US 12,215,114 B2
Processes and intermediates for producing diazaspiro lactam compounds
Danny T. Dinh, Costa Mesa, CA (US); William R. Perrault, Kalamazoo, MI (US); and Khalid Diker, Saint Leu D'esserent (FR)
Assigned to NAUREX INC., Madison, NJ (US)
Appl. No. 17/621,905
Filed by NAUREX INC., Madison, NJ (US)
PCT Filed Jun. 23, 2020, PCT No. PCT/US2020/039164
§ 371(c)(1), (2) Date Dec. 22, 2021,
PCT Pub. No. WO2020/263848, PCT Pub. Date Dec. 30, 2020.
Claims priority of provisional application 62/865,840, filed on Jun. 24, 2019.
Prior Publication US 2022/0259217 A1, Aug. 18, 2022
Int. Cl. C07D 487/10 (2006.01); C07D 207/16 (2006.01); C07D 498/04 (2006.01)
CPC C07D 487/10 (2013.01) [C07D 207/16 (2013.01); C07D 498/04 (2013.01)] 20 Claims
 
1. A process of producing a compound of formula I or a pharmaceutically acceptable salt thereof, comprising contacting a compound of formula II with a coupling agent in an organic solvent to obtain a compound of formula I or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein:
Rb is selected from H, halogen, cyano and C1-C6 alkyl;
R1 is H or C1-C6 alkyl;
R2 is H or C1-C6 alkyl;
R3 is selected from C1-C6 alkyl and C(O)OR8;
R8 is selected from C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, and —CH2—C3-C10 cycloalkyl, wherein C3-C10 cycloalkyl is optionally substituted with one, two, or three groups selected from C1-C3 alkyl;
R4 and R5 are independently selected from H, C1-C6 alkyl, X, and C1-C6 alkylene-X, wherein X is selected from:
(i) C3-C6 cycloalkyl;
(ii) heteroaryl including from 5 to 6 ring atoms wherein one, two, or three of the ring atoms are independently selected from N, NH, N(C1-C3 alkyl), O, and S;
(iii) heterocyclyl including from three to six ring atoms wherein 1, 2, or 3 of the ring atoms are independently selected from N, NH, N(C1-C3alkyl), O, and S; and
(iv) phenyl;
wherein C3-C6 cycloalkyl, heterocyclyl, heteroaryl, and phenyl are each optionally substituted with one, two, or three substituents independently selected halogen, cyano, C1-C6 alkyl, hydroxyl, and C1-C6 alkoxy:
or R4 and R5 together with the nitrogen to which they are attached form heterocyclyl including from 4 to 6 ring atoms; wherein the heterocyclyl includes not more than two ring heteroatoms (including the nitrogen atom attached to R4 and R5), and the second ring heteroatom, when present, is independently selected from N—C1-C6 alkyl, O and S; and wherein the heterocyclyl is optionally substituted with one, two, or three substituents independently selected from halogen, cyano, C1-C6 alkyl, and C1-C6 alkoxy;
R6 is selected from —OH, C1-C6 alkoxy, —OC(O)—C1-C6 alkyl, and —OC(O)phenyl; and
R7 is H or C1-C6 alkyl.