反应详情

(S)-3-(4-bromo-2-fluoro-5-methylphenoxy)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (200 mg, 0.42 mmol), trans-cyclohexane-1,2-diamine (20 μL, 0.17 mmol), sodium methanesulfinate (64 mg, 0.63 mmol) was dissolved in DMSO (3 mL) and nitrogen bubbled through for 15 minutes. Cu(I) triflate benzene-complex (21 mg, 0.04 mmol) was added and the reaction was plunged into 110° C. oil bath and stirred under nitrogen overnight. Additional trans-cyclohexane-1,2-diamine (20 μL, 0.17 mmol), sodium methanesulfinate (64 mg, 0.63 mmol) and Cu(I) triflate benzene-complex (21 mg, 0.04 mmol) were added and stirred for another 4 hours at 110° C. The reaction was cooled to ambient temperature, partitioned between water and EtOAc, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (100% EtOAc) to afford (S)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenoxy)pyrrolidin-2-one (119.8 mg, 0.25 mmol, 60% yield) as a white solid. Mass spectrum (apci) m/z=477.3 (M+H).

1. customnitrogen bubbled through for 15 minutes
2. customwas plunged into 110° C.
3. stirringstirred for another 4 hours at 110° C
4. custompartitioned between water and EtOAc
5. extractionextracted with EtOAc
6. washwashed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified over silica gel (100% EtOAc)