US 12,269,811 B2
Synthesis of omecamtiv mecarbil
Sebastien Caille, Thousand Oaks, CA (US); Kyle Quasdorf, Thousand Oaks, CA (US); Philipp C. Roosen, Thousand Oaks, CA (US); Xianqing Shi, Newbury Park, CA (US); Andrew Cosbie, Ventura, CA (US); Fang Wang, Simi Valley, CA (US); Zufan Wu, Walnut, CA (US); Archana Neergunda, Simi Valley, CA (US); Bin Peter Quan, Thousand Oaks, CA (US); and Lianxiu Guan, Camarillo, CA (US)
Assigned to Amgen Inc., Thousand Oaks, CA (US)
Filed by Amgen Inc., Thousand Oaks, CA (US)
Filed on Jul. 26, 2023, as Appl. No. 18/359,467.
Application 18/359,467 is a division of application No. 17/324,867, filed on May 19, 2021, granted, now 11,753,394.
Application 17/324,867 is a division of application No. 16/607,940, granted, now 11,040,956, issued on Jun. 22, 2021, previously published as PCT/US2018/040176, filed on Jun. 29, 2018.
Claims priority of provisional application 62/664,363, filed on Apr. 30, 2018.
Claims priority of provisional application 62/527,174, filed on Jun. 30, 2017.
Prior Publication US 2023/0373955 A1, Nov. 23, 2023
Int. Cl. C07D 295/205 (2006.01); C07D 213/75 (2006.01); C07D 241/04 (2006.01); C07D 401/12 (2006.01)
CPC C07D 401/12 (2013.01) [C07D 241/04 (2013.01)] 13 Claims
 
1. A process for preparing omecamtiv mecarbil dihydrochloride hydrate comprising
(a) admixing methyl 4-(3-amino-2-fluorobenzyl) piperazine-1-carboxylate

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 phenyl (6-methylpyridin-3-yl) carbamate

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 and a trialkylamine in acetonitrile and tetrahydrofuran to form a solution of crude omecamtiv mecarbil;
(b) isolating omecamtiv mecarbil free base from the solution of crude omecamtiv mecarbil; and
(c) admixing the isolated omecamtiv mecarbil free base with 2 to 3 molar equivalents of hydrochloric acid in isopropanol and water to form omecamtiv mecarbil dihydrochloride hydrate

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