反应详情

温度

60 °C

Ethanol (2 mL) and acetone (15 mL) were added to amorphous ((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 diHCl (1102 mg, Example 4). The reaction mixture was warmed to 60° C. and sonicated for 1 min to give a hazy solution. Ethanol (2 mL) was added to provide a clear solution, which was heated at 60° C. After about 5 mL of solvent had evaporated, acetone (10 mL) was added until the solution turned cloudy. The contents were stirred overnight to provide a crystalline slurry which was stirred for an additional 48 h and then allowed to settle. The supernatant solvents were decanted. To the remaining solid suspension was added water (0.5 mL) and dioxane (2 mL). The resulting mixture was filtered to give a white to off-white solid which was dried under vacuum for 12 h to provide the title compound (628 mg).

1. customsonicated for 1 min
2. customto give a hazy solution
3. customto provide a clear solution, which
4. temperaturewas heated at 60° C
5. customAfter about 5 mL of solvent had evaporated
6. additionacetone (10 mL) was added until the solution
7. customto provide a crystalline slurry which
8. stirringwas stirred for an additional 48 h
9. customThe supernatant solvents were decanted
10. additionTo the remaining solid suspension was added water (0.5 mL) and dioxane (2 mL)
11. filtrationThe resulting mixture was filtered
12. customto give a white to off-white solid which
13. customwas dried under vacuum for 12 h