Direct Amination and Synthesis of Fused N-Substituted Isothiochromene Derivatives

Isothiochromene[3,4-d] pyrimidine derivatives 2, 3, and 4a,b were synthesized from the reaction of 3-amino-1-(pyridin-4-yl)-5-(pyridin-4-ylmethylene)-5,6,7,8-tetrahydro-1H-isothiochromene-4-carbonitrile 1 with acetic anhydride, formamide, urea, or thiourea in appropriate experimental conditions. Combination of 1 with carbon acid derivatives afforded isothiochromene [3,4-b]pyridine 6-8 in good yield. A simple approach for N-substituted fused isothiochromene derivatives has been explored. A POCl3-mediated direct amination of isothiochromene amide 2 with NH2-heterocycles, secondary amines, and carbohydrazides is described and compared with classical method, yielding 10-14. The structures of the newly synthesized compounds were elucidated on the basis of elemental analysis, and spectral data.