反应详情

To a cold solution of 2-{4-[2-tert-butoxycarbonylamino-3-(4-fluorophenyl)-propionyl]-3-ethyl-piperazin-1-yl}-3-naphthalen-2-yl-propionic acid, 36, (1.7 g, 3.0 mmol) and benzotriazole-1-yl-oxy-tris-pyrrolidinol-phosphonium hexafluorophosphate (PyBOP) (2.0 g, 3.8 mmol) in anhydrous dichloromethane (10 mL) are added 2 M methyl amine solution in THF (1.5 mL, 3.0 mmol) and triethyl amine (1.0 mL, 7.4 mmol). The reaction mixture is placed in a refrigerator overnight. EtOAc (50 mL) and water (200 mL) are added, and the organic layer is separated. The aqueous layer is extracted with EtOAc (3×100 mL). The combined organic layers are washed with brine (100 mL), dried over Na2SO4, and concentrated in vacuo. The crude product is purified over silica (EtOAc/hexane, 1:1) to afford 1.3 g (73% yield) of the desired product. 1H NMR (CDCl3, 300 MHz, δ): 7.75–7.65 (m, 3H), 7.55 (s, 1H), 7.39–7.29 (m, 2H), 7.29–7.2 (m, 1H), 7.10–7.02 (m, 2H), 6.90–6.82 (m, 2H), 6.51–6.30 (m, 1H), 5.31 (d, J=10.4 Hz, 1H), 4.85–4.15 (m, 2.5H), 3.55–3.12 (m, 3H), 3.00–2.05 (m, 10H), 1.85–1.45 (m, 10H), 0.7 (m, 3H); 13C NMR, (CDCl3, 300 MHz) δ 174.0, 172.0, 171.0, 170.0, 163.9, 160.6, 155.2, 137.4, 133.8, 132.4, 131.5, 131.4, 131.3, 131.2, 128.4, 128.0, 127.8, 126.4, 125.8, 116.0, 115.7, 115.4, 80.0, 70.9, 70.7, 60.7, 55.4, 52.1, 51.2, 51.0, 50.5, 49.8, 41.9, 40.2, 39.4, 38.0, 32.4, 28.6, 26.3, 23.3, 22.3, 21.4, 14.5, 10.8, 10.3.

1. customis placed in a refrigerator overnight
2. customthe organic layer is separated
3. extractionThe aqueous layer is extracted with EtOAc (3×100 mL)
4. washThe combined organic layers are washed with brine (100 mL)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated in vacuo
7. customThe crude product is purified over silica (EtOAc/hexane, 1:1)