Cyclohexyl azetidine derivatives as JAK inhibitors

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

X is CR 1 or N;

Y is CR 2 or N;

W is CR 3 or N;

Z is CR 4 or N;

V is CR 5 or N;

wherein the 6-membered aromatic ring formed by carbon atom, X, Y, W, Z, and V has 0, 1, or 2 nitrogen ring members;

R 1 , R 2 , R 3 , R 4 , and R 5 are each independently selected from H, halo, CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, Cy, —C 1-3 alkylene-Cy, OR a , NR e R f , SR b , S(═O) 2 R b , S(═O) 2 NR e R f , C(═O)R b , C(═O)OR a , C(═O)NR e R f , OC(═O)R b , OC(═O)NR e R f , NR c C(═O)R d , NR c C(═O)OR d , NR c S(═O) 2 R d , NR c S(═O) 2 NR e R f , and CR o R p OR a1 , and CR o R p NR e1 R f1 ; wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3 independently selected R x groups;

R 6 is F, methyl, —OH, or —OCH 3 ;

each Cy is independently selected from 3-6-membered monocyclic cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, phenyl, and 5-6 membered monocyclic heteroaryl, which are each optionally substituted by 1, 2, or 3 independently selected Regroups;

each R a , R c , R d , R e , and R f is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, Cy 1 , and —C 1-3 alkylene-Cy 1 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 independently selected R h groups; or

each R e and R f , together with the nitrogen atom to which they are attached, form a 4-6 membered monocyclic heterocycloalkyl ring; which is optionally substituted with 1, 2, or 3 independently selected R g groups;

each R b is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, Cy 1 , and —C 1-3 alkylene-Cy 1 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 independently selected R h groups;

R o and R p , taken together with the carbon atom to which they are attached, form a 3-4 membered monocyclic cycloalkyl ring;

each Cy 1 is independently selected from 3-6-membered monocyclic cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, phenyl, and 5-6 membered monocyclic heteroaryl, which are each optionally substituted by 1, 2, or 3 independently selected R g groups;

each R g is independently selected from halo, CN, hydroxy, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, hydroxyl-C 1-4 alkyl, C 1-4 alkoxy-C 1-4 alkyl, cyano-C 1-4 alkyl, amino, C 1-4 alkylamino, di-C 1-4 -alkylamino, carbamyl, C 1-4 alkylcarbamyl, di(C 1-4 alkyl)carbamyl, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonyloxy, C 1-4 alkylsulfonyl, C 1-4 alkylcarbonylamino, C 1-4 alkylsulfonylamino, aminosulfonyl, C 1-4 alkylaminosulfonyl, di-C 1-4 alkylaminosulfonyl, aminosulfonylamino, C 1-4 alkylaminosulfonylamino, and di-C 1-4 alkylaminosulfonylamino;

each R h is independently selected from halo, CN, hydroxy, C 1-4 alkoxy, C 1-4 haloalkoxy, hydroxyl-C 1-4 alkyl, C 1-4 alkoxy-C 1-4 alkyl, cyano-C 1-4 alkyl, amino, C 1-4 alkylamino, carbamyl, C 1-4 alkylcarbamyl, di(C 1-4 alkyl)carbamyl, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonyloxy, C 1-4 alkylcarbonylamino, C 1-4 alkylsulfonylamino, aminosulfonyl, C 1-4 alkylaminosulfonyl, alkylaminosulfonyl, aminosulfonylamino, C 1-4 alkylaminosulfonylamino, and di-C 1-4 alkylaminosulfonylamino;

each RX group is independently selected from halo, CN, NO 2 , OR a1 , NR e1 R f1 , SR b1 , S(═O) 2 R b1 , S(═O) 2 NR e1 R f1 , C(═O)R b1 , C(═O)OR a1 , C(═O)NR e1 R f1 , OC(═O)R b1 , OC(═O)NR e1 R f1 , NR c1 C(═O)R d1 , NR c1 C(═O)OR d1 , NR c1 S(═O) 2 R d1 , and NR c1 S(═O) 2 NR e1 R f1 ;

each R a1 , R c1 , R d1 , R e1 and R f1 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, Cy 2 , and —C 1-3 alkylene-Cy 2 ; wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3 independently selected R k groups; or

each R e1 and R f1 , together with the nitrogen atom to which they are attached, forms a 4-6 membered monocyclic heterocycloalkyl ring; which is optionally substituted with 1, 2, or 3 independently selected R m groups;

each R b1 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, Cy 2 , and —C 1-3 alkylene-Cy 2 ; wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3 independently selected R k groups;

each Cy 2 is independently selected from 3-6-membered monocyclic cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, phenyl, and 5-6 membered monocyclic heteroaryl, which are each optionally substituted by 1, 2, or 3 independently selected R m groups;

each R k is independently selected from halo, CN, hydroxy, C 1-4 alkoxy, C 1-4 haloalkoxy, hydroxyl-C 1-4 alkyl, C 1-4 alkoxy-C 1-4 alkyl, cyano-C 1-4 alkyl, amino, C 1-4 alkylamino, carbamyl, C 1-4 alkylcarbamyl, di(C 1-4 alkyl)carbamyl, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonyloxy, C 1-4 alkylcarbonylamino, C 1-4 alkylsulfonyl, C 1-4 alkylsulfonylamino, aminosulfonyl, C 1-4 alkylaminosulfonyl, alkylaminosulfonyl, aminosulfonylamino, C 1-4 alkylaminosulfonylamino, and di-C 1-4 alkylaminosulfonylamino;

each R m is independently selected from halo, CN, hydroxy, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, hydroxyl-C 1-4 alkyl, C 1-4 alkoxy-C 1-4 alkyl, cyano-C 1-4 alkyl, amino, C 1-4 alkylamino, carbamyl, C 1-4 alkylcarbamyl, di(C 1-4 alkyl)carbamyl, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonyloxy, C 1-4 alkylsulfonyl, C 1-4 alkylcarbonylamino, C 1-4 alkylsulfonylamino, aminosulfonyl, C 1-4 alkylaminosulfonyl, alkylaminosulfonyl, aminosulfonylamino, C 1-4 alkylaminosulfonylamino, and di-C 1-4 alkylaminosulfonylamino; and

n is 0, 1, or 2.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , and R 5 are each independently selected from H, —CF 3 , —CH 2 R x , and —C(CH 3 ) 2 R x .

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein each R x group is independently selected from OR a1 and NR e1 R f1 .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R a1 , R c1 , R d1 , R e1 , and R f1 is independently selected from H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, Cy 2 , and —C 1-3 alkylene-Cy 2 ; wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3 independently selected R k groups; or

each R e1 and R f1 , together with the nitrogen atom to which they are attached, forms a 4-6 membered monocyclic heterocycloalkyl ring; which is optionally substituted with 1, 2, or 3 independently selected R m groups.

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein each Cy 2 is independently selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydrofuran-2-yl, and 1H-imidazol-4-yl, which are each optionally substituted by 1, 2, or 3 independently selected R m groups.

6. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein each R m is independently selected from halo, hydroxy, C 1-4 alkoxy, hydroxyl-C 1-4 alkyl, and C 1-4 alkoxy-C 1-4 alkyl.

7. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein each R k is independently selected from hydroxy, C 1-4 alkoxy, hydroxyl-C 1-4 alkyl, and C 1-4 alkoxy-C 1-4 alkyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the 6-membered aromatic ring formed by carbon atom, X, Y, W, Z, and V is selected from:

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

X is N;

Y is CR 2 ;

W is CR 3 or N;

Z is CR 4 ;

V is CR 5 ;

R 2 , R 3 , R 4 , and R 5 are each independently selected from H, halo, CN, C 1-6 alkyl, C 1-6 haloalkyl, Cy, OR a , C(═O)OR a , and C(═O)NR e R f ; wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3 independently selected R x groups;

each Cy is independently selected from 3-6-membered monocyclic cycloalkyl optionally substituted by 1, 2, or 3 independently selected R g groups;

each R a , R e , and R f is, independently, H or C 1-6 alkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 independently selected R h groups; or

each R e and R f , together with the nitrogen atom to which they are attached, form a 4-6 membered monocyclic heterocycloalkyl ring;

each R g is independently selected from hydroxy and hydroxyl-C 1-4 alkyl;

each R h is independently selected from halo, hydroxy, and C 1-4 alkoxy;

each R x group is independently selected from OR a1 and NR e1 R f1 ;

each R a1 , R e1 and R f1 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, Cy 2 , and —C 1-3 alkylene-Cy 2 ; wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3 independently selected R k groups; or

each R e1 and R f1 , together with the nitrogen atom to which they are attached, forms a 4-6 membered monocyclic heterocycloalkyl ring; which is optionally substituted with 1, 2, or 3 independently selected R m groups;

each Cy 2 is independently selected from 3-6-membered monocyclic cycloalkyl, 4-6 membered monocyclic heterocycloalkyl, and 5-6 membered monocyclic heteroaryl, which are each optionally substituted by 1, 2, or 3 independently selected R m groups;

each R k is independently selected from hydroxy, C 1-4 alkoxy, hydroxyl-C 1-4 alkyl, and C 1-4 alkoxy-C 1-4 alkyl; and

each R m is independently selected from halo, hydroxy, C 1-4 alkoxy, hydroxyl-C 1-4 alkyl, and C 1-4 alkoxy-C 1-4 alkyl.

10. The compound of claim 1 , having Formula II:

or a pharmaceutically acceptable salt thereof.

11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein:

R 2 is C 1-3 haloalkyl;

R 4 is selected from —CH 2 OH, —C(CH 3 ) 2 OH, and —CH 2 NR e1 R f1 ;

R e1 is H or C 1-4 alkyl;

R f1 is H, C 1-6 alkyl, C 1-6 haloalkyl, Cy 2 , or —C 1-2 alkylene-Cy 2 ; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 groups selected from —OH and —OCH 3 ;

or R e1 and R f1 together with the nitrogen atom to which they are attached form a 4-6-membered monocyclic heterocycloalkyl ring, which is optionally substituted by one —F, —OH, or —CH 2 OH group; and

Cy 2 is cyclopropyl, cyclobutyl, 5-membered monocyclic heterocycloalkyl, or 5-membered monocyclic heteroaryl; each of which is optionally substituted by a —CH 2 OH group.

12. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein:

R 2 is C 1-3 haloalkyl;

R 4 is selected from —CH 2 OH, —C(CH 3 ) 2 OH, and —CH 2 NR e1 R f1 wherein

R e1 is H, methyl or ethyl; and

R f1 is H, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, cyclopropyl, cyclobutyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl, 3-methoxypropyl, 2-hydroxy-1-methylethyl, 2-methoxy-1-methylethyl, 2-hydroxy-2-methylethyl, 2-hydroxy-2,2-dimethylethyl, 2,3-dihydroxypropyl, cyclopropylmethyl, (1-(hydroxymethyl)cyclopropyl)methyl, 2-(hydroxymethyl)tetrahydrofuran-2-yl, or 1H-imidazol-4-ylethyl; or

R e1 and R f1 , together with the nitrogen atom to which they are attached, form a group selected from azetidinyl, 3-hydroxy-azetidinyl, 3-fluoro-azetidinyl, pyrrolidinyl, 3-hydroxypyrrolidinyl, 3-fluoropyrrolidinyl, 2-(hydroxymethyl)pyrrolidinyl, and piperidinyl.

13. The compound of claim 1 , having Formula III:

or a pharmaceutically acceptable salt thereof.

14. The compound of claim 1 , having Formula IV:

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 , having Formula V:

or a pharmaceutically acceptable salt thereof.

16. The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein:

R 4 is selected from —CH 2 OH, —C(CH 3 ) 2 OH, —CH 2 NR e1 R f1 and C(═O)NR e R f ;

or R 4 is —CH 2 -pyrazolyl or —CH 2 -imidazolyl;

R e1 is H, methyl or ethyl;

R f1 is H, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-hydroxy-1-methylethyl, or cyclopropylmethyl; or

R e1 and R f1 , together with the nitrogen atom to which they are attached, form a group selected from azetidinyl, 3-hydroxy-azetidinyl, 3-fluoro-azetidinyl, 3-cyano-azetidinyl, pyrrolidinyl, 3-hydroxypyrrolidinyl, 3-fluoropyrrolidinyl, 2-(hydroxymethyl)pyrrolidinyl, piperidinyl, 4-hydroxypiperidinyl, and 3-methyloxetan-3-yl;

R e is H or methyl; and

R f is H, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, or cyclobutyl; or

R e and R f , together with the nitrogen atom to which they are attached, form a group selected from azetidinyl, 3-hydroxy-azetidinyl, 3-fluoro-azetidinyl, 3-cyano-azetidinyl, pyrrolidinyl, 3-hydroxypyrrolidinyl, 3-fluoropyrrolidinyl, 2-(hydroxymethyl)pyrrolidinyl, and piperidinyl.

17. The compound of claim 1 , having Formula III-A:

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 17 , wherein R a1 is H, methyl or ethyl.

19. A compound of claim 1 , selected from:

{1-(cis-4-{[6-[(dimethylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(hydroxymethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(aminomethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(methylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(ethylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(isopropylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(cyclopropylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[ethyl(methyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(cyclopropylmethyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(cyclobutylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(2-hydroxyethyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(2-hydroxyethyl)(methyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[ethyl(2-hydroxyethyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

[3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-1-(cis-4-{[6-{[(2,2,2-trifluoroethyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)azetidin-3-yl]acetonitrile;

{1-(cis-4-{[6-{[(2-fluoroethyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-({[(1 S)-2-hydroxy-1-methylethyl]amino}methyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-({[(1R)-2-hydroxy-1-methylethyl]amino}methyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-({[(2S)-2-hydroxypropyl]amino}methyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-({[(2R)-2-hydroxypropyl]amino}methyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(2-hydroxy-2-methylpropyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(3-hydroxypropyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(2-methoxyethyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(azetidin-1-ylmethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(3-hydroxyazetidin-1-yl)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(pyrrolidin-1-ylmethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

[3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-1-(cis-4-{[6-({[(2S)-tetrahydrofuran-2-ylmethyl]amino}methyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)azetidin-3-yl]acetonitrile;

{1-(cis-4-{[6-{[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(piperidin-1-ylmethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(3 S)-3-fluoropyrrolidin-1-yl]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(propylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(2,3-dihydroxypropyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(butylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(isobutylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[butyl(methyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[(3-fluoroazetidin-1-yl)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[({[1-(hydroxymethyl)cyclopropyl]methyl}amino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

2-(1-(cis-4-((6-(((2-(1H-imidazol-4-yl)ethyl)amino)methyl)-2-(trifluoromethyl)pyrimidin-4-yl)oxy)cyclohexyl)-3-(4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile;

{1-(cis-4-{[6-{[(3-methoxypropyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(2-methoxy-1-methylethyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(2-methoxyethyl)(methyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(1-hydroxy-1-methylethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile; and

{1-(cis-4-{[6-[(tert-butylamino)methyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

or a pharmaceutically acceptable salt thereof.

20. The compound of claim 1 , selected from:

6-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-ethyl-2-(trifluoromethyl)pyrimidine-4-carboxamide;

{1-(cis-4-{[6-(pyrrolidin-1-ylcarbonyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(2-hydroxy-1,1-dimethylethyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-{[(1-methylcyclopropyl)amino]methyl}-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

6-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-2-(trifluoromethyl)pyrimidine-4-carbonitrile;

{1-(cis-4-{[6-(2-hydroxyethoxy)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(1,2-dihydroxy-1-methylethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(1-hydroxyethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(2-hydroxy-1-methylethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(1-fluoro-1-methylethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(2-hydroxy-1,1-dimethylethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-[1-(hydroxymethyl)cyclopropyl]-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[6-(2-hydroxyethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

6-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N,N-dimethyl-2-(trifluoromethyl)pyrimidine-4-carboxamide;

6-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-ethyl-N-methyl-2-(trifluoromethyl)pyrimidine-4-carboxamide;

6-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-(2-methoxyethyl)-2-(trifluoromethyl)pyrimidine-4-carboxamide;

{1-(cis-4-{[6-(2-fluoroethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-(hydroxymethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-[(ethylamino)methyl]-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-[(methylamino)methyl]-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-[(dimethylamino)methyl]-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-(1-hydroxy-1-methylethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-{[(3-hydroxypropyl)amino]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-{[(2-hydroxy-1, 1-dimethylethyl)amino]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-[(cyclopropylamino)methyl]-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-({[(1 S)-2-hydroxy-1-methylethyl]amino}methyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-{[(2-hydroxyethyl)amino]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-({[(1R)-2-hydroxy-1-methylethyl]amino}methyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-{[(cyclopropylmethyl)amino]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-[(cyclobutylamino)methyl]-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-(azetidin-1-ylmethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-[(3-hydroxyazetidin-1-yl)methyl]-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-methyl-6-(trifluoromethyl)isonicotinamide;

2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N,N-dimethyl-6-(trifluoromethyl)isonicotinamide;

2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-(2-hydroxyethyl)-N-methyl-6-(trifluoromethyl)isonicotinamide;

2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-isopropyl-6-(trifluoromethyl)isonicotinamide;

2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-[(1S)-2-hydroxy-1-methylethyl]-6-(trifluoromethyl)isonicotinamide;

2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-[(1R)-2-hydroxy-1-methylethyl]-6-(trifluoromethyl)isonicotinamide;

2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-cyclopropyl-6-(trifluoromethyl)isonicotinamide;

2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-cyclopropyl-N-methyl-6-(trifluoromethyl)isonicotinamide;

N-(sec-butyl)-2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-6-(trifluoromethyl)isonicotinamide;

{1-(cis-4-{[4-[(3-hydroxyazetidin-1-yl)carbonyl]-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2, 3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-N-cyclobutyl-6-(trifluoromethyl)isonicotinamide;

1-[2-[(cis-4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}cyclohexyl)oxy]-6-(trifluoromethyl)isonicotinoyl]azetidine-3-carbonitrile;

{1-(cis-4-{[4-(morpholin-4-ylmethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2, 3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-{[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-{[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-{[(3 S)-3-hydroxypyrrolidin-1-yl]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-[(4-hydroxypiperidin-1-yl)methyl]-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-{[(3-methyloxetan-3-yl)amino]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-(1H-imidazol-1-ylmethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo [2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

{1-(cis-4-{[4-(1H-pyrazol-1-ylmethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile;

or a pharmaceutically acceptable salt thereof.

21. A composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

22. A method of inhibiting an activity of JAK1 comprising contacting JAK1 with a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

23. A method according to claim 22 , wherein said compound, or pharmaceutically acceptable salt thereof, is selective for JAK1 over JAK2.

24. A method of treating a myeloproliferative disorder in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein said myeloproliferative disorder is myelofibrosis, primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (Post-PV MF), post-essential thrombocythemia myelofibrosis (Post-ET MF), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), chronic myelogenous leukemia (CIVIL), chronic myelomonocytic leukemia (CMML), hypereosinophilic syndrome (HES), idiopathic myelofibrosis (IMF), or systemic mast cell disease (SMCD).

25. A compound of claim 1 , which is {1-(cis-4-{[4-[(ethylamino)methyl]-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.

26. A compound of claim 1 , which is {1-(cis-4-{[4-(1-hydroxy-1-methylethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.

27. A compound of claim 1 , which is {1-(cis-4-{[4-{[(3R)-3-hydroxypyrrolidin-1-yl]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.

28. A compound of claim 1 , which is {1-(cis-4-{[4-{[(3S)-3-hydroxypyrrolidin-1-yl]methyl}-6-(trifluoromethyl)pyridin-2-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.

29. A compound, which is {1-(cis-4-{[6-(2-hydroxyethyl)-2-(trifluoromethyl)pyrimidin-4-yl]oxy}cyclohexyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile, or a pharmaceutically acceptable salt thereof.

30. A composition, comprising a compound of claim 29 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.