Thienopyrazine inhibitors of IRAK4 activity

1. A compound according to Formula I:

wherein:

Ring A is aryl or heterocyclyl;

n is 0, 1, 2, 3 or 4;

R 1 is independently selected from: (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, heterocyclyl, CN, halo, said alkyl, cycloalkyl and heterocyclyl optionally substituted with halo, OH, and OCH 3 ;

R 2 is H and R 3 is independently selected from: (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl and heterocyclyl each optionally substituted with one or more halo, OH, N(R b ) 2 , or morpholinyl, or R 2 and R 3 can be taken together with the nitrogen to which they are attached to form a heterocyclyl, said heterocyclyl optionally substituted with one or more substituents selected from R a ;

R a is independently selected from (C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, CF 3 , CHF 2 , OH, halo and NH 2 , said alkyl optionally substituted with (C 3 -C 6 )cycloalkyl and CF 3 ; and

R b is independently selected from H and (C 1 -C 4 )alkyl;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 of Formula I:

wherein:

Ring A is pyrazolyl, pyridinyl, thiophenyl, furanyl or phenyl;

n is 0, 1 or 2;

R 1 is independently selected from: (C 1 -C 4 )alkyl, cyclopropyl, oxadiazolyl, pyridinyl, oxazolyl, triazolyl, pyriminidyl, CN and halo, said alkyl, oxadiazolyl, pyridinyl, oxazolyl, triazolyl and pyriminidyl are optionally substituted with halo, OH, and OCH 3 ;

R 2 is H and R 3 is independently selected from: (C 1 -C 4 )alkyl, cyclohexyl, cycloheptyl, piperidinyl and azepanyl each optionally substituted with one or more F, OH, N(R b ) 2 , or morpholinyl, or R 2 and R 3 can be taken together with the nitrogen to which they are attached to form a heterocyclyl selected from piperazinyl, diazepanyl, diazabicyclooctyl, diazabicycloheptyl, diazaspirononyl, hexahydropyrrolopyrazinyl, piperidinyl, diazabicyclononyl, oxadiazabicyclodecyl and diazatricyclodecyl, said heterocyclyl optionally substituted with one or more substituents selected from R a ;

R a is independently selected from (C 1 -C 4 )alkyl, cyclopropyl, CF 3 , CHF 2 , OH, F and NH 2 , said alkyl optionally substituted with cyclopropyl and CF 3 ; and

R b is independently selected from H and methyl;

or a pharmaceutically acceptable salt thereof.

3. A compound which is selected from:

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-piperazin-1-ylthieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-hydroxycyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-[(3R)-piperidin-3-ylamino]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(1,4-diazepan-1-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(2,5-diazabicyclo[2.2.2]oct-2-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(5,8-diazaspiro[2.6]non-5-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-[(3R)-3-aminopiperidin-1-yl]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-{[(1R,2S)-2-hydroxycyclohexyl]amino}thieno[2,3-b]pyrazine-7-carboxamide;

2-(2,5-diazabicyclo[2.2.2]oct-2-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-piperazin-1-ylthieno[2,3-b]pyrazine-7-carboxamide;

2-(5,8-diazaspiro[2.6]non-5-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(1,4-diazepan-1-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(azepan-3-ylamino)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(3-chloro-1-methyl-1H-pyrazol-4-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(3-chloro-1-methyl-1H-pyrazol-4-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(3-chloro-1-methyl-1H-pyrazol-4-yl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(3-bromo-1-methyl-1H-pyrazol-4-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(3-bromo-1-methyl-1H-pyrazol-4-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(3-bromo-1-methyl-1H-pyrazol-4-yl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-[(3R)-3-aminopiperidin-1-yl]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(3-cyano-1-methyl-1H-pyrazol-4-yl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(3-bromo-1-methyl-1H-pyrazol-4-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(3-bromo-1-methyl-1H-pyrazol-4-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-[(3S)-azepan-3-ylamino]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-[(3R)-piperidin-3-ylamino]thieno[2,3-b]pyrazine-7-carboxamide;

2-[(3R)-azepan-3-ylamino]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-[(3S)-azepan-3-ylamino]-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(3-chloro-1-methyl-1H-pyrazol-4-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(3-cyano-1-methyl-1H-pyrazol-4-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(3-cyano-1-methyl-1H-pyrazol-4-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-[(3R)-azepan-3-ylamino]-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(3,8-diazabicyclo[3.2.1]oct-3-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(3,8-diazabicyclo[3.2.1]oct-3-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(3-chloro-1-methyl-1H-pyrazol-4-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-(3,8-diazabicyclo[3.2.1]oct-8-yl)-N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(3,8-diazabicyclo[3.2.1]oct-8-yl)-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(4-bromothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(1,4-diazepan-1-yl)-N-[4-(difluoromethyl)thiophen-3-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(4-bromothiophen-3-yl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(4-bromothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[4-(difluoromethyl)thiophen-3-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-bromothiophen-3-yl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-chlorothiophen-3-yl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(4-bromothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-bromothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(4-cyanothiophen-3-yl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-chlorothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(4-cyanothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[4-(difluoromethyl)thiophen-3-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[4-(difluoromethyl)thiophen-3-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-chlorothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-chlorothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-chlorothiophen-3-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-bromothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-bromothiophen-3-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(4-cyanothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(4-cyanothiophen-3-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-[4-(difluoromethyl)thiophen-3-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(4-bromothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-cyanothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-cyanothiophen-3-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-bromothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-cyanothiophen-3-yl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-(1,4-diazepan-1-yl)-N-[2-(trifluoromethyl)thiophen-3-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[2-(trifluoromethyl)thiophen-3-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[2-(trifluoromethyl)thiophen-3-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[2-(trifluoromethyl)thiophen-3-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-cyanothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-cyanothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(4-cyanothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-cyanophenyl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[2-(trifluoromethyl)phenyl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-bromophenyl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-cyanophenyl)-2-(5,8-diazaspiro[2.6]non-5-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-[(3R)-3-aminopiperidin-1-yl]-N-(2-cyanophenyl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-cyanophenyl)-2-[(3R)-piperidin-3-ylamino]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-cyanophenyl)-2-piperazin-1-ylthieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-bromophenyl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-bromophenyl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-bromophenyl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(1,4-diazepan-1-yl)-N-[2-(trifluoromethyl)phenyl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-chlorophenyl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-chlorophenyl)thieno[2,3-b]pyrazine-7-carboxamide;

2-[(3S)-azepan-3-ylamino]-N-(2-cyanophenyl)thieno[2,3-b]pyrazine-7-carboxamide;

2-[(3R)-azepan-3-ylamino]-N-(2-cyanophenyl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(2-cyanophenyl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-bromophenyl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-cyanophenyl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-cyanophenyl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-chlorophenyl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(2-chlorophenyl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-chlorophenyl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[2-(difluoromethyl)phenyl]thieno[2,3-b]pyrazine-7-carboxamide;

2-(1,4-diazepan-1-yl)-N-[2-(difluoromethyl)phenyl]thieno[2,3-b]pyrazine-7-carboxamide;

2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]-N-[2-(difluoromethyl)phenyl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(2-cyanophenyl)thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-[2-(difluoromethyl)phenyl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(4-chlorothiophen-3-yl)-2-(1,4-diazepan-1-yl)thieno[2,3-b]pyrazine-7-carboxamide;

N-(4-chlorothiophen-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

N-(4-chlorothiophen-3-yl)-2-[(1R,4R)-2,5-diazabicyclo[2.2.2]oct-2-yl]thieno[2,3-b]pyrazine-7-carboxamide;

2-{[(1R,2S)-2-aminocyclohexyl]amino}-N-(4-chlorothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide; and

2-{[(1R,2R)-2-amino-3,3-difluorocyclohexyl]amino}-N-(4-chlorothiophen-3-yl)thieno[2,3-b]pyrazine-7-carboxamide;

or a pharmaceutically acceptable salt thereof.

4. A pharmaceutical composition comprising a pharmaceutical carrier and a therapeutically effective amount of a compound of claim 1 .