Here we report a multicomponent domino reaction for the synthesis of a combinatorial library of spiro-oxindole derivatives with a pyrido[2,3-d]pyrimidine moiety by a one pot, eco-efficient three component reaction involving isatin, 6-aminouracil and acetyl acetone which is catalyzed by an organocatalyst in water as the reaction medium. A heterocyclic molecule which contains a highly functionalized bioactive spiro-oxindole and a pyrido[2,3-d]pyrimidine ring in one nucleus is very important due to its bioactive nature. This method avoids the use of costly and toxic catalysts and organic solvents which show a number of side effects on the environment and human beings. The simplicity and versatility of this eco-efficient method is described.