Amide formation isatoic anhydride

A more highly oxidized derivative of quinazoline forms the heterocyclic moiety of a compound with CNS activity. Condensation of the aminopropylpiperazine 141 with isatoic anhydride gives the anthranilamide 142. Reaction of that amide with phosgene gives directly the heterocyclic ring. (The reaction may proceed by initial formation of the carbamoyl chloride ... 

Isatoic anhydride itself (91-1), when allowed to react with the primary amine (91-2), gives the corresponding amide (91-3), again with the expulsion of carbon dioxide. Treatment of the intermediate with phosgene results in the formation of a quinazolodione ring. There is thus obtained the serotonin blocking compound doperidone (91-4) [101], which is described as a sedative. 

Isatoic anhydrides 11 are transformed with ammonia into quinazoline-2,4(li/,3i/)-diones 12 with concomitant formation of the corresponding anthranilic acids -or anthranil-amides. The reaction lacks generality and has seldom been used for the synthesis of quin-azoline-2.4(177,37f)-diones. 

The construction of six-membered rings with three nitrogen atoms on the basis of isatoic anhydrides has only been described for 1,2,3-benzotriazines. This method for the synthesis of the latter includes reaction of the anhydrides with primary amines and subsequent diazotization of the obtained amino amides, which dictates the use of initial isatoic anhydrides not containing substituents at the nitrogen atom. Thus, the action of sodium nitrite and hydrochloric acid on the amino amides 161, formed from the anhydrides 1, 10, 162 and imidazolylalkylamines, leads to diazotization and cyclization with the formation of derivatives 208 of benzo-l,2,3-triazin-4-ones (yields 36-85%) [96, 126],... 

An interesting modification of Camps reaction was presented recently. It was based on the use of isatoic anhydride or benzoxazinones as active components for the in situ formation of intermediate amides, which were readily cyclized to the desired products. Thus, reaction of isatoic anhydride or benzoxazinones with malonates and/or ketoesters afforded libraries of quinoline compounds in high yields even at multikilogram scale. ... 

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