反应详情

温度

100 °C

A solution of 3-fluoro-5-(morpholin-4-yl)-N-(2-sulfanylbenzyl)benzamide (80 mg, 0.23 mmol) in DMF (3 mL) was treated with sodium hydride (60% in mineral oil, 8.8 mg, 0.22 mmol). The mixture was stirred for 5 min and treated with a solution of (6-chloro-pyridazin-3-yl)-(2,6-dichloro-phenyl)-acetonitrile (63 mg, 0.21 mmol) in DMF (1 mL). The reaction mixture was heated at 100° C. for 45 min, cooled to RT and partitioned between aqueous saturated NaHCO3 and EtOAc. The aqueous layer was extracted with EtOAc, the combined organic layers were dried over MgSO4, filtered, and the filtrate was concentrated in vacuo. Purification by reverse phase preparative HPLC (water/acetonitrile+0.1% HCO2H 50% isocratic), afforded the title compound (32 mg, 25%) as a yellow oil. LCMS (Method 3): Rt 11.77 min, m/z 608 [MH+]. 1H NMR (400 MHz, CDCl3): 7.67-7.58 (2H, m), 7.53-7.47 (1H, m), 7.45-7.32 (4H, m), 7.31-7.20 (2H, m), 7.09 (1H, t, J 1.7), 6.75 (1H, br t, J 5.6), 6.71-6.61 (2H, m), 6.33 (1H, s), 4.76 (2H, m), 3.86 (4H, t, J 4.8), 3.21 (4H, t, J 4.8).

1. temperaturecooled to RT
2. custompartitioned between aqueous saturated NaHCO3 and EtOAc
3. extractionThe aqueous layer was extracted with EtOAc
4. dry with materialthe combined organic layers were dried over MgSO4
5. filtrationfiltered
6. concentrationthe filtrate was concentrated in vacuo
7. customPurification by reverse phase preparative HPLC (water/acetonitrile+0.1% HCO2H 50% isocratic)