Synthesis of Thiazolo[5,4-d]pyrimidine, Thiazolo[5,4-b]pyridine, Thiazolo[4,5-b]pyrrolizine and Thiazolo[5,4-d]thiazaphosphinine

Abstract

5-amino-2-methylsulfanyl-thiazole-4-carboxylic acid ethyl ester 1 reacted with malononitrile, benzoylisothiocyanate, and 2-(methylsulfanyl-phenylaminomethylene)malononitrile to furnish the thiazolopyrimidine-2-one derivatives 2–4, respectively. 1 reacted with the dipotassium salt of the 2-dimercaptomethylene-malononitrile prepared by the reaction of malononitrile and CS 2 and KOH in the presence of TBAB under solid–liquid phase transfer catalysis to give 5. Reacting 1 with triethyl orthoformate, chloroacetyl chloride, and 2,5 dimethoxy tetrahydrofuran afforded 6–8. The reaction of 1 with Lawesson's reagent gave 9. The reaction of 1 with benzylidinemalononitrile gave 10. The reaction of hydrazine hydrate with 1 and/or 6 afforded 11 and 12, respectively. 7 reacted with malononitrile to give 13. The cyclization of 8 by the action of PPA gave 14. Thiazole-4-carbohydrazide 11 reacted with acetic anhydride/acetic acid mixture and with formic acid to yield 15 and 16, respectively. 11 reacted with p-chloro benzaldehyde to give 17. The treatment of compound 17 and/or 11 with triethyl orthoformate afforded 18 and 19, respectively. The reaction of 11 with CS2 and with 2-(bismethylsulfanyl-methylene)malononitrile gave 20 and 21, respectively.