Process for preparing quinazolinone derivatives and their 2-(N-mono-substituted amino)-phenyl ketone intermediate derivatives

Claim 1

A process for producing quinazoline derivatives represented by the formula, ##STR7## wherein R 1 and R 2 are individually a hydrogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 alkoxy group, a nitro group, a trifluoromethyl group, a C 1 - C 4 alkylthio group, a C 1-C 4 alkylsulfonyl group or a halogen atom; R 3 is a phenyl group, a halophenyl group, a C 1 -C 4 alkylphenyl group, a C 1 - C 4 alkoxyphenyl group, a trifluoromethylphenyl group, a C 3 -C 6 cycloalkyl group, a C 5 -C 6 cycloalkenyl group, a pyridyl group, a furyl group, a thienyl group or a naphthyl group; and R is a C 1 -C 4 alkyl group, a C 2 -C 4 alkenyl group, a C 1 -C 4 haloalkyl group, a benzyl, phenethyl, chlorobenzyl or fluorobenzyl group, a C 3 - C 6 cycloalkyl group, a C 3 -C 6 cycloalkyl C 1 -C 4 alkyl group, a C 1 -C 4 alkoxy C 1 -C 4 alkyl group, a C 1 -C 4 hydroxyalkyl group, a C 1 -C 4 alkanoyloxy C 1 -C 4 alkyl group, a trihalomethyl C 1 -C 4 alkyl group, a C 1 -C 4 alkylthioalkyl group or a group of the formula ##STR8## (wherein n is an integer of 1 to 3; R 4 and R 5 are individually a C 1 -C 4 alkyl group provided that R 4 and R 5 may form together with the adjacent nitrogen atom an unsubstituted or optionally substituted 5-or 6-membered heterocyclic ring, which may further contain a hetero atom), which comprises contacting a 2-aminophenyl ketone derivative represented by the formula, ##STR9## wherein R 1 , R 2 and R 3 are as defined above, with an alkali metal hydride to form a metal salt of 2-aminophenyl ketone derivative represented by the formula, ##STR10## wherein R 1 , R 2 and R 3 are as defined above; and M is an alkali metal atom, thereafter reacting the resultant metal salt of the formula (III) with a compound of the formula RX where R is as defined above and X is halogen to prepare a 2-(N-mono-substituted amino) phenyl ketone derivative represented by the formula, ##STR11## wherein R 1 , R 2 , R 3 and R are as defined above, and then, reacting the compound of the formula (V) with a lower alkyl haloformate or a benzyl haloformate to yield a carbamate derivative represented by the formula, ##STR12## wherein R 1 , R 2 , R 3 and R are as defined above; and R 6 is a C 1 -C 4 alkyl group or a benzyl group, and finally reacting the compound of the formula (VI) with ammonia.