Synthese von 4-halogensubstituierten Analogen von Trimethoprim

✍ Scribed by Ivan Kompis; Alexander Wick

• Publisher: John Wiley and Sons
• Year: 1977
• Tongue: German
• Weight: 521 KB
• Volume: 60
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19770600854

✦ Synopsis

The Synthesis of 4‐Halogen‐substituted Analogs of Trimethoprim

The four 2,4‐diamino‐5‐(4‐halo‐3,5‐dimethoxybenzyl)pyrimidines 20a‐d have been synthesized along known routes, i.e. form the corresponding aldehydes 17a‐d via the aminomethylidene‐derivatives 18a‐d and 19a‐d, respectively (Scheme 4). All four aldehydes were prepared from a common intermediate, methyl 4‐amino‐3,5‐dimethoxybenzoate (3), which was obtained from dimethyl 2,6‐dimethoxyterephthalate (2) and hydroxylamine in a regioselective Lossen‐type rearrangement mediated by polyphosphoric acid (Scheme 1). Under identical rearrangement conditions 2,6‐diethoxyterephthalate (12) led, in addition to the amine 14, to the benzoxazolone 15 (Scheme 2). Scope and mechanism of this reaction are discussed. ‐ The antimicrobial activity of the diamino‐pyrimidines 20a‐d, expressed as the inhibition of E. coli‐dihydrofolate reductase, has been measured and compared with that of trimethoprim (1), an established antimicrobial agent.