Efficient synthesis of 3-substituted indolizines via a [4+1] annulation reaction mediated by dimethyl-methoxymethylene-ammonium generated in situ

ORGN 683

Zhiqian Xia1, Shijie Zhang2, Teresa Przewloka2, Elena Kostik2, Dinesh Chimmanamada2, Shoujun Chen2, David James3, Hao Li2, Weiwen Ying2, Mitsunori Ono2, Keizo Koya2, and Lijun Sun2. (1) Chemistry, Synta Pharmaceuticals Corp, 45 Hartwell Ave., Lexington, MA 02421, (2) Synta Pharmaceuticals Corp, 45 Hartwell Avenue, Lexington, MA 02421, (3) DEPARTMENT OF CHEMISTRY, Synta Pharmaceuticals Corp, 45 Hartwell Avenue, Lexington, MA 02421
One of our drug discovery programs leads to the selection of a novel indolizine derivative (STA-5312) as a promising anticancer candidate for clinical development. The synthesis of STA-5312 requires an efficient method for the preparation of 3-acyl substituted indolizine. Herein we report the application of dimethyl-methoxymethylene-ammonium as a novel reagent for the facile synthesis of 3-acyl-indolizines (see reaction scheme). The process development of GMP-production of STA-5312 based on this key reaction will also be discussed.

 

New Reactions, Methodology, Heterocycles, Aromatics
8:00 PM-10:00 PM, Wednesday, August 25, 2004 Pennsylvania Convention Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 23, 2004 Pennsylvania Convention Center -- Hall D, Sci-Mix

Division of Organic Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004