Novel and regioselective synthesis of N3-[(4-aminosulfonyl)phenyl]-1-(2’, 6’-difluorobenzoyl)-1H-1, 2,4-triazole-3, 5-diamine: A selective kinase inhibitor

ORGN 620

Tong Xiao1, Jef Adriaensen2, Shichei Andega3, Rick Bruce3, Sergio Cesco-Cancian4, Dirk Cleeren2, Annelies Decorte2, Jules Dickens2, Richard Dunphy5, Anthony Ginnetti4, Koen Heymans2, Aihua Huang5, Jessica Mayer4, David C. Palmer4, Keith Sampino5, Brigitte E. Segmuller5, Charles Shaw5, Kirk Sorgi, ksorgi@prdus.jnj.com6, Sigrid Stokbroekx2, Stephen Stefanick7, Justin Weaver3, Robin R. H. Webster4, and Dawei Xu5. (1) Global Chem Pharm, Chemical Development, Johnson & Johnson Pharmaceutical Research & Development, 1000 US 202 Highway, Box 300, Raritan, NJ 08869, (2) Johnson & Johnson Pharmaceutical Research &Development, L.L.C, Turnhoutseweg 30, Beerse, 2340, Belgium, (3) Johnson & Johnson Pharmaceutical Research& Development, L.L.C, Welsh & Mckean Roads, Spring House, PA, (4) Chemical Development, Johnson & Johnson Pharmaceutical Research & Development, L.L.C, 1000 US 202 Highway, Raritan, NJ 08869, (5) Analytical development, Johnson & Johnson Pharmaceutical Research & Development, L.L.C, 1000 US 202 Highway, Raritan, NJ 08869, (6) Chemical Development, Johnson & Johnson Pharmaceutical Research & Development, 1000 US 202 Highway, Box 300, Raritan, NJ 08869, (7) Global Chem Pharm, Chemical Development, Johnson & Johnson Pharmaceutical Research & Development, L.L.C, 1000 US 202 Highway, Raritan, NJ 08869
N3-[(4-aminosulfonyl)phenyl]-1-(2',6'-difluorobenzoyl)-1H-1,2,4-triazole-3,5-diamine is a selective cyclin dependent kinase inhibitor that shows promise as an anti-tumor agent. It was regioselectively synthesized in high yield from diphenylcyanocarbonimidate (DPCCI), 4-aminobenzenesulfonamide and 2,6-difluorobenzoyl hydrazide. The reaction sequence can be conducted in one-pot with no isolated intermediates. A process to generate the most stable polymorph was also developed. The methodology has been extended to prepare regioselectively a wide variety of 1-acyl-3,5-diamino-1,2,4-triazoles.
 

Asymmetric Reactions, Heterocycles, Aromatics, Combinatorial, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 31 August 2005 Washington DC Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005