反应详情

To a solution of [2-(2,5-dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (52.3 mg, 0.125 mmol, 1.0 equiv; Example 147) in methanol (0.5 mL) was added cyclobutanone (188 mg, 0.2 mL, 2.68 mmol, 21.4 equiv; [CAS RN 1191-95-3]), acetic acid (28 mg, 27 μL, 0.5 mmol, 4.0 equiv; [CAS RN 64-19-7]) and the reaction mixture stirred at rt. After 90 min, sodium cyanoborohydride (15.7 mg, 0.25 mmol, 2.0 equiv; [CAS RN 25895-60-7]) was added and stirring at rt continued for 18 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 3.3 mg (6%) of the title compound. MS (ISP): 474.1 [M+H]+.

1. stirringstirring at rt
2. waitcontinued for 18 h
3. customRemoval of the solvent mixture
4. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
5. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
6. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water