Synthesis of Certain 6-Chloro 2-Substituted Quinazolin-4-Ones, 6-Chloro 2,4 Disubstituted Quinazolines and Related Fused Analogues as Counterparts of Folic Acid Analogues

Ali M. Abdelal

Department of Medicinal Chemistry, College of Pharmacy, University of Mansoura, Mansoura-355 16 Egypt

ABSTRACT:

The synthesis of a new series of 6-chloro 2-substituted quinazolin-4(3H)-one including variation in the 9-10 bridge region was conducted. Bromination of 6 -chloro-3-methylquinazolin -4 (3H)-one (!) with N-bromosuccinimide afforded the 2-broinomethyl derivative (2) Compound 1 was condensed with methylbenzoate in the presence of NaH (60%) to give 3. Compound 2 was converted to the 9,10-ethenyl precursor 5 through Wittig condensation with methyl 4-for-mylbenzoate. Saponification of compounds 4 and 5 in IN NaOH yielded the corresponding acids 6 and 7 respectively. Modification of compound 5 at the carbonyl group (C4) resulted in several quinazoline analogues. The 4,6-dichloro derivative 8 was allowed to react with different nucleophiles such as, aminoacetaldehybe dimethyl acetal, benzoic hydrazide and sodium azide to give compounds 9,10 and 11, respectively. Cyclizatton of compounds 9 and 10 afforded the corresponding tricyclic imidazo [1,2-c] quinazoline 12 and triazolo [4,3-c] quinazatine 13 derivatives respectively. Conversion of the azido derivative 11 the to the amino one 15 was also described.

KEYWORDS:

6-Chloro; Quinazolines; Analogues

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Copy the following to cite this article: Abdelal A. M. Synthesis of Certain 6-Chloro 2-Substituted Quinazolin-4-Ones, 6-Chloro 2,4 Disubstituted Quinazolines and Related Fused Analogues as Counterparts of Folic Acid Analogues. Orient J Chem 1992;8(4).

Copy the following to cite this URL: Abdelal A. M. Synthesis of Certain 6-Chloro 2-Substituted Quinazolin-4-Ones, 6-Chloro 2,4 Disubstituted Quinazolines and Related Fused Analogues as Counterparts of Folic Acid Analogues. Orient J Chem 1992;8(4). Available from: http://www.orientjchem.org/?p=39211