Processes for making epothilone compounds and analogs

A process for making a compound having the formula G,

• or a pharmaceutically-acceptable salt thereof, wherein
• R1 is hydrogen or forms a bond with Z1;
• Z1 is hydroxyl, cyano, is taken together with R1 to form a bond, or is ORp;
• Z2 is hydroxyl or ORp;
• wherein each Rp is a protecting group;
• R2, R3, and R5 are independently, hydrogen, alkyl, substituted alkyl, aryl or substituted aryl;
• or R2 and R3 may be taken together with the carbon to which they are attached to form an optionally-substituted cycloalkyl;
• R4 is hydrogen, alkyl, substituted alkyl, alkenyl, alkynyl, aryl, or substituted aryl;
• R6 is hydrogen, alkyl or substituted alkyl;
• R12 is H, alkyl, substituted alkyl, or halogen;
• and
• R13 is aryl, substituted aryl, heteroaryl or substituted heteroaryl;
• which comprises
• (i) preparing an epi-epothilone intermediate compound having the formula (A.1),
• by reacting a compound having the formula (C),
• wherein R1, R2, R3, R4, R5, R6, R12, R13, Z1 and Z2 are as described above, with at least one halogenating agent to provide compounds having the formula (B.1) and/or (B.2), wherein Y is halogen and R1, R2, R3, R4, R5, R6, R12, R13, Z1 and Z2 are as described above
• followed by treatment of compounds (B.1) and/or (B.2) with base to provide the compound of formula A.1;
• (ii) treating the epi-epothilone intermediate of formula (A.1) with an azide donor in an alcohol solvent to provide azido-alcohols of formula (E.1) and (E.2),
• and
• (iii) treating the intermediate compounds provided by step (ii) with an azide reducing agent in a polar solvent to provide the compounds of formula (G).