药物详细合成路线
| Name | CMDA | | Chemical Name | 4-[N-(2-Chloroethyl)-N-[2-(mesyloxy)ethyl]amino]benzoyl-L-glutamic acid | | CAS | 122665-73-0 | | Related CAS | | | Formula | C17H23ClN2O8S | | Structure |  | | Formula Weight | 450.89846 | | Stage | I 期临床 | | Company | Institute of Cancer Research (Originator) | | Activity/Mechanism | Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, ONCOLYTIC DRUGS, DNA-Damaging Drugs | | Syn. Route | 1 | | Route 1 | | the synthesis of cmda (vii) was accomplished using a modified version of the published procedures:the di-tert-butyl 4-nitrobenzoyl-l-glutamate (ii) was reduced to di-tert-butyl 4-aminobenzoyl-l-glutamate (iii) using transfer hydrogenation. the reductive amination of (iii) with chloroethanal yielded the monofunctional di-tert-butyl 4-[(2-chloroethyl)amino]benzoyl-l-glutamate (iv), which was n-alkylated with ethylene oxide to give di-tert-butyl 4-[(2-chloroethyl)(2-hydroxyethyl)amino]benzoyl-l-glutamate (v). reaction of (v) with methanesulfonyl chloride at 5 c yielded di-tert-butyl 4-[(2-chloroethyl)[2-(mesyloxy)ethyl]amino]benzoyl-l-glutamate (vi). treatment of (vi) with formic acid followed by lyophilization gave the diacid, 4-[(2-chloroethyl)[2-(mesyloxy)ethyl]amino]benzoyl-l-glutamic acid (vii). | | |  | | List of intermediates | No. | | methyl decanoate | (ii) | | dimethyl 2-oxoundecylphosphonate | (iii) | | dimethyl 1-diazo-2-oxoundecylphosphonate | (iv) | | dimethyl (1s,2r)-2-hexyl-5-oxocyclopentylphosphonate | (v) | | methyl 7-(2-hexyl-5-oxocyclopentylidene)heptanoate | (vi) | | methyl 7-[(1r,2s)-2-hexyl-5-oxocyclopentyl]heptanoate | (vii) | | 5-hydroxy-2,4-dimethyl-8-[[2-(1h-1,2,3,4-tetraazol-5-yl)[1,1-biphenyl]-4-yl]methyl]-5,8-dihydropyrido[2,3-d]pyrimidin-7(6h)-one | (viii) | | 1-[(e)-3-chloro-1-propenyl]-3-methoxy-2-nitrobenzene; 3-[(e)-3-chloro-1-propenyl]-2-nitrophenyl methyl ether | (i) | | | Reference 1: springer, c.j.; mann, j.; bagshawe, k.d.; haase-held, m.; synthesis of an n-mustard prodrug. tetrahedron 1990, 46, 5377-82. Reference 2: antoniw, p.; bisset, g.m.f.; springer, c.j.; searle, f.; jarman, m.; bagshawe, k.d.; novel prodrugs which are activated to cytotoxic alkylating agents by carboxypeptidase g2. j med chem 1990, 33, 2, 677-81. Reference 3: springer, c.j.; cmda. drugs fut 1993, 18, 3, 212. |
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来源:药化网
作者:药化小编
摘要:本文合成路线介绍的是药物中文名CMDA；英文名CMDA；CAS[122665-73-0]
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