Synthesis of some substituted furo[3,2-g]chromeno[2,3-c]pyrazole and pyrazoline derivatives from 5-hydroxybergapten and 5-hydroxyisopimpinellin as EGFR and VEGFR-2 kinase inhibitors

A series of substituted 7H-furo[3,2-g]chromen-7-one and furo[3,2-g]chromeno[2,3-c]pyrazole derivatives ( 2–9 ) were synthesized by using 5-hydroxy-4-methoxy-7 H -furo[3,2- g ]chromen-7-one (5-hydroxybergapten) and 5-hydroxy-4,9-dimethoxy-7 H -furo[3,2- g ]chromen-7-one (5-hydroxyisopimpinellin) ( 1 ) as starting materials. Compound 1 reacted with amino acid esters to give the corresponding 5 - N -amino acid derivatives 2 and 3 , respectively. Bromination of 1 gave the corresponding 6 -bromo analouges 4 , that were treated with amino acids esters to give the corresponding 6 - N -amino acids analogues 5 . Treatment of the later with hydrazine hydrate led to cleavage of the pyran ring and gave the corresponding pyrazoline benzofuran derivatives 6 . Formylation of 1 gave aldehyde derivative 7 , which was condensed with amino acid to give the corresponding 5 - N -amino-6-formyl derivatives 8 . Cyclization of compounds 8 with hydrazine hydrate gave the corresponding pyrazoline derivatives 9 . All synthesized compounds were tested as EGFR and VEGFR-2 kinase inhibitors.