5-Fluoro-2-(4-(methylsulfonyl)-phenyl)pyridine
1H NMR (400 MHz, DMSO-d6) δ 8.73 (d, J = 2.8 Hz, 1H), 8.31 (bd, J = 8.8 Hz, 2H), 8.20 (dd, J = 8.8, 4.3 Hz, 1H), 8.04 (bd, J = 8.5 Hz, 2H), 7.91 (td, J = 8.8, 3.0 Hz, 1H), 3.27 (s, 3H).
13C (100.6 MHz, DMSO-d6) 158.3, 151.3, 142.7, 141.3, 138.4, 128.0, 127.8, 125.0, 124.8, 123.3, 123.2, 44.0.
HRMS calcd for C12H11FNO2S (M + H)+ 252.0489, found, 252.0485.
Paper
Development of Large-Scale Routes to Potent GPR119 Receptor Agonists
Richard T. Matsuoka*†, Eric E. Boros#, Andrew D. Brown†, Kae M. Bullock†, Will L. Canoy‡, Andrew J. Carpenter#, Jeremy D. Cobb†,Shannon E. Condon†, Nicole M. Deschamps†, Vassil I. Elitzin†, Greg Erickson†,Jing M. Fang#, David H. Igo§, Biren K. Joshi‡, Istvan W. Kaldor#, Mark B. Mitchell†, Gregory E. Peckham#, Daniel W. Reynolds‡, Matthew C. Salmon†, Matthew J. Sharp†, Elie A. Tabet#, Jennifer F. Toczko†, Lianming Michael Wu‡, and Xiao-ming M. Zhou†
†API Chemistry Department, ‡Analytical Science & Development Department, #Medicinal Chemistry Department, and§Particle Sciences and Engineering Department, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, Pennsylvania 19406, United States
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00157, http://pubs.acs.org/doi/abs/10.1021/acs.oprd.6b00157
Publication Date (Web): July 13, 2016
Copyright © 2016 American Chemical Society
*E-mail: richard.t.matsuoka@gsk.com.
Abstract
Practical and scalable syntheses were developed that were used to prepare multikilogram batches of GSK1292263A (1) and GSK2041706A (15), two potent G protein-coupled receptor 119 (GPR119) agonists. Both syntheses employed relatively cheap and readily available starting materials, and both took advantage of an SNAr synthetic strategy.
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