US 12,478,612 B2
Deuterated domperidone compositions, methods, and preparation
Catherine Pearce, Montgomery, OH (US); Jon Isaacsohn, Cincinnati, OH (US); and Piyush Patel, Garnet Valley, PA (US)
Assigned to CINDOME PHARMA, INC., Cincinnati, OH (US)
Filed by CinDome Pharma, Inc., Cincinnati, OH (US)
Filed on Jun. 20, 2022, as Appl. No. 17/844,154.
Application 17/844,154 is a division of application No. 16/621,107, granted, now 11,364,226, previously published as PCT/US2018/039928, filed on Jun. 28, 2018.
Application 16/621,107 is a continuation in part of application No. 15/639,431, filed on Jun. 30, 2017, granted, now 10,266,516, issued on Apr. 23, 2019.
Prior Publication US 2024/0091199 A1, Mar. 21, 2024
Int. Cl. A61K 31/4184 (2006.01); A61K 31/454 (2006.01)
CPC A61K 31/4184 (2013.01) [A61K 31/454 (2013.01)] 8 Claims
 
1. A method of preparing deuterated domperidone Compound 1:

OG Complex Work Unit Chemistry
wherein, each R is, independently, H or D;
the method comprising:
(i) reacting a 1,2-diaminobenzene having 0-4 deuterium atoms with tetraethyl orthocarbonate;
(ii) reacting the product of step (i) with a 1,3-bifunctional propyl derivative containing 0-6 deuteriums, to produce an intermediate; and
(iii) reacting the intermediate with 5-chloro-1-(4-piperidyl)-1H-benzimidazol-2 (3H)-one;
wherein at least one R in Compound 1 is D.