Pyridinyl and fused pyridinyl triazolone derivatives

A method for inhibiting BTK in a subject, the method comprising administering to the subject a compound of Formula 1,

• a tautomer thereof or a pharmaceutically acceptable salt of the compound or tautomer, wherein:
• R1 is selected from hydrogen, halo, and C1-4 alkyl;
• R2 and R3 are each independently selected from hydrogen, halo, and C1-6 alkyl, or R2 and R3, together with carbon atoms to which they are attached, form a benzene ring or a pyridine ring in which the benzene ring is optionally substituted with from one to four substituents independently selected from halo, —CN, —OR8, and C1-6 alkyl, and the pyridine ring is optionally substituted with from one to three substituents independently selected from halo, —CN, —OR8, and C1-6 alkyl;
• R4 has the formula
• in which indicates a point of attachment;
• L is selected from —O—, —CH2O—, and —N(R4e)—;
• R4a is selected from —CH2R5 and ethenyl optionally substituted with from one to three substituents independently selected from halo, cyano, and C1-6 alkyl optionally substituted with —N(R11)R12;
• and
• (a) R4c is hydrogen, R4e is selected from hydrogen and C1-4 alkyl when L is —N(R4e)—, and R4b and R4d, together with a nitrogen atom and carbon atoms to which R4b, R4c, and R4d are respectively attached, form a pyrrolidine ring or a piperidine ring, each ring optionally substituted with from one to six substituents independently selected from halo, C1-4 alkyl, and C1-4 haloalkyl;
• or
• (b) R4b is selected from hydrogen and C1-4 alkyl, R4d is hydrogen, L is —N(R4e)—, and R4c and R4e, together with the carbon atoms and a nitrogen atom to which R4c, R4d, and R4e are respectively attached, form a pyrrolidine ring or a piperidine ring, each ring optionally substituted with from one to six substituents independently selected from halo, C1-4 alkyl, and C1-4 haloalkyl;
• or
• (c) R4d is hydrogen, R4e, is selected from hydrogen and C1-4 alkyl when L is —N(R4e)—, and R4b and R4c, together with the nitrogen and carbon atoms to which R4b and R4c are respectively attached, form pyrrolidine ring or a piperidine ring, each ring optionally substituted with from one to six substituents independently selected from halo, C1-4 alkyl, and C1-4 haloalkyl;
• R5 is selected from hydrogen, halo, and C1-4 alkyl;
• each R8 is independently selected from hydrogen and C1-6 alkyl;
• and
• each R11 and R12 is independently selected from hydrogen and
• C1-6 alkyl.