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US 12,215,114 B2Granted
Processes and intermediates for producing diazaspiro lactam compounds
AssigneeNaurex, Inc.
InventorsDanny T. Dinh, William R. Perrault, Khalid Diker
Life of this patent
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Abstract
Processes for producing diazaspiro lactam compounds and intermediates useful in the processes.
Claims20
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:
- 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.
16 more elements
A compound of formula II:
- 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-C3 alkyl), 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.
16 more elements
A compound of formule III.
- 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;
- 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-C3 alkyl), 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.
15 more elements
Dependencies are inferred from the claim text.