Process and intermediates for the preparation of abiraterone acetate

A process for the preparation of (3β)17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate represented by the structure of formula (1), and salts thereof

• the process comprising the steps of:
• a) coupling a protected dehydroepiandrosterone (10) with a pyridinyl derivative (11) to form a pyridinyl hydroxy derivative (12):
• wherein
• PG is a hydroxyl protecting group;
• and
• M is selected from the group consisting of Li, Na, K, MgX, ZnX, CdX, Si(R)3, Ge(R)3 and Sn(R3);
• wherein X is a halogen and R is a substituted or unsubstituted alkyl, cycloalkyl, alkylaryl or aryl;
• b) converting compound (12) to (17-pyridin-3-yl)-androsta-5,16-diene (13):
• and
• c) transforming compound (13) into (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-ol (Abiraterone acetate) (1).

A process for preparing a compound represented by the structure of formula (A), comprising the step of coupling a ketone or an aldehyde represented by the structure of formula (C) with a compound of formula (11) to a form pyridinyl-tertiary alcohol (A)

• wherein
• R1 and R2 are each H or an unsubstituted or substituted alkyl, cycloalkyl, alkylaryl or aryl;
• and
• M is selected from the group consisting of Li, Na, K, MgX, ZnX, CdX, Si(R)3, Ge(R)3 and Sn(R)3;
• wherein X is a halogen and R is a substituted or unsubstituted alkyl, cycloalkyl, alkylaryl or aryl.

A compound represented by the structure of formula (14):

• wherein
• PG is a hydroxyl protecting group;
• and
• LG is a leaving group selected from a halogen or a sulfonate ester group of the formula —OSO2Rb wherein Rb is a substituted or unsubstituted alkyl, cycloalkyl, alkylaryl or aryl.