Synthesis of substituted 2-amino-4-quinazolinones via ortho-fluorobenzoyl guanidines

A novel route to 12 substituted 2-amino-4-quinazolinones is described. Starting from 2,6-difluoro-4-methoxybenzonitrile, substitution of one of the fluorine atoms either directly or indirectly with heterocycles (e.g., pyridyl, thiazolyl, pyrazolyl) followed by hydrolysis of the nitrile gave a series of o-fluorobenzoic acid derivatives. Condensation with a set of six N,N-disubstituted guanidines followed by base-promoted ring closure afforded 2-amino-4-quinazolinone derivatives.