US 11,674,163 B2
Processes for the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof
Antonio Garrido Montalban, San Diego, CA (US); Daniel J. Buzard, San Diego, CA (US); John A. DeMattei, Berthoud, CO (US); Tawfik Gharbaoui, Escondido, CA (US); Stephen R. Johannsen, San Diego, CA (US); Ashwin M. Krishnan, San Diego, CA (US); Young Mi Kuhlman, Plainsboro, NJ (US); You-An Ma, Poway, CA (US); Michael John Martinelli, San Diego, CA (US); Suzanne Michiko Sato, San Diego, CA (US); and Dipanjan Sengupta, San Diego, CA (US)
Assigned to Arena Pharmaceuticals, Inc., New York, NY (US)
Filed by Arena Pharmaceuticals, Inc., San Diego, CA (US)
Filed on Sep. 14, 2021, as Appl. No. 17/474,777.
Application 14/464,251 is a division of application No. 13/575,458, granted, now 8,853,419, issued on Oct. 7, 2014, previously published as PCT/US2011/000153, filed on Jan. 27, 2011.
Application 17/474,777 is a continuation of application No. 15/238,014, filed on Aug. 16, 2016, granted, now 11,149,292.
Application 15/238,014 is a continuation of application No. 14/870,752, filed on Sep. 30, 2015, granted, now 9,447,041, issued on Sep. 20, 2016.
Application 14/870,752 is a continuation of application No. 14/464,251, filed on Aug. 20, 2014, granted, now 9,175,320, issued on Nov. 3, 2015.
Claims priority of provisional application 61/336,835, filed on Jan. 27, 2010.
Prior Publication US 2022/0259627 A1, Aug. 18, 2022
Int. Cl. C12P 17/10 (2006.01); C07D 209/80 (2006.01); C07D 209/94 (2006.01); C07C 17/278 (2006.01); C07D 209/88 (2006.01); C07D 295/155 (2006.01)
CPC C12P 17/10 (2013.01) [C07C 17/278 (2013.01); C07D 209/80 (2013.01); C07D 209/88 (2013.01); C07D 209/94 (2013.01); C07D 295/155 (2013.01); C07B 2200/13 (2013.01)] 15 Claims
 
1. A process for preparing an L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid of Formula (Ia):

OG Complex Work Unit Chemistry
comprising the following steps:
a) hydrolyzing a compound of Formula (IIk):

OG Complex Work Unit Chemistry
wherein R3 is C1-C6 alkyl;
in the presence of a lipase and a hydrolyzing-step solvent to form said (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid of Formula (Ia); and
b) contacting said (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid (Formula (Ia)) with L-arginine or a salt thereof, in the presence of a contacting-step solvent and H2O to form said L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid of Formula (Ia),
wherein the molar ratio between (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid (Formula (Ia)) and L-arginine is about 1.0: 1.0 to about 1.0: 1.2,
and wherein the contacting in step b) further comprises the step of adding an aqueous solution of L-arginine to a first contacting mixture comprising (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid (Formula (Ia)) and the C1-C6 alcohol to form a second contacting mixture,
wherein the first contacting mixture is at a temperature of about 45° C. to about 75° C.