Azabicycloalkane-indole and azabicycloalkane-pyrrolo-pyridine mch-1 antagonists, methods of making, and use thereof

A process for preparation of a product compound of formula I:

• wherein
• R1 is selected from the group consisting of H, —S(O)qR6, —C(O)R6, —C(O)NR5R6, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR8, —NR8R9, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR8, or —NR8R9;
• R2 is selected from the group consisting of H, —S(O)R6, —C(O)R6, —C(O)NR5R6, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR8, —NR8R9, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR8, or —NR8R9;
• R3 is independently selected at each location from the group consisting of H, halogen, —OR5, —NR5R6, —NR5C(O)R6, —NR5C(O)2R6, —NR6C(O)NR6R7, —S(O)qR6, —CN, —C(O)R6, —C(O)NR5R6, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR8, —NR8R9, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR8, or —NR8R9;
• R4 is selected from the group consisting of H, halogen, —OR5, —NR5R6, —NR5C(O)R6, —NR5C(O)2R6, —NR6C(O)NR6R7, —S(O)qR6, —CN, —C(O)R6, —C(O)NR5R6, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR8, —NR8R9, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR8, or —NR8R9;
• R5 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R7, 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;
• R6 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;
• R7 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
• R8 and R9 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R7, 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;
• R10 is selected from the group consisting of H, halogen, —OR5, —NR5R6, —NR5C(O)R6, —NR5C(O)2R6, —NR6C(O)NR6R7, —S(O)qR6, —CN, —C(O)R6, —C(O)NR5R6, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR8, —NR8R9, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR8, or —NR8R9;
• X is CR10, C(R10)2, N, or NR10;
• Y is CR10, C, or N;
• Z is C, CH, or N;
• L is —(CH2)p—O—, —(CH2)p—, —CH═CH—, or a bond;
• B is aryl, heteroaryl, heterocyclyl, or cycloalkyl, wherein each of the aryl, heteroaryl, heterocyclyl, or cycloalkyl is optionally substituted with from 1 to 3 substituents selected from the group consisting of H, alkoxy, —S-alkyl, optionally substituted C1-C6 alkyl, halogen, —CF3, and —CN;
• n is 1 or 2;
• m is 0, 1, 2, or 3;
• p is from 1 to 4;
• q is 0, 1, or 2;
• and
• represents an optional double bond,
• said process comprising:
• treating a first intermediate compound of formula II:
• wherein Q is a halogen, under conditions effective to produce the product compound.