The Development of Practical Synthetic Routes to a CB2 Agonist: Efficient Construction of a Densely Substituted Purine Core

Abstract

An efficient and scalable process for the preparation of a purine-based CB2 agonist was developed. The production route to the requisite purine core relies on N-acylation and sequential substitution of a 5-amino-4,6-dichloropyrimidine with two amine building blocks followed by a cyclocondensation reaction. The chemistry was successfully employed to rapidly prepare over 5 kg of the active pharmaceutical ingredient. To further improve efficiencies, postproduction development resulted in a rearranged synthesis which reduced the need for pressure reactors and introduced the most costly reagent in the final step.