Optimization of the Synthetic Process of Antineoplastic Drug Dacarbazine

doi:10.6023/cjoc201410026

Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (5): 1161-1165.DOI: 10.6023/cjoc201410026 Previous Articles Next Articles

Notes

抗癌药物达卡巴嗪的合成工艺优化

肖胜伟^a, 刘志军^a, 柳杨^a, 陈河如^a,b

a 暨南大学药学院中药及天然药物研究所广州 510632;
b 广东省中药药效物质基础及创新药物研究重点实验室广州 510632

收稿日期:2014-10-18 修回日期:2014-12-19 发布日期:2015-01-07
通讯作者: 陈河如 E-mail:thrchen@jnu.edu.cn
基金资助:
国家自然科学基金(No.81172982)资助项目.

Optimization of the Synthetic Process of Antineoplastic Drug Dacarbazine

Xiao Shengwei^a, Liu Zhijun^a, Liu Yang^a, Chen Heru^a,b

a Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632;
b Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632

Received:2014-10-18 Revised:2014-12-19 Published:2015-01-07
Supported by:
Project supported by the National Natural Science Foundation of China (No.81172982).

1. Optimization of the Synthetic Process of Antineoplastic Drug Dacarbazine.PDF(470KB)

Abstract

Dacarbazine has been prepared started from glycine, which was carried on firstly through a four-step process including esterification, formylation, dehydration, amidation to give 2-isocyanoacetamide with a total yield of 42.9%. 2-Isocyanoacetamide was then cyclized with cyanamide under basic condition to afford the important intermediate 5-amino-1H-imidazole-4-carboxamide with yield of 68.2%. This intermediate undergoing diazotization and following coupling reaction with dimethylamine led to the target compound. The overall yield was 22.3%. All the intermediates and the target products dacarbazine were confirmed by ¹H NMR, ¹³C NMR and ESI-MS. The current process is economic efficient charac-terized by applied cheap materials, mild conditions, and good overall yield.

Key words: dacarbazine, process optimization, drug synthesis, anticancer

Cite this article

Xiao Shengwei, Liu Zhijun, Liu Yang, Chen Heru. Optimization of the Synthetic Process of Antineoplastic Drug Dacarbazine[J]. Chin. J. Org. Chem., 2015, 35(5): 1161-1165.

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抗癌药物达卡巴嗪的合成工艺优化

Optimization of the Synthetic Process of Antineoplastic Drug Dacarbazine

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