Fused pyrimidine pyridinone compounds as JAK inhibitors

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• X is CH or N;
• R1 is selected from the group consisting of:
• are optionally substituted with 1 or 2 F,
• wherein
• is optionally substituted with 1 to 3 substituents independently selected from:
• (i) C1-6 alkoxy optionally substituted with OH,
• (ii) C1-6 alkyl, halogen, CN, OH, NRpRq, —NHCO2C1-6 alkyl, —NHSO2C1-6 alkyl, 5 membered ring heteroaryl, partially unsaturated heterocyclic,
• wherein the C1-6 alkyl is optionally substituted with NRpRq,
• wherein Rp and Rq are each independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkyl-OH, C1-6 alkyl-C1-6 alkoxy, and —C1-6 alkyl-aryl,
• (iii) a 6 membered ring heterocyclic group optionally substituted with 1 to 3 substituents independently selected from:
• (a) F, C1-6 alkyl, C1-6 alkyl-CF3, CF3, CHF2, CH2F, 3 to 8 membered ring cycloalkyl, —C1-6 alkyl-C1-6 alkoxy, —C1-6 alkyl-C3-8 cycloalkyl, SO2 linked to a 4 to 8 membered ring heterocyclic group, C1-6 alkyl substituted with a 4 to 8 membered ring heterocyclic group, —COCF3, —C(O)S—C1-6 alkyl, SO2—NHMe, SO2NMe2, SO2NRxRy, CONRxRy, CSNRxRy,
• (b) SO2C1-6 alkyl optionally substituted with C1-6 alkoxy or CN,
• (c) CO2C1-6 alkyl optionally substituted with C1-6 alkoxy,
• (d) COC1-6 alkyl optionally substituted with OH, C1-6 alkoxy, —SO2C1-6 alkyl, —SOC1-6 alkyl, —S—C1-6 alkyl, CN or —S—C1-6 alkyl,
• and wherein a carbon of the 6 membered ring heterocyclic group may optionally form a carbonyl,
• (iv) —CH2—R5, —CHMe-R5
• wherein R5 is a 6 membered ring heterocyclic group optionally substituted with 1 to 3 substituents independently selected from:
• (a) F, C1-6 alkyl, —C1-6 alkyl-CF3, CF3, CHF2, CH2F, 3 to 8 membered ring cycloalkyl, —C1-6 alkyl-C1-6 alkoxy, —C1-6 alkyl-C3-8 cycloalkyl, SO2 linked to a 4 to 8 membered ring heterocyclic group, C1-6 alkyl substituted with a 4 to 8 membered ring heterocyclic, —COCF3, —C(O)S—C1-6 alkyl, SO2NRxRy, CONRxRy, CO2C1-6 alkyl,
• (b) —SO2C1-6 alkyl optionally substituted with C1-6 alkoxy or CN,
• (c) COC1-6 alkyl optionally substituted with C1-6 alkoxy or —S—C1-6 alkyl, and
• (v) —CO—R6
• wherein R6 is a 6 membered ring heterocyclic group optionally substituted with 1 to 3 substituents independently selected from:
• (a) F, C1-6 alkyl, —C1-6 alkyl-CF3, CF3, CHF2, CH2F, 3 to 8 membered ring cycloalkyl, —C1-6 alkyl-C1-6 alkoxy, —C1-6 alkyl-C3-8 cycloalkyl, SO2 linked to a 4 to 8 membered ring heterocyclic group, C1-6 alkyl substituted with a 4 to 8 membered ring heterocyclic, —COCF3, —C(O)S—C1-6 alkyl, SO2NRxRy, CONRxRy,
• (b) —SO2C1-6 alkyl optionally substituted with C1-6 alkoxy or CN,
• Ra is selected from the group consisting of C1-6 alkyl, a 4 to 8 membered ring heterocyclic group, a 3 to 8 membered ring cycloalkyl group, and an aryl group,
• wherein the 4 to 8 membered ring heterocyclic group and the 3 to 8 membered ring cycloalkyl group are optionally substituted with 1 to 3 substituents independently selected from C1-6 alkyl, —CO—C1-6 alkyl, —CO—C1-6 alkyl-S—C1-6 alkyl, and —CO—C1-6 alkyl-O—C1-6 alkyl,
• wherein the C1-6 alkyl is optionally substituted with OH, NRxRy, 1 to 3 F, an aryl group, a 4 to 8 membered ring heterocyclic group, a 3 to 8 membered ring cycloalkyl group, or C1-6 alkoxy optionally substituted with 1 to 3 F,
• Rx and Ry are each independently selected from H, and C1-6 alkyl, or Rx and Ry are joined to form a 4 to 7 membered ring heterocyclic ring;
• Rb is a 4 to 8 membered ring heterocyclic group optionally substituted with 1 to 3 substituents independently selected from C1-6 alkyl, and CO—C1-6 alkyl;
• Rc is a 4 to 8 membered ring heterocyclic group optionally substituted with 1 to 3 substituents independently selected from C1-6 alkyl, and CO—C1-6 alkyl;
• R2 is selected from the group consisting of:
• which are optionally substituted with 1 to 3 Rk,
• each Rk is independently C1-4 alkyl, wherein the C1-4 alkyl is optionally substituted with NRuRv, OH, O—C1-4 alkyl, CN, or 1 to 3 F, wherein two Rk substituents on the same carbon may optionally form a spiro C3-5 cycloalkyl;
• Ru and Rv are each independently selected from H and C1-4 alkyl;
• R is selected from the group consisting of:
• wherein Rs and Rt are each independently selected from the group consisting of H, C3-5 cycloalkyl and C1-6 alkyl, wherein the C1-6 alkyl group may be optionally substituted with 1 to 3 substituents independently selected from the group consisting of C1-3 alkoxy and —S—C1-3 alkyl,
• or Rs and Rt form a 4 to 6 membered monocyclic heterocyclic group optionally substituted with 1 to 3 substituents independently selected from the group consisting of C1-6 alkyl, C1-3 alkoxy, —S—C1-3 alkyl and —C1-3 alkyl-C1-3 alkoxy;
• and
• R3 and R4 are each independently selected from C1-4 alkyl and H.