Methodology for the Preparation of 2-Argininylbenzothiazole

• Published in: Journal of organic chemistry Vol. 72; no. 25; pp. 9798 - 9801
• Main Authors: Kenney, Birdella D, Breslav, Michael, Chang, Rosie, Glaser, Roland, Harris, Bruce D, Maryanoff, Cynthia A, Mills, John, Roessler, Armin, Segmuller, Brigitte, Villani, Frank J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.12.2007; Amer Chemical Soc
• Subjects: Arginine - analogs & derivatives; Arginine - chemical synthesis; Arginine - chemistry; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; Chemistry; Chemistry, Organic; Crystallization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Imidazoles - chemistry; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Time Factors; BENZOTHIAZOLE; POTENT; INHIBITORS; CRYSTAL-STRUCTURE; Imidazole derivatives; Sulfur nitrogen heterocycle; Stability; Nitrogen heterocycle; Thiazole derivatives; Enzyme inhibitor; Benzothiazole derivatives; Optimization; Ester; α-Aminoacid; Grignard reagent; Arginine; Aminoacid; Chemical synthesis; Nucleophile
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo7019543

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.