An Efficient Synthesis of Spiro-oxindole Derivatives by Three-Component Reactions in Water

An efficient synthesis of (3S)-1,1',2,2',3',4',6',7'-octahydro-9'-nitro-2,6'-dioxospiro[3H-indole-3,8'-[8H] pyrido[1,2-a]pyrimidine]-7'-carbonitrile is achieved via a three-component reaction of isatin, ethyl cyanoacetate, and 1,2,3,4,5,6-hexahydro-2-(nitromethylidene)pyrimidine. The present method does not involve any hazardous organic solvents or catalysts. Also the synthesis of ethyl 6'-amino-1,1',2,2',3',4'-hexahydro-9'-nitro-2-oxospiro[3H-indole-3,8'-[8H] pyrido[1,2-a]pyrimidine]-7'-carboxylates in high yields, at reflux, using a catalytic amount of piperidine, is described. The structures were confirmed spectroscopically (IR, H-1- and C-13-NMR, and EI-MS data) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).