5-HT3 receptor modulators, methods of making, and use thereof

A compound of formula II:

• wherein:
• represents an optional double bond;
• Q is a saturated, bicyclic, heterocyclic amine, wherein the saturated, bicyclic, heterocyclic amine is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C1-C3 alkyl, halogen, —CN, —OR7, and —NR7R8;
• X is CH, CH2, CR2, C(R2)2, N, NH, C═O, or SO2;
• Y is CH, CH2, CR2, C(R2)2, N, NH, NR3, O, or C═O;
• Z is C or N;
• R1 is individually selected at each location from the group consisting of H, halogen, —OR4, —NR4R5, —NR4C(O)R5, —NR4C(O)2R5, —NR5C(O)NR5R6, —S(O)qR5, —CN, —C(O)R5, —C(O)NR4R5, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R2 is individually selected at each location from the group consisting of H, halogen, —OR4, —NR4R5, —NR4C(O)R5, —NR4C(O)2R5, —NR5C(O)NR5R6, —S(O)qR5, —CN, —C(O)R5, —C(O)NR4R5, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R3 is selected from the group consisting of H, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R4 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• R5 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• or
• R4 and R5 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• R6 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
• R7 and R8 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• n is 0, 1, or 2, with the provisos that:
• (1) when Z is N, then n is 1 or 2;
• and (2) when Z is C, then n is 0, 1, or 2;
• p is 0, 1, 2, or 3;
• q is 0, 1, or 2;
• and
• wherein heteroaryl is an aromatic monocyclic or multi-cyclic ring system of 5 to 14 ring atoms in which one or more atoms in the ring system are nitrogen, oxygen, or sulfur;
• or a pharmaceutically acceptable salt thereof.

A process of preparing a product compound of formula Ia:

• wherein:
• Q is a saturated, bicyclic, heterocyclic amine comprising at least two atoms between the amide nitrogen of the compound of formula I and any amine nitrogen of Q and wherein the saturated, bicyclic, heterocyclic amine is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C1-C3 alkyl, halogen, —CN, —OR7, and —NR7R8;
• R1 is individually selected at each location from the group consisting of H, halogen, —OR4, —NR4R5, —NR4C(O)R5, —NR4C(O)2R5, —NR5C(O)NR5R6, —S(O)qR5, —CN, —C(O)R5, —C(O)NR4R5, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R4 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• R5 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• or
• R4 and R5 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• R6 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
• R7 and R8 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• n is 1 or 2;
• p is 0, 1, 2, or 3;
• and
• q is 0, 1, or 2;
• wherein heteroaryl is an aromatic monocyclic or multi-cyclic ring system of 5 to 14 ring atoms in which one or more atoms in the ring system are nitrogen, oxygen, or sulfur;
• said process comprising:
• treating a first intermediate compound of formula III:
• wherein M is H or a counterion, under amide bond formation conditions effective to produce the product compound.

A process of preparing a product compound of formula Ib:

• wherein:
• Q is a saturated, bicyclic, heterocyclic amine comprising at least two atoms between the amide nitrogen of the compound of formula I and any amine nitrogen of Q and wherein the saturated, bicyclic, heterocyclic amine is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C1-C3 alkyl, halogen, —CN, —OR7, and —NR7R8;
• R1 is individually selected at each location from the group consisting of H, halogen, —OR4, —NR4R5, —NR4C(O)R5, —NR4C(O)2R5, —NR5C(O)NR5R6, —S(O)qR5, —CN, —C(O)R5, —C(O)NR4R5, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R4 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• R5 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• or
• R4 and R5 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• R6 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
• R7 and R8 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• n is 1 or 2;
• p is 0, 1, 2, or 3;
• and
• q is 0, 1, or 2;
• wherein heteroaryl is an aromatic monocyclic or multi-cyclic ring system of 5 to 14 ring atoms in which one or more atoms in the ring system are nitrogen, oxygen, or sulfur;
• said process comprising:
• treating a first intermediate compound of formula IV:
• wherein M is H or a counterion, under amide bond formation conditions effective to produce the product compound.

A process of preparing a product compound of formula Ic:

• wherein:
• Q is a saturated, bicyclic, heterocyclic amine comprising at least two atoms between the amide nitrogen of the compound of formula I and any amine nitrogen of Q and wherein the saturated, bicyclic, heterocyclic amine is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C1-C3 alkyl, halogen, —CN, —OR7, and —NR7R8;
• X is CH, CH2, CR2, C(R2)2, N, NH, C═O, or SO2;
• R1 is individually selected at each location from the group consisting of H, halogen, —OR4, —NR4R5, —NR4C(O)R5, —NR4C(O)2R5, —NR5C(O)NR5R6, —S(O)qR5, —CN, —C(O)R5, —C(O)NR4R5, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R2 is individually selected at each location from the group consisting of H, halogen, —OR4, —NR4R5, —NR4C(O)R5, —NR4C(O)2R5, —NR5C(O)NR5R6, —S(O)qR5, —CN, —C(O)R5, —C(O)NR4R5, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R4 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• R5 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• or
• R4 and R5 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• R6 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
• R7 and R8 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• n is 1 or 2;
• p is 0, 1, 2, or 3;
• and
• q is 0, 1, or 2;
• wherein heteroaryl is an aromatic monocyclic or multi-cyclic ring system of 5 to 14 ring atoms in which one or more atoms in the ring system are nitrogen, oxygen, or sulfur;
• said process comprising:
• treating a first intermediate compound of formula V:
• wherein M is H or a counterion, under amide bond formation conditions effective to produce the product compound.

A process of preparing a product compound of formula IIa:

• wherein:
• Q is a saturated, bicyclic, heterocyclic amine, wherein the saturated, bicyclic, heterocyclic amine is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C1-C3 alkyl, halogen, —CN, —OR7, and —NR7R8;
• R1 is individually selected at each location from the group consisting of H, halogen, —OR4, —NR4R5, —NR4C(O)R5, —NR4C(O)2R5, —NR5C(O)NR5R6, —S(O)qR5, —CN, —C(O)R5, —C(O)NR4R5, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R4 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• R5 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• or
• R4 and R5 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• R6 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
• R7 and R8 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• n is 0, 1, or 2;
• p is 0, 1, 2, or 3;
• and
• q is 0, 1, or 2;
• wherein heteroaryl is an aromatic monocyclic or multi-cyclic ring system of 5 to 14 ring atoms in which one or more atoms in the ring system are nitrogen, oxygen, or sulfur;
• said process comprising:
• treating a first intermediate compound of formula VI:
• wherein M is H or a counterion, under amide bond formation conditions effective to produce the product compound.

A process of preparing a product compound of formula IIb:

• wherein:
• Q is a saturated, bicyclic, heterocyclic amine, wherein the saturated, bicyclic, heterocyclic amine is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C1-C3 alkyl, halogen, —CN, —OR7, and —NR7R8;
• R1 is individually selected at each location from the group consisting of H, halogen, —OR4, —NR4R5, —NR4C(O)R5, —NR4C(O)2R5, —NR5C(O)NR5R6, —S(O)qR5, —CN, —C(O)R5, —C(O)NR4R5, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R4 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• R5 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• or
• R4 and R5 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• R6 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
• R7 and R8 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• n is 0, 1, or 2;
• p is 0, 1, 2, or 3;
• and
• q is 0, 1, or 2;
• wherein heteroaryl is an aromatic monocyclic or multi-cyclic ring system of 5 to 14 ring atoms in which one or more atoms in the ring system are nitrogen, oxygen, or sulfur;
• said process comprising:
• treating a first intermediate compound of formula VII:
• wherein M is H or a counterion, under amide bond formation conditions effective to produce the product compound.

A process of preparing a product compound of formula IIc:

• wherein:
• Q is a saturated, bicyclic, heterocyclic amine, wherein the saturated, bicyclic, heterocyclic amine is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from the group consisting of C1-C3 alkyl, halogen, —CN, —OR7, and —NR7R8;
• R1 is individually selected at each location from the group consisting of H, halogen, —OR4, —NR4R5, —NR4C(O)R5, —NR4C(O)2R5, —NR5C(O)NR5R6, —S(O)qR5, —CN, —C(O)R5, —C(O)NR4R5, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR7, —NR7R8, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR7, or —NR7R8;
• R4 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• R5 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• or
• R4 and R5 are taken together with the nitrogen to which they are attached to form a five- to seven-membered heterocyclic ring, which comprises from 1 to 2 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted from 1 to 4 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• R6 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
• R7 and R8 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R6, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• n is 1 or 2;
• p is 0, 1, 2, or 3;
• and
• q is 0, 1, or 2;
• wherein heteroaryl is an aromatic monocyclic or multi-cyclic ring system of 5 to 14 ring atoms in which one or more atoms in the ring system are nitrogen, oxygen, or sulfur;
• said process comprising:
• treating a first intermediate compound of formula VIII:
• wherein M is H or a counterion, under amide bond formation conditions effective to produce the product compound.