PURINES, PYRIMIDINES, AND IMIDAZOLES .53. SYNTHESIS OF SOME 5-HALOGENO-ANALOGUES OF METIAMIDE AND CIMETIDINE

Journal article

Ethyl 5-chloroimidazole-4-carboxylate has been prepared by diazotisation of ethyl 5-amino-1-(di-O-isopropylidene-α- or -α,β-D- mannofuranosyl)imidazole-4-carboxylate, reaction of the diazonium salt with copper(I) chloride and removal of the 1-substituent with hydrochloric acid, or by similar conversion of ethyl 5-amino-1-t-butylimidazole-4-carboxylate to ethyl 1-t-butyl-5-chloroimidazole 4-carboxylate, and removal of the t-butyl group with hydrogen bromide. Ethyl 5-fluoroimidazole-4-carboxylate has been prepared from ethyl 5-amino-1-t-butylimidazole-4-carboxylate by diazotisation and photolysis in the presence of tetrafluoroboric acid. Ethyl 5-chloroimidazole-4- carboxylate and ethyl 5-fluoroimidazole-4-carboxylate have been converted into the corresponding alcohols by reaction with lithium aluminium hydride. 5-Chloro-4-(hydroxymethyl)imidazole has also been prepared by electrolysis of 5-chloroimidazole-4-carboxylic acid at a mercury cathode. 5-Chloroimidazole has been converted into the 5-chloroimidazolyl analogues of metiamide and cimetidine by a sequence of reactions, and 5-fluoroimidazole has been similarly converted into the 5-fluoro-analogue of metiamide. The metiamide and cimetidine analogues were found to be histamine H 2-receptor antagonists.

Authors: Brown, T; Shaw, G; Durant, G

• Publication status: Published
• Journal: JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1
• Issue: 10
• Pages: 2310-2315
• Publication date: 1980-01-01
• DOI: 10.1039/p19800002310
• EISSN: 1364-5463
• ISSN: 0300-922X
• Language: English