US 11,773,062 B2
Deuterated compounds
Peter Rands, London (GB); Ellen James, London (GB); and Tiffanie Benway, London (GB)
Assigned to Small Pharma Ltd, London (GB)
Filed by Small Pharma Ltd., London (GB)
Filed on Mar. 22, 2021, as Appl. No. 17/208,583.
Prior Publication US 2022/0081396 A1, Mar. 17, 2022
Int. Cl. C07D 209/14 (2006.01)
CPC C07D 209/14 (2013.01) [C07B 2200/05 (2013.01)] 7 Claims
 
1. A method of synthesising a compound of formula (I′):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, comprising reacting a compound of formula (II):

OG Complex Work Unit Chemistry
with LiAlH4 and/or LiAlD4, wherein the compound of formula (II) is made by:
reacting a compound of formula (III)

OG Complex Work Unit Chemistry
with two or more coupling agents to produce an activated compound; and
(ii) reacting the activated compound with an amine having the formula R2R3NH or R2R3ND, wherein:
R1′ is independently selected from —R4, —OPR, —OR4, —F, —Cl, —Br and —I;
PR is a protecting group,
n is selected from 0, 1, 2, 3 or 4;
R2 is C(xH)3;
R3 is C(xH)3 or H;
each R4 is independently selected from C1-C4alkyl; and
each xH and yH is independently protium or deuterium,
wherein a ratio of deuterium:protium in a C(xH)3 moiety in the compound of formula (I′) is greater than that found naturally in hydrogen,
or a pharmaceutically acceptable salt thereof.