HETEROAROMATIC COMPOUNDS AS BTK INHIBITORS

1 . A compound of the formula (I)

wherein

A ring is:

R 1 is N(R 3 ) 2 or hydrogen;

Cy is aryl or heteroaryl each is substituted by R 2 and optionally substituted by halogen, halo C 1-4 alkyl, C 1-4 alkyl and C 1-4 alkoxy;

R 2 is chosen from:

L-Ar, C 1-6 alkyl and C 1-6 alkoxy, each Ar, C 1-6 alkyl and C 1-6 alkoxy are optionally substituted by halogen, halo C 1-4 alkyl, C 1-4 alkyl, R 3 —S(O) m —, —CN, —C(O)—N(R 3 ) 2 or C 1-4 alkoxy;

L is a linker chosen from a bond, O, >C(O), —(CH 2 ) n —, —O—(CH 2 ) n —, —N(R 3 )—, —N(R 3 )—(CH 2 ) n —, —(CH 2 ) n —N(R 3 )—, —C(O)—N(R 3 )—, —C(O)—N(R 3 )—(CH 2 ) n —, —N(R 3 )—C(O)—N(R 3 )—, —N(R 3 )—C(O)—, —S(O) m —N(R 3 )— and —N(R 3 )—S(O) m —, wherein the —CH 2 — in each L can have 1-2 hydrogens replaced by C 1-3 alkyl, said C 1-3 alkyl groups can optionally cyclize to form a C 3-6 cycloalkyl ring;

Ar is carbocycle, heterocycyl or heteroaryl;

X 1 is a linker chosen from a bond, —(CH 2 ) n —;

Y is chosen from C 7 -C 10 spirocycle optionally containing 0-1 ring nitrogen atoms, a nitrogen containing mono- or bi-cyclic heterocycle, carbocycle, aryl, each substituted by one R 4 ;

R 4 is

 wherein R 5 cannot be hydrogen,

each n is independently 1-4;

each m is independently 0-2;

each R 3 is independently chosen from hydrogen or C 1-4 alkyl;

each R 5 is independently chosen from hydrogen, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylC 1-4 alkoxy, —(CH 2 ) n -heterocycle and heterocycle each heterocycle optionally substituted by halogen, OH or R 3 —S(O) m —;

each group defined above for Cy, R 1 -R 5 , X 1 and Y can be where possible partially or fully halogenated;

or a pharmaceutically acceptable salt thereof.

2 . The compound according to claim 1 and wherein

A ring is:

or a pharmaceutically acceptable salt thereof.

3 . The compound according to claim 2 and wherein

Cy is phenyl, pyridinyl, pyridazinyl, pyrimidinyl or pyrazinyl each is substituted by R 2 and optionally substituted by F, Cl or C 1-4 alkoxy;

R 2 is chosen from:

L-Ar and C 1-3 alkoxy, each Ar and C 1-3 alkoxy are optionally substituted by F, Cl, C 1-4 alkyl, R 3 —S(O) 2 —, —CN, —C(O)—NH(R 3 ) or C 1-3 alkoxy;

L is a linker chosen from a bond, O, >C(O), —CH 2 —, —O—CH 2 —, —NH—, —NH—CH 2 —, —CH 2 —NH—, —C(O)—NH—CH 2 —, —NH—C(O)—NH— and —N(R 3 )—S(O) m —;

Ar is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoxazolyl, indolyl, isoindolyl, benzofuranyl, benzimidazolyl, benzothiazolyl, piperidinyl, piperazinyl or pyrrolidinyl

or a pharmaceutically acceptable salt thereof.

4 . The compound according to claim 3 and wherein

Cy is phenyl or pyridinyl, each is substituted by R 2 and optionally substituted by F, Cl or C 1-2 alkoxy;

R 2 is chosen from:

L-Ar and C 1-3 alkoxy, each Ar and C 1-3 alkoxy are optionally substituted by F, Cl, C 1-4 alkyl, CH 3 —S(O) 2 —, —CN, —C(O)—NH(R 3 ) or C 1-2 alkoxy;

L is a linker chosen from a bond, O, >C(O), —CH 2 —, —O—CH 2 —, —NH—, —NH—CH 2 —, —CH 2 —NH—, —C(O)—NH—CH 2 —, —NH—C(O)—NH— and —N(R 3 )—S(O) m —;

Ar is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, benzoxazolyl, indolyl, isoindolyl, benzofuranyl, benzimidazolyl, benzothiazolyl or piperidinyl

or a pharmaceutically acceptable salt thereof.

5 . The compound according to claim 4 and wherein

Cy is phenyl or pyridinyl, each is substituted by R 2 and optionally substituted by F, Cl or C 1-2 alkoxy;

R 2 is chosen from:

L-Ar and C 1-3 alkoxy, each Ar and C 1-3 alkoxy are optionally substituted by F, Cl, C 1-4 alkyl, CH 3 —S(O) 2 —, —CN, —C(O)—NH(CH 3 ) or C 1-2 alkoxy;

L is a linker chosen from a bond, O, >C(O), —CH 2 —, —O—CH 2 —, —NH—, —NH—CH 2 —, —CH 2 —NH—, —C(O)—NH—CH 2 —, —NH—C(O)—NH— and —N(H)—S(O) 2 —;

Ar is phenyl, pyridinyl, benzoxazolyl or piperidinyl

or a pharmaceutically acceptable salt thereof.

6 . The compound according to claim 5 and wherein

X 1 is a linker chosen from a bond and —(CH 2 ) n —;

Y is chosen from:

a spirocycle chosen from

a heterocycle chosen from piperidinyl and pyrrolidinyl;

and phenyl each heterocycle or phenyl substituted by one R 4 ;

R 4 is

 wherein R 5 cannot be hydrogen,

 each R 4 is optionally halogenated;

each R 5 is independently chosen from hydrogen, C 1-3 alkyl, halo C 1-3 alkyl, C 1-3 alkylC 1-3 alkoxy, —CH 2 -heterocycle and heterocycle each heterocycle optionally substituted by F, Cl, OH and CH 3 —S(O) 2 — and each heterocycle chosen from pyrrolidinyl, piperidinyl, morpholinyl and 1,4-oxazepane,

or a pharmaceutically acceptable salt thereof.

7 . The compound according to claim 6 and wherein

X 1 is a linker chosen from a bond and —(CH 2 ) n —;

Y is chosen from:

a spirocycle chosen from

a heterocycle chosen from piperidinyl and pyrrolidinyl;

and phenyl each heterocycle or phenyl substituted by one R 4 ;

R 4 is

 X 3 =halogen or hydrogen,

each R 5 is independently chosen from hydrogen, C 1-3 alkyl, —CF 3 , C 1-3 alkylC 1-3 alkoxy, —CH 2 -heterocycle and heterocycle each heterocycle optionally substituted by F, Cl, OH and CH 3 —S(O) 2 — and each heterocycle chosen from pyrrolidinyl, piperidinyl and 1,4-oxazepane,

or a pharmaceutically acceptable salt thereof.

8 . The compound according to claim 1 and wherein

Cy is

or a pharmaceutically acceptable salt thereof.

9 . The compound according to claim 8 and wherein

X—Y═

a pharmaceutically acceptable salt thereof.

10 . The compound according to claim 9 and wherein

A ring is:

 or a pharmaceutically acceptable salt thereof.

11 . The compound according to claim 9 and wherein

A ring is:

 or a pharmaceutically acceptable salt thereof.

12 . The compound according to claim 9 and wherein

A ring is:

 or a pharmaceutically acceptable salt thereof.

13 . The compound according to claim 9 and wherein

A ring is:

 or a pharmaceutically acceptable salt thereof.

14 . The compound according to claim 2 and wherein

R 2 is

L-Ar;

L is a linker chosen from a bond, 0, and —O—(CH 2 ) n —;

n is 1-3;

Ar is carbocycle or heterocycle.

15 . The compound according to claim 14 and wherein

Ar is C 3-5 cycloalkyl or tetrahydrofuranyl;

n=1.

16 . The compound according to claim 15 and wherein

L-Ar is

17 . The compound according to claim 2 and wherein

R 2 is:

 —OCH 2 CH 3 , —OCH 2 CH 2 CH 3 , —OCH 3 —OCF 3 or —OCH 2 CF 3 .

18 . A compound chosen from:

or the pharmaceutically acceptable salts thereof.

19 . A compound chosen from:

or the pharmaceutically acceptable salts thereof.

20 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

21 . A method of treating a disease chosen from rheumatoid arthritis, systemic lupus erythromatosis, scleroderma, asthma, allergic rhinitis, allergic eczema, B cell lymphoma, multiple sclerosis, juvenile rheumatoid arthritis, juvenile idiopathic arthritis, inflammatory bowel disease, graft versus host disease, psoriatic arthritis, ankylosing spondylitis and uveitis, comprising administering to a patient a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.