PROCESS FOR THE PREPARATION OF A DIARYLTHIOHYDANTOIN COMPOUND

摘要

Disclosed are processes and intermediates for the preparation of compound (X), which is currently being investigated for the treatment of prostate cancer.;

主权项

1. A process for the preparation of compound (X)comprising reacting a compound of formula (XI-c), wherein P is an amino protecting group, with compound (IV) under amide-bond formation conditions; in the presence of an amide coupling reagent; and in the presence of a catalyst; in an organic solvent; at a temperature in the range of from about 0° C. to about 50° C.; to yield the corresponding compound of formula (XII-c); or, reacting compound (IV) with phosgene or a phosgene analog; in the presence of an organic base; in an aprotic solvent; then treating a resulting isocyanate intermediate (IVa), optionally without isolation, with a compound of formula (XI-c); in the presence of a non-nucleophilic base; at a temperature in the range of from about −20° C. to about 80° C.; to yield the corresponding compound of formula (XII-c); reacting a compound of formula (XII-c) under amino deprotection conditions; in an organic solvent; at a temperature greater than ambient temperature; to yield the corresponding compound (XIII); reacting compound (XIII) with a compound of formula (2c-1) wherein X is chloro, bromo, or iodo, and W is C1-8alkoxy or methylamino; in the presence of a copper (0) source or a copper salt; in the presence of an inorganic base; in an organic solvent; optionally in the presence of a ligand; optionally in the presence of a reducing agent; at a temperature in the range of from about room temperature to about 140° C.; to yield the corresponding compound of formula (2c-2) wherein W is C1-8alkoxy (2c-2B) or methylamino (XVII); converting a compound of formula (2c-2) to compound (X).