A novel three-component synthesis of tetrahydrofuro[2,3-c]pyridines I (R1 = PhCH2; R2 = EtO2C; R3 = Me2CH, n-hexyl, PhCH2CH2, 4-O2NC6H4, etc.; R4R5N = morpholino, piperidino, pyrrolidino, diethylamino) from readily accessible starting materials is described. Simply heating a toluene soln. of an aminopentynoate R1NH(CH2)2C==CR2, an aldehyde R3CHO, and an alpha -isocyanoacetamide R4CH(NC)CONR5R6 (R4 = H, PhCH2) in the presence of ammonium chloride provided I in good to excellent yields. The fused ring system is produced in this one-pot process by the concomitant formation of five chem. bonds. [on SciFinder (R)]