Macrocyclic hepatitis C serine protease inhibitors

A method of producing a compound of formula I, or a pharmaceutically acceptable salt, ester or prodrug thereof, comprising the step of reacting a compound of formula II:

• wherein,
• J is absent, optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, —C(O)—, —O—C(O)—, —N(R3)—C(O)—, —C(S)—, —C(═NR4)—, —S(O)—, —S(O2)—, or —N(R3)—;
• A is optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• optionally substituted aryl, optionally substituted arylalkyl, optionally substituted alkoxy, optionally substituted heteroaryl, optionally substituted heterocyclic, or optionally substituted carbocyclic;
• G is -E-R5;
• wherein E is absent;
• optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• or —O—, —S—, —N(R3)—, —N(R3)S(Op)—, —N(R3)C(O)—, —N(R3)C(O)S(Op)—, —OS(Op)—, —C(O)S(Op)—, or —C(O)N(R3)S(Op)—;
• p is 0, 1, or 2;
• R5 is H;
• optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• optionally substituted carbocyclic, optionally substituted heterocyclic, optionally substituted aryl, or optionally substituted heteroaryl;
• Each R3 is independently selected at each occurrence from the following:
• optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• optionally substituted aryl;
• optionally substituted heteroaryl;
• optionally substituted heterocyclic;
• optionally substituted carbocyclic;
• or hydrogen;
• L is absent or is selected from optionally substituted alkylene, optionally substituted alkenylene or optionally substituted alkynylene, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• j=0, 1, 2, 3, or 4;
• k=0, 1, 2, or 3;
• m=0, 1, or 2;
• and
• denotes a carbon-carbon single or double bond;
• and
• LG is a leaving group;
• with a compound of formula III:
• wherein:
• Each R1 is independently selected from
• (i) halogen, hydroxy, amino, —CN, —CF3, —N3, —NO2, —OR4, —SR4, —SOR4, —SO2R4, —N(R3)S(O)2—R4, —N(R3)S(O2)NR3R4, —NR3R4, —C(O)OR4, —C(O)R4, —C(O)NR3R4, or —N(R3)C(O)R4;
• (ii) optionally substituted aryl;
• (iii) optionally substituted heteroaryl;
• (iv) optionally substituted heterocyclic;
• (v) optionally substituted carbocyclic;
• or
• (vi) optionally substituted alkyl, optionally substituted alkenyl, or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• R3 and R4 are each independently selected at each occurrence from the following:
• optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, each containing 0, 1, 2, or 3 heteroatoms selected from O, S, or N;
• optionally substituted aryl;
• optionally substituted heteroaryl;
• optionally substituted heterocyclic;
• optionally substituted carbocyclic;
• or hydrogen;
• n is 0, 1, 2, 3, or 4;
• Y is N or CR″;
• wherein A, R1, R′ and/or R″ can be taken together to form a ring;
• wherein if Y is N, then R′ is optionally substituted heterocyclic or optionally substituted carbocyclic, and comprises two or more fused rings, and wherein R′ is not
• or
• wherein if Y is —C(R″)—, then R′ and R″ taken together with the carbon atoms to which they are attached form an aryl or heteroaryl ring, each said ring is optionally substituted;
• provided that said compound is not tert-butyl (2R,6S,13aS,14aR,16aS,Z)-2-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)-14a-(cyclopropylsulfonylcarbamoyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-ylcarbamate;
• to thereby produce a compound of formula I.