US 11,731,947 B2
Deuterated antimicrobial compounds
Marvin J. Miller, South Bend, IN (US); Viktor Krchnak, South Bend, IN (US); and Rui Liu, South Bend, IN (US)
Assigned to University of Notre Dame du Lac, South Bend, IN (US)
Appl. No. 17/602,401
Filed by University of Notre Dame du Lac, South Bend, IN (US)
PCT Filed Apr. 3, 2020, PCT No. PCT/US2020/026618
§ 371(c)(1), (2) Date Oct. 8, 2021,
PCT Pub. No. WO2020/210125, PCT Pub. Date Oct. 15, 2020.
Claims priority of provisional application 62/832,010, filed on Apr. 10, 2019.
Prior Publication US 2022/0204463 A1, Jun. 30, 2022
Int. Cl. C07D 279/08 (2006.01); C07D 491/113 (2006.01)
CPC C07D 279/08 (2013.01) [C07D 491/113 (2013.01)] 20 Claims
 
1. A method for forming a deuterated compound of Formula IA, IB, or IC:

OG Complex Work Unit Chemistry
or an azoxy dimer or salt thereof;
wherein
R1 is 2-(C1-C6)alkyl-1,4-dioxa-8-azaspiro[4.5]decan-8-yl or 4-((C3-C6)cycloalkyl methyl)piperazin-1-yl;
R2 is halo, cyano, —(C1-C3)alkyl, or —O(C1-C3)alkyl, wherein —(C1-C3)alkyl or —O(C1-C3)alkyl has 2 to 7 halo substituents;
R3 and R4 are independently H, D, halo, hydroxyl, cyano, —(C1-C6)alkyl; and
R5 is H, D, halo, hydroxyl, cyano, —(C1-C6)alkyl;
comprising:
a) reacting a deuteride reducing agent and a compound of Formula IA wherein R3 and R4 are H to form a reduced intermediate; and
b) reacting the reduced intermediate and an oxidizing agent to form a compound of Formula IA wherein at least one of R3 or R4 is D; or
c) reacting the reduced intermediate and a protic reagent to form a compound of Formula IB or IC;
wherein the deuterated compound of Formula IA, IB, or IC is thereby formed.