US 11,958,809 B2
Salt of omecamtiv mecarbil and process for preparing salt
Sheng Cui, Thousand Oaks, CA (US); Henry Morrison, Thousand Oaks, CA (US); Karthik Nagapudi, South San Francisco, CA (US); Shawn D. Walker, Woodland Hills, CA (US); Charles Bernard, Moorpark, CA (US); Karl Bennett Hansen, Cohasset, MA (US); Neil Fred Langille, Thousand Oaks, CA (US); Alan Martin Allgeier, Wilmington, DE (US); Steven M. Mennen, Thousand Oaks, CA (US); Jacqueline C. S. Woo, Sherwood Park (CA); Bradley Paul Morgan, Moraga, CA (US); and Alex Muci, San Francisco, CA (US)
Assigned to CYTOKINETICS, INC., South San Francisco, CA (US)
Filed by Cytokinetics, Inc., South San Francisco, CA (US)
Filed on Sep. 24, 2021, as Appl. No. 17/448,833.
Application 15/963,529 is a division of application No. 14/773,436, granted, now 9,988,354, issued on Jun. 5, 2018, previously published as PCT/US2014/027146, filed on Mar. 14, 2014.
Application 17/448,833 is a continuation of application No. 17/176,003, filed on Feb. 15, 2021, abandoned.
Application 17/176,003 is a continuation of application No. 16/920,155, filed on Jul. 2, 2020, abandoned.
Application 16/920,155 is a continuation of application No. 16/684,216, filed on Nov. 14, 2019, abandoned.
Application 16/684,216 is a continuation of application No. 15/963,529, filed on Apr. 26, 2018, abandoned.
Claims priority of provisional application 61/785,763, filed on Mar. 14, 2013.
Prior Publication US 2022/0153700 A1, May 19, 2022
Int. Cl. C07D 213/75 (2006.01); A61K 9/20 (2006.01); A61K 31/444 (2006.01); A61K 31/496 (2006.01); A61K 47/38 (2006.01); A61P 9/00 (2006.01); A61P 9/04 (2006.01); A61P 9/06 (2006.01)
CPC C07D 213/75 (2013.01) [A61K 9/2013 (2013.01); A61K 9/2018 (2013.01); A61K 9/2054 (2013.01); A61K 31/496 (2013.01); A61K 47/38 (2013.01)] 5 Claims
 
1. A method of preparing omecamtiv mecarbil dihydrochloride hydrate

OG Complex Work Unit Chemistry
comprising:
step (a) admixing methyl 4-(3-amino-2-fluorobenzyl)piperazine-1-carboxylate (Piperazine Aniline)

OG Complex Work Unit Chemistry
and phenyl (6-methylpyridin-3-yl)carbamate (Phenyl Carbamate·HCl)

OG Complex Work Unit Chemistry
in the presence of diisopropylethylamine and THF to form a solution of omecamtiv mecarbil free base;
step (b) swapping solvent of the solution of omecamtiv mecarbil free base to 2-propanol;
step (c) admixing the solution of omecamtiv mecarbil free base with hydrochloric acid in the presence of water to form omecamtiv mecarbil dihydrochloride hydrate.