Methodology for the Preparation of 2-Argininylbenzothiazole

An efficient process to produce kilogram quantities of a key
argininylbenzo[d]thiazole intermediate was developed for the
preparation of the tryptase inhibitor RWJ-56423. A variety
of activated arginine esters and benzo[d]thiazole nucleophiles
were evaluated as coupling partners. Our work led to the
selection and optimization of an argininyl imidazolide ester
and benzothiazol-2-yl MgCl nucleophile. This paper focuses
on the preparation, use, and stability of the benzothiazol-2-yl Grignard reagents.