US 12,221,413 B2
Processes to produce brivaracetam
Peng Wang, Scotch Plains, NJ (US); Pixu Li, Suzhou (CN); Qiang Wei, Suzhou (CN); and Yuanhua Liu, Suzhou (CN)
Assigned to SUZHOU PENGXU PHARMATECH CO. LTD., Suzhou Jiangsu (CN)
Filed by SUZHOU PENGXU PHARMATECH CO. LTD., Suzhou Jiangsu (CN)
Filed on Jan. 24, 2019, as Appl. No. 16/256,522.
Application 16/256,522 is a division of application No. 15/575,373, granted, now 10,221,134, previously published as PCT/US2016/033965, filed on May 24, 2016.
Claims priority of application No. 201510271449.6 (CN), filed on May 25, 2015; application No. 201510430387.9 (CN), filed on Jul. 21, 2015; application No. 201510648574.4 (CN), filed on Oct. 10, 2015; and application No. 201610099672.1 (CN), filed on Feb. 24, 2016.
Prior Publication US 2019/0152908 A1, May 23, 2019
Prior Publication US 2024/0199541 A9, Jun. 20, 2024
Int. Cl. C07D 207/27 (2006.01); A61K 31/4015 (2006.01); C07C 53/19 (2006.01); C07C 53/50 (2006.01); C07C 67/307 (2006.01); C07C 69/63 (2006.01); C07C 71/00 (2006.01); C07C 209/08 (2006.01); C07C 231/14 (2006.01); C07C 233/05 (2006.01); C07C 237/06 (2006.01)
CPC C07D 207/27 (2013.01) [A61K 31/4015 (2013.01); C07C 53/19 (2013.01); C07C 53/50 (2013.01); C07C 67/307 (2013.01); C07C 69/63 (2013.01); C07C 71/00 (2013.01); C07C 209/08 (2013.01); C07C 231/14 (2013.01); C07C 233/05 (2013.01); C07C 237/06 (2013.01)] 9 Claims
 
1. A process for stereoselective preparation of brivaracetam XII comprising converting a compound of formula VII to brivaracetam XII:

OG Complex Work Unit Chemistry
wherein R1 is H, saturated or unsaturated C1-20 alkyl or C1alkyl-unsubstituted or substituted aryl;
and X is Cl, Br, I, OMs, or OTs; and wherein the converting comprises:
reacting the compound of formula VII with(S)-2-aminobutanamide or its salt or alkyl(S)-2-aminobutanoate in a first solvent under basic conditions at a temperature in the range 25° C. to 200° C. to produce a compound of formula IX,

OG Complex Work Unit Chemistry
isolating the compound of formula IX, and
converting the isolated compound of formula IX to brivaracetam XII in a second solvent at a temperature in the range 25° C. to 200° C.