A cyclative cleavage approach to solid-phase synthesis of annulated pyrimidinones using Baylis–Hillman derivatives

Abstract

An efficient and robust solid-phase synthesis of 6-substituted-2,5,6,8-tetrahydro-3 H-imidazo[1,2- a]pyrimidin-7-ones, 3-substituted-1,3,4,6,7,8-hexahydro-pyrimido[1,2- a]pyrimidin-2-ones and 3-substituted-3,4,6,7,8,9-hexahydro-1 H-pyrimido[1,2- a][1,3] diazepin-2-ones from the acetates of Baylis–Hillman adducts employing Michael addition of diamines followed by intramolecular cyclization with cyanogen bromide and, finally, base promoted cyclative cleavage has been developed. The procedure is validated through an automated parallel synthesis of a small library of fourteen compounds of the 3 H-imidazo[1,2- a]pyrimidin-7-one series.