Processes and intermediates for preparing anti-cancer compounds

A method of preparing a compound of formula 6 or 7

• or a pharmaceutically acceptable salt or solvate thereof, wherein R6 is C1-C10 alkyl or —(CH2)mO(CH2)nCH3;
• R7 is C1-C10 alkyl or —(C1-C6 alkyl)(C6-C10 aryl) wherein the foregoing R7 groups are optionally substituted by 1 to 3 substituents independently selected from halo, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6 alkyl)sulfonyl, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryloxy and C6-C10arylsulfonyl;
• each m is independently an integer from 1 to 6, and n is an integer from 0 to 3;
• R15 is H, C1-C10 alkyl, or —(CH2)q(C6-C10 aryl), wherein q is an integer from 0 to 4;
• which comprises treating a compound of the formula 8
• wherein R6 and R15 are as defined above,
• G1 is —C(OH)R3R4, and R3 and R4 are each independently C1-C6 alkyl;
• with a primary or secondary alcohol of the formula R7—OH wherein R7 is C1-C10 alkyl or —(C1-C6 alkyl)(C6-C10 aryl) and the foregoing R7 groups are optionally substituted by 1 to 3 substituents independently selected from halo, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6 alkyl)sulfonyl, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryloxy and C6-C10 arylsulfonyl;
• in the presence of an alkali-metal or alkaline-metal hydroxide.

A method of preparing a compound of the formula 9

• or a pharmaceutically acceptable salt or solvate thereof,
• wherein R6 is C1-C10 alkyl or —(CH2)mO(CH2)nCH3;
• R7 is C1-C10 alkyl or —(C1-C6 alkyl)(C6-C10 aryl) wherein the foregoing R7 groups are optionally substituted by 1 to 3 substituents independently selected from halo, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6 alkyl)sulfonyl, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryloxy and C6-C10arylsulfonyl;
• each m is independently an integer from 1 to 6, and n is an integer from 0 to 3;
• R8, R9 and R10 are each independently selected from H, C1-C10 alkyl, halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —OR11, —C(O)R11, —C(O)OR11, —NR12C(O)OR14, —OC(O)R11, —NR12SO2R14, —SO2NR11R12, —NR12C(O)R11, —C(O)NR11R12, —NR11R12, —S(O)j(CH2)q(C6-C10 aryl), —S(O)j(C1-C6 alkyl), wherein j is an integer from 0 to 2, —(CH2)q(C6-C10 aryl), —O(CH2)q(C6-C10 aryl), —NR12(CH2)q(C6-C10 aryl), and —(CH2)q(4-10 membered heterocyclic), wherein q is an integer from 0 to 4;
• said alkyl group optionally contains 1 or 2 hetero moieties selected from O, —S(O)j— wherein j is an integer from 0 to 2, and —N(R12)— with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other;
• said aryl and heterocyclic groups are optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4-10 membered heterocyclic group;
• and said alkyl, aryl and heterocyclic groups are optionally substituted by 1 to 5 substituents independently selected from halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR12SO2R14, —SO2NR11R12, —C(O)R11, —C(O)OR11, —OC(O)R11, —NR12C(O)OR14, —NR12C(O)R11, —C(O)NR11R12, —NR11R12, —OR11, C1-C10 alkyl, —(CH2)q(C6-C10 aryl), and —(CH2)q(4-10 membered heterocyclic), wherein q is an integer ranging from 0 to 4;
• each R11 is independently selected from H, C1-C10 alkyl, —(CH2)q(C6-C10 aryl), and —(CH2)q(4-10 membered heterocyclic), wherein q is an integer ranging from 0 to 4;
• said alkyl group optionally includes 1 or 2 hetero moieties selected from O, —S(O)j— wherein j is an integer from 0 to 2, and —N(R12)— with the proviso that two O atoms, two S atoms, or an O and S atom are not attached directly to each other;
• said aryl and heterocyclic R11 groups are optionally fused to a C6-C10 aryl group, a C5-C8 saturated cyclic group, or a 4-10 membered heterocyclic group;
• and the foregoing R11 substituents, except H, are optionally substituted by 1 to 5 substituents independently selected from halo, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —C(O)R12, —C(O)OR12, —OC(O)R12, —NR12C(O)R13, —C(O)NR12R13, —NR12R13, hydroxy, C1-C6 alkyl, and C1-C6 alkoxy;
• each R12 and R13 is independently H or C1-C6 alkyl;
• R14 is selected from the substituents provided in the definition of R11 except H;
• R15 is H, C1-C10 alkyl, or —(CH2)q(C6-C10 aryl), wherein q is an integer from 0 to 4;
• which comprises treating a compound of the formula 10
• wherein R15, R6, R8, R9 and R10 are as defined above;
• with a primary or secondary alcohol of the formula R7—OH wherein R7 is C1-C10 alkyl or —(C1-C6 alkyl)(C6-C10 aryl) and the foregoing R7 groups are optionally substituted by 1 to 3 substituents independently selected from halo, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6 alkyl)sulfonyl, C1-C6 alkyl, C1-C6 alkoxy, C6-C10 aryloxy and C6-C10arylsulfonyl;
• in the presence of an alkali-metal or alkaline-metal hydroxide.

A compound of formula 2

• wherein R1 and R2 are each independently selected from C1-C10 alkyl and C1-C10 alkoxy wherein said alkyl and alkoxy are optionally substituted by up to 2 substituents independently selected from hydroxy and C1-C6 alkoxy;
• G is a blocking group selected from —C(OH)R3R4 and —SiR3R4R5;
• R3, R4 and R5 are each independently C1-C6 alkyl;
• and,
• R15 is H, C1-C10 alkyl, or —(CH2)q(C6-C10 aryl), wherein q is an integer from 0 to 4.