Thiolactams and uses thereof

A process for preparing a compound of formula I:

• or a salt thereof, wherein
• R1 is selected from hydrogen, —CN, halogen, optionally substituted C1-6aliphatic, or —YR1a,
• wherein Y is —O—, —S—, or —NR1a, and each occurrence of R1a is independently hydrogen, or optionally substituted C1-6aliphatic;
• R2 is selected from hydrogen, halogen, —ZR2a, or —OR2b,
• wherein Z is an optionally substituted C1-6 alkylene chain, and R2a is —OR2b, —N(R2b)2, —SR2b, —C(O)N(R2b)2, —N(R2b)C(O)R2b, —SO2N(R2b)2, —NR2bSO2R2b, —NR2bC(O)N(R2b)2, or —NR2bSO2N(R2b)2, wherein each occurrence of R2b is independently hydrogen or optionally substituted C1-6alkyl, or two occurrences of R2b, taken together with a nitrogen atom to which they are bound, form an optionally substituted 3-7-membered heterocyclyl ring;
• R3 is selected from hydrogen, halogen, optionally substituted C1-4alkyl, or optionally substituted C1-4alkoxy;
• R4 is selected from hydrogen, optionally substituted C1-6aliphatic, an optionally substituted 3-7-membered heterocyclyl ring, —(CH2)xNR4aR4b, —(CH2)xNR4aC(O)R4b, —(CH2)xNR4aS(O)2R4b, —(CH2)xC(O)R4b, —(CH2)xC(O)NR4aR4b, —(CH2)xS(O)2NR4aR4b, or —(CH2)xOR4b,
• wherein
• each occurrence of x is independently 0-6;
• wherein R4a is hydrogen or optionally substituted C1-6aliphatic, and
• R4b is hydrogen, optionally substituted C1-6aliphatic, optionally substituted C3-7-heterocyclyl or C3-7carbocyclyl ring, or is W—R4c, wherein W is an optionally substituted C2-6 alkylene chain, and R4c is an optionally substituted C3-7-heterocyclyl ring, —OR4d, —N(R4d)2, —SR4d, —C(O)N(R4d)2, —N(R4d)C(O)R4d, —SO2N(R4d)2, —NR4dSO2R4d, —NR4dC(O)N(R4d)2, or —NR4dSO2N(R4d)2, wherein each occurrence of R4d is independently hydrogen or optionally substituted C1-6aliphatic, or two occurrences of R4d, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-7-membered heterocyclyl ring;
• or wherein R4a and R4b, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-7-membered heterocyclyl ring;
• R5 is hydrogen, optionally substituted C1-6aliphatic, an optionally substituted C3-7-heterocyclyl ring, or is X—R5a, wherein X is an optionally substituted C2-6 alkylene chain or —NR5c,
• wherein when X is an optionally substituted C2-6 alkylene chain R5a is —OR5b, —N(R5b)2, —SR5b, —C(O)N(R5b)2, —N(R5b)C(O)R5b, —SO2N(R5b)2, —NR5bSO2R5b, —NR5bC(O)N(R5b)2, or —NR5bSO2N(R5b)2;
• and
• when X is —NR5c, R5a is hydrogen or optionally substituted C1-6aliphatic, or R5a and R5c, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-7-membered heterocyclyl ring;
• wherein each occurrence of R5b and R5c is independently hydrogen or optionally substituted C1-6aliphatic, or two occurrences of R5b, or R5a and R5c, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-7-membered heterocyclyl ring;
• or
• wherein R4 and R5, taken together, form an optionally substituted 5-7-membered cycloaliphatic or heterocyclyl ring;
• and
• R6 is selected from hydrogen, halogen, optionally substituted C1-4alkyl, or optionally substituted C1-4alkoxy, the process comprising the steps of:
• (a-1) treating a compound of formula II:
• wherein variables R1 and R2 are as described above, with a compound of formula III:
• wherein variables R3, R4, R5 and R6 are as described above;
• to form a compound of formula IV:
• wherein variables R1, R2, R3, R4, R5 and R6 are as described above;
• and
• (a-2) thionating the compound of formula IV to form the compound of formula I.