反应详情

To a solution of 2-methyl-3-[4-[6-(trifluoromethyl) quinolin-2-yl]piperazin-1-yl]propanoic acid (100 mg, 0.27 mmol) in dichloromethane (20 ml) was added EDAC.HCl (79 mg, 0.41 mmol, 1.5 eq.), 1H-1,2,3-benzotriazol-1-ol (55.2 mg, 0.41 mmol, 1.5 eq.), triethylamine (82.6 mg, 0.82 mmol, 3 eq.) and N-[4-nitro-3-(trifluoromethyl)phenyl]piperidin-4-amine (94.5 mg, 0.33 mmol, 1.2 eq.). The resulting solution was stirred overnight at room temperature and then quenched by the addition of water (50 ml) and extracted with dichloromethane (3×30 ml). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under vacuum to give a residue, which was purified by Prep-TLC with 5% methanol in dichloromethane to afford of 2-methyl-1-(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]piperidin-1-yl)-3-[4-[6-(trifluoromethyl)quinolin-2-yl]piperazin-1-yl]propan-1-one as a yellow solid (111.2 mg, 64%). (ES, m/z): [M+H]+ 639.40; 1H NMR (300 MHz, CDCl3): δ 7.95-8.08 (m, 1H), 7.72 (overlapping m, 2H), 7.01 (d, J=9.3 Hz, 1H), 6.89 (m, 1H), 6.65 (m, 1H), 4.49-4.70 (m, 2H), 4.08 (m, 1H), 3.72-3.85 (br m, 5H), 3.65 (m, 1H), 3.08 (br s, 1H), 2.88 (br m, 2H), 2.68 (br s, 3H), 2.38 (m, 1H), 2.07-2.20 (overlapping m, 2H), 1.47 (m, 2H), 1.13 (br s, 3H).

1. customquenched by the addition of water (50 ml)
2. extractionextracted with dichloromethane (3×30 ml)
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated under vacuum
5. customto give a residue, which
6. customwas purified by Prep-TLC with 5% methanol in dichloromethane