Synthesis, characterization and biological evaluation of the novel chromenopyridothiazolopyrimidines and chromenopyridopyrimidothiazolo-pyrimidines

• Published in: Synthetic communications 2023-02, Vol.53 (4), p.332-344
• Main Authors: Alshaye, Najla A., Ibrahim, Magdy A.
• Format: Article
• Language: English
• Subjects: Acetyl chloride; Annulated coumarin; Anticancer properties; Antiinfectives and antibacterials; Carbon disulfide; Chloroacetic acid; chromenopyridothiazolopyrimidines; electrophilic reagents; heterocyclization; Nucleophiles; Pyrimidines; Reagents; Synthesis; Thiobarbituric acid
• ISSN: 0039-7911; 1532-2432
• DOI: 10.1080/00397911.2023.2172684

Friedländer reaction of 4-aminocoumarin-3-carboxaldehyde (1) with thiobarbituric acid provided 2-thioxochromenopyridopyrimidine 2 which employed as a synthetic intermediate to create a novel annulated chromenopyridothiazolopyrimidines. Treatment of compound 2 with a diversity of nucleophiles including; dibromoethane, oxalyl chloride, phenacyl bromide, chloroacetic acid, 3-chloropentanedione, ethyl 2-chloro-3-oxobutanoate, chloroacetonitrile and bromomalononitrile afforded chromenopyridothiazolopyrimidines 3-10, respectively. Acidic hydrolysis of carbonitrile 10 afforded the corresponding carboxamide derivative 11. Compound 11 reacted with some mono-electrophilic reagents namely acetyl chloride, benzoyl chloride, chloroacetyl chloride, triethyl orthoformate, diethyl carbonate, and carbon disulfide producing the first known chromeno[3′,4′:5,6]pyrido[2,3-d]pyrimido [4',5':4,5][1,3]thiazolo[3,2-a]pyrimidines 12-17. The antimicrobial and anticancer activities were estimated for the synthesized products and some of them appeared notable activities. The structural elucidation of the newly synthesized products was determined using analytical and spectroscopic data.