反应详情

3-[2-(2,5-Dichloro-pyrimidin-4-ylamino)-5-morpholin-4-yl-phenoxy]-propionitrile (84 mg, 0.00021 mol), 3-(2-Methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (47 mg, 0.00021 mol), and 10-Camphorsulfonic acid (58 mg, 0.00025 mol) in Isopropyl alcohol (2.0 mL) was irradiated in a CEM microwave (140° C., 30 min) The mixture was diluted with 2 mL water and 0.5 mL satd. sodium bicarbonate, then extracted 2×10 mL DCM, dried over sodium sulfate and conc. onto 1 g Celite. Chromatography (ISCO, Amine-capped SiO2, 14 g, 25-100% EtOAc:Hex) afforded 3-(2-{5-Chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-5-morpholin-4-yl-phenoxy)-propionitrile as a light pink solid (91 mg, 74%). MP: 91-96° C., LCMS 578 (M+H); 1H-NMR (CDCl3): 8.23 (d, 1H, J=8.8 Hz), 8.02 (s, 1H), 7.52 (s, 1H), 7.37 (s, 1H), 7.18 (d, 1H, J=7.9 Hz), 7.00 (d, 1H, J=8.0 Hz), 6.85 (s, 1H), 6.56 (d, 1H, J=8.8 Hz), 6.50 (s, 1H), 4.28 (t, 2H, J=6.3 Hz), 3.88 (m, 4H), 3.53 (t, 2H, J=6.3 Hz), 3.38 (s, 3H), 3.14 (m, 4H), 2.90 (m, 6H), 2.72 (m, 6H).

1. extractionsodium bicarbonate, then extracted 2×10 mL DCM
2. dry with materialdried over sodium sulfate and conc. onto 1 g Celite
3. customChromatography (ISCO, Amine-capped SiO2, 14 g, 25-100% EtOAc:Hex)