Concise Synthesis of 2-Amino-4(3H)-quinazolinones from Simple (Hetero)aromatic Amines

Abstract

A novel and simple method of preparation of 2-alkylaminoquinazolin-4-ones with fused heteroaromatic rings from easily accessible (hetero)aromatic amines is described. The method is very efficient, and the 2-alkylaminoquinazolinone derivatives are obtained in three steps without chromatographic purification. The key step is the ring closure of the N-protected guanidine intermediates by intramolecular Friedel-Craft's type substitution.

Antiprotozoal activity and DNA binding of N-substituted N-phenylbenzamide and 1,3-diphenylurea bisguanidines

“…The first strategy using Lewis acids such as trimethylsilyl (TMSCl) chloride [21,22] and bromide (TMSBr) [20] to generate directly the guanidinium salts was mostly unsuccessful in our hands, leading to complex mixtures of partially and fully deprotected products together with 2-alkylamino(3H)quinazolin-4-one by-products as previously reported [22]. Apparently, the success of this deprotection protocol is very dependent on the R group present on the guanidine moiety [e.g.…”

Catalyst-free synthesis of quinazolin-4-ones from (hetero)aryl-guanidines: application to the synthesis of pyrazolo[4,3-f]quinazolin-9-ones, a new family of DYRK1A inhibitors

“…Most of them involve the pyrimidine ring closure and require orthosubstituted benzenes, such as anthranilic acids, as starting materials. We and others groups recently reported short and efficient pathways using simple aromatic or heteroaromatic amines as precursors for the synthesis of quinazoline [10][11][12] or quinazolin-4-one derivatives [13,14].…”

“…So far, quinazolin-4-one syntheses required the use of Lewis acid catalysts [13] or toxic reagents [14]. Considering the importance of this class of molecules, finding greener alternatives to these procedures appeared highly desirable.…”

Efficient Room‐Temperature One‐Pot Synthesis of 2‐Amino‐3‐alkyl(3‐aryl)quinazolin‐4(3H)‐ones

“…More recently, several new routes have been reported, including the copper-catalyzed amination of 2-halobenzoic acids, [20] bethoxy-protected arylguanidines, [21] the base-promoted intramolecular ring closure of ortho-fluorobenzoylguanidines, [22] and tandem amination/palladium-catalyzed cyclocarbonylation from carbodiimide derivatives. [23] Although these methods offer multiple entries to the synthesis of 2-aminoquinazolin-4(3H)-ones, most of them are limited regarding the synthesis of 2-amino-3-substitutedquinazolin-4(3H)-ones.…”