1029317-21-2Relevant academic research and scientific papers
Development of the Commercial Route for the Manufacture of a 5-Lipoxygenase Inhibitor PF-04191834
Chekal, Brian,Damon, David,Lafrance, Danny,Leeman, Kyle,Mojica, Carlos,Palm, Andrew,St. Pierre, Michael,Sieser, Janice,Sutherland, Karen,Vaidyanathan, Rajappa,Van Alsten, John,Vanderplas, Brian,Wager, Carrie,Weisenburger, Gerald,Withbroe, Gregory,Yu, Shu
, p. 1944 - 1953 (2015)
A de novo three-step-one-pot process for the formation of PF-04191834 was developed. This methodology employed inexpensive, odorless, and readily available commodity chemical iso-octyl-3-mercaptopropionate as a sulfur source, which could be a general alternative to the popular TIPS-SH in the formation of diarylthioethers via Migita coupling. A kinetic study revealed that, at high temperature, reductive elimination could be the rate-limiting step in the catalytic cycle, which opens pathways for the generation of undesired impurities. By proper control of the reaction conditions, the desired API was synthesized in >70% crude yield and in 55% isolated yield after vigorous purifications. This process was successfully demonstrated on a 20 kg scale.
Development an efficient route to the 5-lipoxygenase inhibitor PF-04191834
De Koning, Pieter D.,Murtagh, Lorraine,Lawson, Jon P.,Vonder Embse, Richard A.,Kunda, Sastry A.,Kong, Wei
experimental part, p. 1046 - 1051 (2012/01/04)
A convergent six-step process for the synthesis of PF-04191834 (1), a potent and selective 5-lipoxygenase inhibitor, has been developed and used to deliver over 20 kg of API. The process uses the same bond-forming steps as the initial medicinal chemistry
Pyrazole Analogs
-
Page/Page column 14; 16-17, (2008/12/05)
The invention relates to the compounds of formula (I): or a pharmaceutically acceptable salt and solvate thereof, wherein R1 is F or H and to processes for the preparation of, intermediates used in the preparation of, compositions containing th
