An efficient and practical synthesis of a novel human growth hormone secretagogue receptor

ORGN 426

Zhongmin Xu, zhongmin.xu@bms.com, Jollie D. Godfrey, Mark D. Schwinden, Akin H. Davulcu, Rita Fox, Bharat P. Patel, Wendel W. Doubleday, and Rodney L. Parsons Jr. Process Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, NJ 08543
An efficient synthesis was developed for the large scale preparation of the Growth Hormone Secretagogue candidate 1a. An important feature of this synthesis is the preparation of the substituted tetrazole 3 via a highly sensitive oxazoline intermediate 2. This synthesis also highlights an efficient preparation of key isocyanate intermediate 4 and its one-pot coupling with tetrazole 3 to produce the target compound. Evaluation of the phosphate salt 1b, which imparts enhanced stability is also discussed.

 

Process R&D and Practical Syntheses of Medicinal Agents
1:00 PM-4:40 PM, Tuesday, 12 September 2006 Moscone Center -- Room 132, Oral

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006