CMDA [CAS:122665-73-0]合成路线图解

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.

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]