Process for preparation of androgen receptor antagonist

Patent metadata

Field	Value
Publication number	US-9611225-B2
Application number	US-201514606390-A
Country	US
Kind code	B2
Filing date	Jan 27, 2015
Priority date	Jan 27, 2014
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

The present invention provides an isopropanol solvate of enzalutamide. The present invention also provides a process for the preparation of androgen receptor antagonist. In particular, the present invention provides a process for the preparation of enzalutamide or its pharmaceutically acceptable salts, hydrates, solvates, polymorphs or intermediates thereof.

First claim

We claim:

1. A process for the preparation of enzalutamide of Formula (I)

the process comprising:
reacting a compound of Formula (VI)

with a compound of Formula (V)

wherein L is Cl, Br, I or a leaving group,
to obtain a compound of Formula (IV)

optionally, purifying the compound of Formula (IV);
reacting the compound of Formula (IV) with a compound of Formula (II)

to obtain the enzalutamide of Formula (I); and
optionally, purifying the enzalutamide of Formula (I) in one or more of solvents.

2. The process according to claim 1 , wherein the compound of Formula (IV) is reacted with the compound of Formula (II) in presence of a base in one or more solvents.

3. The process according to claim 2 , wherein the base comprises of inorganic base or organic base wherein the inorganic base comprises one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide; sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate; and ammonia or its aqueous solution; or the organic base comprises one or more of methyl amine, ethyl amine, TEA, TBA, DIPA, DIPEA, pyridine, piperidine, morpholine, DBU, DABCO and DBN.

4. The process according to claim 2 , wherein the solvent comprises one or more of esters selected from ethyl acetate, isopropyl acetate, t-butyl acetate, and isobutyl acetate; hydrocarbons selected from toluene, xylene, ethyl benzene, heptane, hexane, and cyclohexane; and chlorinated solvents selected from methylene dichloride, ethylene dichloride, chlorobenzene, chloroform, and carbon tetrachloride.

5. The process according to claim 1 , wherein the purification of compound (IV) is performed in one or more solvents comprises of alcohols selected from methanol, ethanol, isopropanol, butanol, t-butanol, and isoamylalcohol; ketones selected from acetone, methyl isobutyl ketone, and methyl ethyl ketone; esters selected from ethyl acetate, isopropyl acetate; t-butyl acetate, and isobutyl acetate; and chlorinated solvents selected from methylene dichloride, ethylene dichloride, and chlorobenzene.

6. The process according to claim 1 , wherein enzalutamide of Formula (I) is obtained in crystalline Form-A characterized by x-ray powder diffraction (XRD) having characteristic peaks expressed in degrees 2θ (±0.2° 2θ) at about 13.1°, 13.4°, 14.3°, 16.6°, 21.1°, 22.7° and 24.4°±0.2° 2θ and/or by differential scanning calorimetry (DSC) having onset at about 197±5° C. and an endothermic peak at about 198±5° C.

Assignees

• Cadila Healthcare Ltd

Inventors

• Dwivedi Shri Prakash Dhar
• Singh Kumar Kamlesh
• Charan Ganpat Dan Shimbhu

Classifications

• C07D233/86 Primary

  Oxygen and sulfur atoms, e.g. thiohydantoin · CPC title

• C07C231/12

  by reactions not involving the formation of carboxamide groups · CPC title

• C07C237/30

  having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms · CPC title