Pyrrolopyridazine jak3 inhibitors and their use for the treatment of inflammatory and autoimmune diseases

A compound of Formula (II):

• or stereoisomers or salts thereof, wherein:
• R1 is C1-6 alkyl substituted with zero to 3 substituent groups independently selected from F, —OH, —CF3, —NH2, —C(O)OH, —C(O)OCH3, —C(O)NH2, —C(O)NHCH2CN, —C(O)NH(phenyl), —NHC(O)CH2CN, —NHS(O)2CH3, —OP(O)(OH)2, phenyl, fluorophenyl, oxazolyl substituted with —C(O)NH2;
• and/or two substituent groups along with the carbon atom to which they are attached, form a cyclopropyl ring;
• R2 is -L-Rx or Ry;
• L is —NHC(O)—, —NHC(O)O—, —NHS(O)2—, —NHC(O)NH—, —NHC(O)O—, or —C(O)NH—;
• Rx is C1-6 alkyl, C3-6 cycloalkyl, C1-4 fluoroalkyl, and a cyclic group selected from 5-membered heterocyclyl having at least one oxygen heteroatom, 5-membered heteroaryl having at least one nitrogen heteroatom, or phenyl, each cyclic group substituted with zero to 2 substituents independently selected from F, Cl, —OH, —CN, C1-3 alkyl, C1-3 alkoxy, —C(O)OH, and/or —NH2;
• and
• Ry is:
• a) phenyl substituted with zero to 2 substituents independently selected from
• i) F, Cl, —CN, C1-4 alkyl, —O(C1-3 alkyl), —C(O)OH, —NH2, —NH(C1-3 alkyl), —N(C1-3 alkyl)2, C3-6 cycloalkyl, and/or C2-4 alkenyl;
• ii) C1-4 alkyl substituted with —CN, —OH, —NH2, —NH(CH3), —N(CH3)2, C3-6 cycloalkyl, morpholinyl, piperidinyl substituted with methoxyphenyl, —NHC(O)Rm, —NHC(O)NHRn, —NHCH(═N—CN)NH(C1-3 alkyl), and/or —NHS(O)2(C1-3 alkyl);
• wherein Rm is C1-4 alkyl, C3-6 cycloalkyl, hydroxy(C3-6 cycloalkyl), C1-3 cyanoalkyl, C1-4 hydroxyalkyl, —CH2NH2, —CH2H(CH3), —CH2N(CH3)2, phenyl, phenyl-S(O)2NH2, phenyl-NHC(O)CH3, pyrrolidinyl, furanyl, pyridinyl, —CH2OC(O)(C1-3 alkyl), —CH2(morpholinyl), or CH2NHS(O)2(methylphenyl);
• and Rn is H, C1-3 alkyl, C3-6 cycloalkyl, or C1-4 hydroxyalkyl;
• iii) —C(O)NRiRj wherein Ri is H or —CH3, and R is C1-3 alkyl, C3-6 cycloalkyl, —CH2C(O)NH2, —CH2C(O)NH(CH3), —CH2C(O)N(CH3)2, or —CH2CH2N(CH3)2;
• iv) —OC(O)(C1-3 alkyl) and/or —C(O)(N-methyl morpholinyl);
• v) —NHC(O)Rk wherein Rk is H, C1-3 alkyl, or C3-6 cycloalkyl;
• vi) —S(O)2(C1-3 alkyl), —NHS(O)2(C1-3 alkyl), —S(O)2NH2, and/or —S(O)2N(CH3)2;
• vii) thiophenyl, morpholinonyl, imidazolyl, oxazolyl, and/or imidazolidine-2,4-dionyl, each substituted with zero to 1 substituent selected from —CH3, —C(O)O(C1-3 alkyl), and dimethylaminophenyl;
• b) heterocycle selected from azetidinonyl, pyrrolidinonyl, morpholinonyl, pyridinonyl, imidazolidinonyl, oxazolidinonyl, propane-1,3-sultam, butane-1,4-sultam, 5-thioxo-4,5-dihydro-1,3,4-oxadiazoly-2-yl, and 5-methylthio-1,3,4-oxadiazoly-2-yl, wherein said heterocycle is substituted with zero to 1 substituent selected from C1-4 alkyl, C1-3 fluoroalkyl, —NHC(O)O(C1-4 alkyl), and phenyl;
• or
• c) heteroaryl selected from pyrrolyl, pyrazolyl, thiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, quinolinyl, 3,4-dihydroisoquinolin-1(2H)-onyl, benzo[d][1,3]dioxolyl, quinolin-2(1H)-onyl, benzothiazolyl, 1H-benzo[d]imidazol-2(3H)-onyl, wherein said heteroaryl is substituted with zero to 3 substituents independently selected from F, Cl, —OH, —CN, C1-4 alkyl, C1-3 fluoroalkyl, —O(C1-4 alkyl), —NH2, —NH(C1-3 alkyl), —N(C1-3 alkyl)2, —C(O)NH2, —C(O)NH(C1-3 alkyl), —C(O)N(C1-3 alkyl)2, —S(O)2(C1-3 alkyl), —NHCH2CH2N(C1-2 alkyl)2, —N(CH3)CH2CH2N(C1-2 alkyl)2, —NHCH2CH2(morpholinyl), piperidinyl, piperazinyl, phenyl, chlorophenyl, methoxyphenyl, dimethylaminophenyl, pyridinyl, morpholinyl, N-methyl piperazinyl, and/or piperazinyl(C(O)O(t-butyl)).