Onkubo, K.; Tezuka, T.; Tonomura, S.; Hihikata, A.; Okamoto, S. (Mitsubishi Chemical Corp.); N2-Arylsulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof. US 4201863 . |
【2】 Kikumoto, R.; Tamao, Y.; Onkubo, K.; Tezuka, T.; Tonomura, S.; Hihikata, A.; Okamoto, S. (Mitsubishi Chemical Corp.); N2-Arylsulfonyl-L-argininamides and the pharmaceutically acceptable salts thereof. EP 0008746; US 4258192 . |
【3】 Castaner, J.; Grau, M.; Blancafort, P.; Serradell, M.N.; MD-805. Drugs Fut 1982, 7, 11, 810. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 13423 | 1-[(Chlorocarbonyl)oxy]-2-methylpropane; Isobutyl chloroformate;isobutyl carbonochloridate | 543-27-1 | C5H9ClO2 | 详情 | 详情 |
(I) | 32085 | N(G)-nitro-N2-(tert-butoxy-carbonyl)-L-arginine; Nalpha-(tert-butoxycarbonyl)-Nomega-nitro-L-arginine | C11H21N5O6 | 详情 | 详情 | |
(II) | 32086 | Ethyl (2R,4R)-4-methyl-2-piperidinecarboxylate | C9H17NO2 | 详情 | 详情 | |
(III) | 32087 | Ethyl 1-[N(G)-nitro-N2-(tert-butoxycarbonyl)-L-arginyl]-4-methylpiperidine-2-carboxylate; [Nalpha-(tert-butoxycarbonyl)-Nomega-nitro-L-arginyl]-4(R)-methylpiperidine-2(R)-carboxylic acid ethyl ester | C20H36N6O7 | 详情 | 详情 | |
(IV) | 32088 | 1-(N-omega-nitro-L-arginyl)-4(R)-methylpiperidine-2(R)-carboxylic acid ethyl ester; Ethyl 1-(N(G)-nitro-L-arginyl)-4-methylpiperidine-2-carboxylate | C15H28N6O5 | 详情 | 详情 | |
(V) | 32089 | 3-methylquinoline-8-suIfonyl chloride; 3-methyl-8-quinolinesulfonyl chloride | C10H8ClNO2S | 详情 | 详情 | |
(VI) | 32090 | Ethyl 1-(N(G)-nitro-N2-(3-methyl-8-quinolinylsulfonyl)-L-arginyl]-4-methyl-2-piperidinecarboxylate; [Nalpha-(3-Methylquinolin-8-ylsulfonyl)-Nomega-nitro-L-arginyl]-4(R)-methylpiperidine-2(R)-carboxylic acid ethyl ester | C25H35N7O7S | 详情 | 详情 | |
(VII) | 32091 | [Nalpha-(3-Methylquinolin-8-ylsulfonyl)-Nomega-nitro-L-arginyl]-4(R)-methylpiperidine-2(R)-carboxylic acid; 1-[N(G)-Nitro-N2-(3-methyl-8-quinolinylsulfonyl)-L-arginyl]-4-methyl-2-piperidinecarboxylic acid | C23H31N7O7S | 详情 | 详情 |