Synthesis of 3-amino-4(3H)-quinazolinones from N-(2-carbomethoxyphenyl)imidate esters

Abstract

Novel difunctional aromatic synthons consisting of iV-(2-carbomethoxyphenyl) imidate esters were synthesized by treatment of methyl anthranilate esters with aliphatic ortho esters. Treatment of the imidates with hydrazine, methylhydrazine, and phenylhydrazine yielded only quinazolinones and not isomeric l,3,4-benzotriazepin-5-ones.The type of products obtained gave information relevant to elucidation of the mechanism of cyclization and the relative reactivities of the ester and imidate groups.

Microwave-Assisted Synthesis of Quinazolines and Quinazolinones: An Overview

“…As a result, the reaction with ortho-esters required a catalytic amount of PTSA. The reaction occurred within a much reduced time under MWI with respect to the conventional heating procedure (Leiby, 1985). A modification of the above method, which is environmentally friendly, involved the synthesis of fluorine-containing 4(3H)quinazolinones 160 using fluorinated anilines 159 in the absence of a solvent and catalysts (Scheme 65) (Wenli et al, 2011).…”

“…As a result, the reaction with ortho-esters required a catalytic amount of PTSA. The reaction occurred within a much reduced time under MWI with respect to the conventional heating procedure (Leiby, 1985 ).…”

Oxygen analogues of the benzodiazepine alkaloids sclerotigenin and circumdatin F

“…The low yield might be due to hydrolysis of the starting material 11, but the cyclised adduct 13 [16] could also be isolated as a coproduct in 5% yield. Optimisation assays towards direct cyclisation from 11 to the quinazolin-4-one 13 gave no satisfactory results in our hands.…”

“…Instead was compound 12 then heated at reflux in DMF for 65 hours and the quinazolinone adduct 13 was isolated in 39% yield. The total yield was only 4.7% yield in two steps, but prior synthesis of compound 13 has been obtained by allowing the appropriate imidate ester to stand for 15 months [16]. Introduction of an α-bromine atom in 2-ethylquinazolinone using bromine and NaOAc in acetic acid is known [17].…”

“…The benzoxazinone 11 [15], was heated at reflux with methyl anthranilate in acetic acid for 3 hours and compound 12 could be isolated in 12% yield (Scheme 3). The low yield might be due to hydrolysis of the starting material 11, but the cyclised adduct 13 [16] could also be isolated as a coproduct in 5% yield. Optimisation assays towards direct cyclisation from 11 to the quinazolin-4-one 13 gave no satisfactory results in our hands.…”