Sodium hydride → N-[2-({6-[Cyano(2,6-dichlorophenyl)methyl]pyridazin-3-yl}sulfanyl)benzyl]-3-fluoro-5-(morpholin-4-yl)benzamide

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence