反应详情

To a solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]methyl]piperazine (152 mg) in ethyl acetate (2 ml) was added triethylamine (0.048 ml) and methanesulfonyl chloride (0.027 ml) at room temperature. After stirring for 10 minutes, the mixture was quenched with water and extracted with ethyl acetate. The combined extracts were washed with water and brine successively, dried over magnesium sulfate, and evaporated under reduced pressure. The obtained residue was dissolved with N,N-dimethylformamide (2 ml) and added morpholine (0.028 ml), potassium carbonate (74 mg) and potassium iodide (13 mg). After stirring at 70° C. for 6 hours, the mixture was quenched with water and extracted with ethyl acetate. The combined extracts were washed with water and brine successively, dried over magnesium sulfate, and evaporated under reduced pressure. The obtained residue was dissolved in ethyl acetate and treated with 4N hydrogen chloride in ethyl acetate (0.2 ml) at room temperature. The mixture was added hexane, filtered, and dried over reduced pressure to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-morpholinoethyl)-1H-pyrazol-4-yl]methyl]piperazine dihydrochloride (188.7 mg) as a solid.

1. customthe mixture was quenched with water
2. extractionextracted with ethyl acetate
3. washThe combined extracts were washed with water and brine successively
4. dry with materialdried over magnesium sulfate
5. customevaporated under reduced pressure
6. dissolutionThe obtained residue was dissolved with N,N-dimethylformamide (2 ml)
7. additionadded morpholine (0.028 ml), potassium carbonate (74 mg) and potassium iodide (13 mg)
8. stirringAfter stirring at 70° C. for 6 hours
9. customthe mixture was quenched with water
10. extractionextracted with ethyl acetate
11. washThe combined extracts were washed with water and brine successively
12. dry with materialdried over magnesium sulfate
13. customevaporated under reduced pressure
14. dissolutionThe obtained residue was dissolved in ethyl acetate
15. additiontreated with 4N hydrogen chloride in ethyl acetate (0.2 ml) at room temperature
16. additionThe mixture was added hexane
17. filtrationfiltered
18. customdried over reduced pressure