Efficient Niementowski synthesis of novel 1,3,10,12-tetra-substituted-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-ones

Abstract

Novel 1,3,10,3':4,5]pyrimido [6,1-b]quinazolin-8-ones were synthesised by a Niementowski reaction involving condensation of substituted anthranilic acids with a 5,7-disubstituted-3H-pyrido[2,3-d]pyrimidin-4-ones. Microwave irradiation in polyphosphoric acid media was used in order to improve reactions where classical or direct fusion method was limited. The synthesis of title compounds highlights a comparative study of the classical, microwave technique and direct fusion methods.

Advances in the chemical and biological diversity of heterocyclic systems incorporating pyrimido[1,6-a]pyrimidine and pyrimido[1,6-c]pyrimidine scaffolds

“…The products 119a–u were formed through initial condensation between the amino group of the anthranilic acid and the carbonyl group of the pyrimidine ring and a subsequent intramolecular cyclocondensation step of the generated intermediate A-5 ( Scheme 28 ). 92 …”

“…A simple multi-step synthetic method was reported by Abdel-Hafez et al 88 The reaction of enaminonitriles of thiophenes 111a-e with formic acid at reux temperature yielded thienopyrimidinones 112a-e, respectively. 90 Further treatment of 112a-e with phosphorus oxychloride under microwave irradiation conditions yielded the anticipated chlorinated thienopyrimidines 113a-e. A series of 7H-thienopyrimidoquinazolinones 115a-o was synthesized by Niementowski reactions 91 of 3a-e with anthranilic acids 114a-c under microwave irradiation or reux [92][93][94][95] conditions. The products 115a-o were formed through nucleophilic attack of the amino group of the anthranilic acids at C4 of thieno [2,3-d] pyrimidines 113a-e, followed by 1,3 proton transfer and subsequent intramolecular cyclocondensation (Scheme 27).…”

“…The products 119a-u were formed through initial condensation between the amino group of the anthranilic acid and the carbonyl group of the pyrimidine ring and a subsequent intramolecular cyclocondensation step of the generated intermediate A-5 (Scheme 28). 92 Treatment of Visnagen 120a (R ¼ H) and Khellin 120b (R ¼ OCH 3 ), respectively, in an aqueous solution of potassium hydroxide generated the respective 5-acetyl-6-hydroxy-4methoxybenzofuran derivatives 121a and 121b, which were condensed with dihydropyrimidinone 24 in DMF at reux temperature to yield 3H-furopyrimidoquinazolinones 123a and 123b. The reactions of benzofuran derivatives 121a and 121b with dihydropyrimidinone 24 produced compounds 122a and 122b aer a short time; these were condensed in DMF to afford the target compounds 123a and 123b, respectively.…”

“…Two series of thienopyrimidoquinazolinones 115a-o and pyridopyrimidoquinazolinones 119a-u (Schemes 27 and 28 and Fig. 3) 92,96 were assessed as anticonvulsant agents (anti-MES and anti-scPTZ). The compounds showed potent activities.…”

Survey of Recent Literature Related to the Biologically Active 4(3H)-Quinazolinones Containing Fused Heterocycles

“…As an example, microwave-assisted methodologies were used for the synthesis of triazabenzo[a]indeno[1,2-c]anthracen-5-ones 67 [90], and pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-ones 69 (Fig. 24) [91].…”