反应详情

To a solution of (2R)-2-[N-(4-chlorobenzenesulfonyl)-N-(piperidin-4-ylmethyl)amino]-4-methyl-pentanoic acid amide (Example 126, 0.10 g, 0.22 mmol) and Et3N (0.06 mL, 0.5 mmol) in CH2Cl2 (3.0 mL) was added isonicotinoyl chloride hydrochloride (56 mg, 0.32 mmol). The reaction was stirred at rt for 18 h and then was poured into a mixture of EtOAc and sat. aq. NaHCO3. The organic solution was separated and washed with brine, dried over MgSO4, and concentrated to an oily residue. The residue was purified on a Biotage 10M (eluted with 80% EtOAc/hexanes) to give a white solid (36 mg, 30%). MS(ESI), (M+H)+509.20; 1H NMR (CDCl3, 500 MHz) δ8.66 (br s, 2H), 7.80 (d, 1H, J=8.6), 7.73 (d, 2H, J=8.5), 7.51 (d, 2H, J=7.6), 7.41 (br s, 1H). 6.64 (br s, 1H), 5.35 (br s, 1H), 4.70 (br s, 1H), 4.10 (br s, 1H), 3.71 (br s, 1H), 3.33 (br s, 1H), 3.02 (dd, 2H, J=4.8, 16), 2.70-2.85 (br s, 1H), 1.50-2.09 (m, 5H), 1.18-1.33 (m, 4H), 0.73 (d, 3H, J=6.7), 0.68 (d, 3H, J=6.5).

1. customThe organic solution was separated
2. washwashed with brine
3. dry with materialdried over MgSO4
4. concentrationconcentrated to an oily residue
5. customThe residue was purified on a Biotage 10M (eluted with 80% EtOAc/hexanes)