反应详情

To a solution of 3-bromo-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide (Intermediate X) (0.033 g, 0.077 mmol) in 0.80 mL degassed DMF (degassed by bubbling a stream of argon through solvent for 5 min) was added Zn(CN)2 (0.011 g, 0.092 mmol) and Pd(PPh3)4 (0.009 g, 0.008 mmol). The reaction vessel was purged thoroughly with argon, then sealed and microwaved at 180° C. for 30 min. The reaction was diluted with EtOAc, and the organics were washed with 3M aqueous LiCl. The aqueous washed with fresh EtOAc (2×), the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography (5->75% EtOAc/hexanes) to afford 3-cyano-N-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzamide as a white foam. 1H NMR (CDCl3, 400 MHz) δ 8.04 (t, J=2.0 Hz, 1H), 7.91 (t, J=1.3 Hz, 1H), 7.78 (t, J=1.5 Hz, 1H), 7.36-7.7.31 (m, 2H), 7.05-7.00 (m, 2H), 6.67 (d, J=7.5 Hz, 1H), 5.25 (q, J=7.1 Hz, 1H), 3.34 (s, 3H), 2.87 (s, 3H), 1.59 (d, J=7.0 Hz, 3H). LCMS [M+H]+=376.

1. customdegassed
2. customby bubbling a stream of argon through solvent for 5 min)
3. customThe reaction vessel was purged thoroughly with argon
4. customsealed
5. custommicrowaved at 180° C. for 30 min
6. additionThe reaction was diluted with EtOAc
7. washthe organics were washed with 3M aqueous LiCl
8. washThe aqueous washed with fresh EtOAc (2×)
9. washthe combined organics were washed with brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe residue was purified by silica gel chromatography (5->75% EtOAc/hexanes)