反应详情

To 4-(benzo[d]thiazol-2-ylamino)phenol (0.327 g, 1.35 mmol) dissolved in N-Methyl-2-pyrrolidinone (3 mL) was added sodium hydride, 60% dispersion in mineral oil (54 mg, 1.4 mmol). After stirring at RT for 10 min, 1-(4-(2-fluoropyridin-3-yl)piperidin-1-yl)ethanone (0.15 g, 0.68 mmol) was added and the reaction mixture was stirred at 140° C. for 16 h. After cooling to RT, the reaction mixture was partitioned between EtOAc and brine. The aqueous layer was back extracted with EtOAc (3×) and the combined organics were dried (Na2SO4) and concentrated. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 10% to 100% EtOAc in hexane, followed by trituration with Et2O and hexane to provide 1-(4-(2-(4-(benzo[d]thiazol-2-ylamino)phenoxy)pyridin-3-yl)piperidin-1-yl)ethanone (0.137 g, 0.308 mmol, 45.7% yield) as off-white solid. MS (ESI, pos. ion) m/z: 445.0 (M+1). IC50 (uM) +++++.

1. stirringthe reaction mixture was stirred at 140° C. for 16 h
2. temperatureAfter cooling to RT
3. customthe reaction mixture was partitioned between EtOAc and brine
4. extractionThe aqueous layer was back extracted with EtOAc (3×)
5. dry with materialthe combined organics were dried (Na2SO4)
6. concentrationconcentrated
7. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
8. washeluting with a gradient of 10% to 100% EtOAc in hexane