Process for the preparation of enzalutamide

1. An improved process for the preparation of enzalutamide of Formula I,

comprising:

i) reacting 4-amino-2-trifluoromethyl benzonitrile of Formula 2 with thiocarbonyldiimidazole (TCDI) in a solvent in the presence of a base to obtain a compound of Formula 3,

ii) converting the compound of Formula 3 to enzalutamide.

2. The process of claim 1 , wherein the solvent in step i) is selected from one of a halogenated hydrocarbon, an ether, an amide, a nitrile, and mixtures thereof.

3. The process of claim 1 , wherein the solvent is selected from one of methylene chloride, tetrahydrofuran, dimethyl formamide, and mixtures thereof.

4. The process of claim 1 , wherein the base in step i) is selected from one of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, lithium carbonate, sodium bicarbonate, potassium bicarbonate, ammonia, triethylamine, N,N-diisopropyl ethyl amine, and mixtures thereof.

5. The process of claim 1 , wherein the suitable base is triethyl amine.

6. The process of claim 1 , further comprising:

a) prior to the step ii) converting the compound of Formula 3 to enzalutamide, dissolving the 4-isothiocyanato-2-(trifluoromethyl) benzonitrile of Formula 3 in a solvent at a suitable temperature;

b) filtering the step a) solution;

c) optionally concentrating the filtrate;

d) cooling the filtrate to less than 10° C.; and

e) isolating the purified compound of Formula 3.

7. The process of claim 6 , wherein the solvent in step a) is selected from one of a hydrocarbon solvent, an ether; and mixtures thereof,

wherein the hydrocarbon solvent is one of hexane, cyclohexane, heptane, pentane, cyclopentane, and methyl cyclohexane, and

wherein the ether is one of diethyl ether, and 1,4-dioxane.

8. The process of claim 7 , wherein the solvent is hexane.

9. The process of claim 6 , wherein the step a) is carried out at a temperature of about 50° C. to 70° C.

10. The process of claim 6 , wherein the step b) filtration is carried out at a temperature of about 50° C. to 70° C.

11. The process of claim 6 , wherein the isolated compound of Formula 3 contains less than 0.2% as measured by HPLC of any one or more of Formula 3A, Formula 3B, and Formula 3C:

12. The process of claim 1 , where the enzalutamide contains less than 0.05% as measured by HPLC of any one or more of the following compounds:

13. The process of claim 1 , further comprising:

iii) forming a pharmaceutical composition comprising the enzalutamide and at least one pharmaceutically acceptable excipient.