Crystalline form of a pyridyl-piperazinyl hepatitis c virus inhibitor

A process for preparing crystalline ((S)-1-{(S)-2-[4-(4′-{[6-((2R,5S)-2,5-dimethyl-4-methylcarbamoyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-2′-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (compound 1), the process comprising:

• (a) dissolving the crude product of the reaction of ((S)-1-{(S)-2-[4-(4′-{[6-((2R,5S)-2,5-dimethyl-piperazin-1-yl)-pyridine-3-carbonyl}-amino]-2′-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester with methylaminoformyl chloride in methanol,
• (b) adding water and seeds of crystalline compound 1, such that the ratio of methanol to water is between about 2.5:1 and about 2.7:1 to form a reaction mixture;
• and
• (c) stirring the reaction mixture until crystalline compound 1 is formed.

A process for preparing the crystalline dihydrochloride salt of ((S)-1-{(S)-2-[4-(4′-{[6-((2R,5S)-2,5-dimethyl-4-methylcarbamoyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-2′-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (compound 1) monohydrate form, the process comprising:

• (a) dissolving amorphous dihydrochloride salt of compound 1 in ethanol, or an ethanol, water and acetone mixture with heating to form a solution;
• (b) stirring the solution until a thick slurry is formed;
• and
• (c) isolating the crystalline dihydrochloride salt of compound 1 monohydrate form from the thick slurry.