反应详情

To a solution of [3,5-bis(trifluoromethyl)benzyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amine (8.3 mg, 0.015 mmol) (Example 20) and methanesulfonyl chloride (10.5 μL, 0.135 mmol) in CH2Cl2 (500 μL) was added N,N-diisopropylethylamine (47.4 μL, 0.273 mmol). The reaction was stirred at room temperature for twenty minutes and then was poured into H2O (10 mL). The mixture was extracted with EtOAc (50 mL), and the organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 50% CH2Cl2/hexanes afforded N-[3,5-bis(trifluoromethyl)benzyl]-N-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}methanesulfonamide. Rf=0.20 (50% CH2Cl2/hexanes). LCMS=628.3 (M+1)+. 1H NMR (CDCl3, 600 MHz) δ 7.69 (s, 1H), 7.55 (s, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.47 (s, 2H), 7.28-7.30 (m, 2H), 6.94 (d, J=9.0 Hz, 1H), 6.92 (d, J=1.8 Hz, 1H), 4.44 (d, J=15.0, 1H), 4.32 (d, J=15.0 Hz, 1H), 4.19 (d, J=15.6 Hz, 1H), 4.14 (d, J=15.6 Hz, 1H), 3.72 (s, 3H), 2.89 (m, 1H), 2.69 (s, 3H), 1.21-1.25 (m, 6H).

1. extractionThe mixture was extracted with EtOAc (50 mL)
2. washthe organic extracts were washed with brine (10 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customPurification by flash chromatography with 50% CH2Cl2/hexanes