US 11,753,392 B2
Method for synthesis of deuterated amide and deuterated sulfonamide
Wu Du, Sichuan (CN); Kun Wen, Sichuan (CN); Jinyun He, Sichuan (CN); Haibo Li, Sichuan (CN); Dekun Qin, Sichuan (CN); Xinghai Li, Sichuan (CN); and Yuanwei Chen, Sichuan (CN)
Assigned to HINOVA PHARMACEUTICALS INC., Sichuan (CN)
Appl. No. 17/47,380
Filed by HINOVA PHARMACEUTICALS INC., Sichuan (CN)
PCT Filed Apr. 12, 2019, PCT No. PCT/CN2019/082555
§ 371(c)(1), (2) Date Oct. 13, 2020,
PCT Pub. No. WO2019/196945, PCT Pub. Date Oct. 17, 2019.
Claims priority of application No. 201810332134.1 (CN), filed on Apr. 13, 2018.
Prior Publication US 2021/0115009 A1, Apr. 22, 2021
Int. Cl. C07D 401/04 (2006.01); C07C 231/24 (2006.01); C07D 233/02 (2006.01); C07D 401/06 (2006.01)
CPC C07D 401/04 (2013.01) [C07C 231/24 (2013.01); C07D 233/02 (2013.01); C07D 401/06 (2013.01); C07C 2601/14 (2017.05); C07C 2601/16 (2017.05)] 26 Claims
 
1. A method for synthesizing deuterated amine, comprising the steps of a first step of adding compound M, DMAP, and R3—X to a first solvent for reaction to obtain compound N; and
a second step of adding compound N, R4—NH—R5 or a salt thereof, and a base to a second solvent for reaction to obtain a deuterated amine compound I,

OG Complex Work Unit Chemistry
wherein:
L is carbonyl or sulfonyl;
R1 is

OG Complex Work Unit Chemistry
R2 is selected from the group consisting of substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
R3 is —CO—R6 or —SO2R7 and X is a leaving group,
wherein, R6 and R7 are independently selected from alkoxy, alkyl, substituted alkyl, and aryl;
R4 and R5 are independently selected from H, substituted or unsubstituted deuterated alkyl, deuterated cycloalkyl, deuterated heterocyclic group, deuterated aryl, and deuterated heteroaryl, with the proviso that R4 and R5 are not hydrogen at the same time;
wherein, in the first step, a yield for the compound N thus synthesized is 92.3%, and
wherein, in the second step, a yield for the deuterated amine compound I thus synthesized is 92.8%.