文献类型：期刊文献

英文题名：Practical Preparation of Trimethoprim: A Classical Antibacterial Agent

作者：Ji, Ya-Fei[1,2];Jiang, Jian-An[1];Liu, Hong-Wei[1];Liao, Dao-Hua[1];Wei, Xian-Yong[2]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[2]China Univ Min & Technol, Sch Chem Engn, Xuzhou 221008, Peoples R China

年份：2013

卷号：43

期号：11

起止页码：1517

外文期刊名：SYNTHETIC COMMUNICATIONS

收录：;EI(收录号：20242716638250);WOS:【SCI-EXPANDED(收录号:WOS:000322302400007)，CCR-EXPANDED(收录号:WOS:000322302400007)】；

基金：We thank the National Natural Science Foundation of China (Project No. 21176074) and Shandong Haoyuan Co. Ltd. for financial support.

语种：英文

外文关键词：Antibacterial agent; highly effective preparation; trimethoprim; 3; 4; 5-trimethoxybenzaldehyde

摘要：An efficient, simple, and mild preparation of the classical antibacterial agent trimethoprim (1) was achieved in 85% overall yield from 3,4,5-trimethoxybenzaldehyde (2). First, the addition of propenenitrile (3) with dimethylamine almost quantitatively afforded 3-dimethylaminopropanenitrile (7). Then, by condensation of 7 with 2 as well as the continuous replacement of 3-dimethylamino group with aniline in situ, the key intermediate 3-anilino-2-(3,4,5-trimethoxybenzyl)propenenitrile (9) was obtained in an excellent yield of 91% with a one-pot procedure. Finally, the cyclization of 9 with guanidine nitrate furnished 1 in yields as good as 95% in the presence of the excessive sodium methoxide. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) to view the free supplemental file.