Preparation of Guanine PDE Inhibitors:  Development of the Common Synthetic Route Strategy. A Case Study

A single synthetic route, called the chloropurine route, capable of quickly delivering initial kilogram quantities of several chiral as well as achiral guanine phosphodiesterase inhibitors of increasing complexity is described. During the course of this work, unraveling the formation mechanism of chloropurines allowed for the scale-up of the key intermediates. The mechanism for the cyclization of the chiral five-membered amino alcohols and its implication on the enantiomeric purity needed for this step are also described.