Process development efforts toward a scalable synthesis of a next generation statin

ORGN 276

Michael M. Miller, michael.miller@bms.com, Lindsay Hobson, Kishta Katipally, Robert Livingston, Jan Spink, Kana Yamamoto, Otute Akiti, Subodh Deshmuk, Shannon Harper, Ehrlic Lo, Srinivas Tummala, John Young, and Rodney L. Parsons Jr. Departments of Chemical Process Research and Development & Drug Discovery Chemistry, Bristol-Myers Squibb Co, P.O. Box 5400, Princeton, NJ 08543-5400
An efficient and scalable process for the multi-kilogram preparation of a HMG CoA reductase inhibitor (1) will be presented. The development and implementation of a convergent and safe approach to the core pyrimidine scaffold was a key facet to the route selection. Specific highlights of the optimization efforts will be described, including the development of a dehydrogenation method for dihydropyrimidines, a thermochemically safe synthesis of the 1,2,4-aminotriazole fragment, and the incorporation of an “intermediate” salt drop to ensure API quality. Compound 1 was prepared in 10 linear steps in an overall 35% yield.

 

Biologically Active Molecules
8:00 AM-12:00 PM, Tuesday, April 8, 2008 Morial Convention Center -- Rm. R05, Oral

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008