Pilot-Plant Preparation of an αvβ3 Integrin Antagonist. Part 2. Synthesis of N-[2-(5-Hydroxy-4,6-tetrahydropyrimidine)]-3-amino-5-hydroxybenzoic Acid

Studies directed toward the process research and development of a scalable method for preparing tetrahydropyrimidine 2, a key intermediate to the αvβ3 integrin antagonist 1, are described. A linear approach employing 3-amino-5-hydroxybenzoic acid, methyl isothiocyanate, and 1,3-diaminopropan-2-ol as key reagents is detailed. The results of process development research, a successful pilot run, and a production campaign are explained.