Pyrrolidine orexin receptor antagonists

1. A compound of the formula Ib:

wherein:

R 1a and R 1b are independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) hydroxyl,

(4) C l-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,

(5) —O—C l-6 alkyl, which is unsubstituted or substituted with halogen, hydroxyl or phenyl,

(6) —CN, and

(7) heteroaryl, wherein heteroaryl is selected from imidazolyl, indolyl, oxazolyl, pyridyl, pyrrolyl, pyrimidinyl, tetrazolyl, and triazolyl, which is unsubstituted or substituted with halogen, hydroxyl, C 1-6 alkyl, —O—C 1-6 alkyl or —NO 2 ;

R 2 is hydrogen;

R 3 is methyl;

R 5 is selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) —CN,

(3) C 1-6 alkyl, which is unsubstituted or substituted with halogen or phenyl,

(4) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen or phenyl,

(5) —O—C 3-6 cycloalkyl, which is unsubstituted or substituted with C 1-6 alkyl, halogen or phenyl, and

(6) —(C═O )—O—C 1-6 alkyl ;

R 6 is selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) —CN,

(4) C 1-6 alkyl, which is unsubstituted or substituted with halogen or phenyl,

(5) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen or phenyl,

(6) —O—C 3-6 cycloalkyl, which is unsubstituted or substituted with C 1-6 alkyl, halogen or phenyl, and

or R 5 and R 6 may be joined together with the carbon atoms to which they are attached to form a 6-membered aromatic ring, which is unsubstituted or substituted with one or two C 1-6 alkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 5 is selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) C 1-6 alkyl, which is unsubstituted or substituted with halogen,

(4) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen, and

(5) —(C═O )—O—C 1-6 alkyl.

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 5 is selected from the group consisting of: hydrogen, fluoro, methyl, and methoxy.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 6 is selected from the group consisting of:

(1) —CN, and

(2) —O—C 1-6 alkyl, which is unsubstituted or substituted with halogen.

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein R 6 is selected from the group consisting of: —CN, methyl, methoxy, and difluoroethoxy.

6. A compound which is selected from the group consisting of:

1-(2-((2R,4R)-4-((4-(2,2-difluoroethoxy)pyridin-2-yl)amino)-2-methylpyrrolidine-1-carbonyl)phenyl)cyclobutcarbonitrile;

1-(2-((2R,4R)-4-((4-(2,2-difluoroethoxy)pyridin-2-yl)amino)-2-methylpyrrolidine-1-carbonyl)phenyl)cyclopropanecarbonitrile;

(2-(2H-tetrazol-2-yl)phenyl)((2R,4R)-4-((4-(2,2-difluoroethoxy)pyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

((2R,4R)-4-((4-(2,2-difluoroethoxy)pyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(2-(pyrimidin-2-yl)thiophen-3-yl)methanone;

((2R,4R)-4-((4-(2,2-difluoroethoxy)pyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(2-ethoxypyridin-3-yl)methanone;

((2R,4R)-4-((4-(2,2-difluoroethoxy)pyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(2,3-dihydro-1H-inden-4-yl)methanone;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-2-methyl-4-(quinolin-2-ylamino)pyrrolidin-1-yl)methanone;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-4-((4-(difluoromethyl)pyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-4-((5-fluoropyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-4-(isoquinolin-1-ylamino)-2-methylpyrrolidin-1-yl)methanone;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-2-methyl-4-((4-(trifluoromethyl)pyridin-2-yl)amino)pyrrolidin-1-yl)methanone;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-4-((4-chloropyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-2-methyl-4-((4-methylpyridin-2-yl)amino)pyrrolidin-1-yl)methanone;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-4-((4-fluoropyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)amino)-4-methoxynicotinonitrile;

2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)amino)isonicotinonitrile;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-4-((4-isopropoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-4-((4-ethoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

N-((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)-N-(4-cyanopyridin-2-yl)acetamide;

2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)(methyl)amino)isonicotinonitrile;

1-(2-((2R,4R)-4-((4-methoxypyridin-2-yl)amino)-2-methylpyrrolidine-1-carbonyl)phenyl)cyclopropanecarbonitrile;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-4-((3-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

((2R,4R)-4-((4-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(2-((methylsulfonyl)methyl)phenyl)methanone;

(2-(2H-1,2,3-triazol-2-yl)thiophen-3-yl)((2R,4R)-4-((4-(difluoromethyl)pyridin-2-yl)amino)-2-methylpyrrolidin- 1-yl)methanone;

(4-(2H-1,2,3-triazol-2-yl)thiophen-3-yl)((2R,4R)-4-((4-(difluoromethyl)pyridin-2-yl)amino)-2-methylpyrrolidin- 1-yl)methanone;

2-(((3R,5R)-1-(2-(2H-tetrazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)amino)isonicotinonitrile;

2(3R,5R)-5-methyl-1-(2-(pyrimidin-2-yl)benzoyl)pyrrolidin-3-yl)amino)isonicotinonitrile;

(2-(2H-1,2,3-triazol-2-yl)phenyl)((2R,4R)-4-((4-bromopyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

methyl 2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)amino)-4-methoxynicotinate;

ethyl 2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)amino)-4-methoxynicotinate;

methyl 2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)amino)-4-ethoxynicotinate

(2-(2H-1,2,3-Triazol-2-yl)phenyl)((2R,4R)-4-((4-bromopyridin-2-yl)(methyl)amino)-2-methylpyrrolidin-1-yl)methanone;

2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)amino)-3-methylisonicotinonitrile;

2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)(methyl)amino)-3-methylisonicotinonitrile;

methyl 2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)amino)-4-cyanonicotinate;

2-(((3R,5R)-1-(2-(2H-1,2,3-triazol-2-yl)benzoyl)-5-methylpyrrolidin-3-yl)amino)-3-methoxyisonicotinonitrile;

(3-(1H-pyrazol-1-yl)pyridin-2-yl)((2R,4R)-4-((3-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

((2R,4R)-4-((3-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(3-(4-methyl-1H-pyrazol-1-yl)pyridin-2-yl)methanone;

((2R,4R)-4-((3-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)methanone;

(3-(1H-pyrazol-1-yl)pyrazin-2-yl)((2R,4R)-4-((3-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)methanone;

((2R,4R)-4-((3-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(3-(pyridin-2-yl)pyrazin-2-yl)methanone;

((2R,4R)-4-((4-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)methanone;

((2R,4R)-4-((4-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(2-propylphenyl)methanone; and

((2S,4S)-4-((4-methoxypyridin-2-yl)amino)-2-methylpyrrolidin-1-yl)(2-(trifluoromethoxy)phenyl)methanone;

or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition which comprises an inert carrier and a compound of claim 1 or a pharmaceutically acceptable salt thereof.

8. A method for enhancing the quality of sleep in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

9. A method for treating insomnia in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.