2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 2. C-Alkylation of pyrimidines with Mannich bases and application to the synthesis of trimethoprim and analogues.
A new route to 5-(p-hydroxybenzyl)pyrimidines has been developed which utilizes phenolic Mannich bases plus pyrimidines containing at least two activating groups. The products can be alkylated on the phenolic oxygen or on the pyrimidine N-1 atom, depending on conditions. This method has been used to prepare trimethoprim, a broad-spectrum antibacterial agent, starting from 2,4-diaminopyrimidine and 2,6-dimethoxyphenol.
D000478:Alkylation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001419:Bacteria / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D005493:Folic Acid Antagonists; D066298:In Vitro Techniques; D008352:Mannich Bases; D008826:Microbial Sensitivity Tests; D051381:Rats; D013329:Structure-Activity Relationship; D014295:Trimethoprim / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D005493:Folic Acid Antagonists; D008352:Mannich Bases; D014295:Trimethoprim