Methyl iodide → 2-(2,5-Dichloro-phenoxy)-N-(2-ethyl-phenyl)-N-methyl-nicotinamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(2,5-dichloro-phenoxy)-nicotinic acid (59.7 mg, 0.21 mmol, 1.0 equiv; Example 31, Step 1) in dichloromethane (2.0 mL) was added 2-ethyl-phenylamine (27.9 mg, 0.23 mmol, 1.1 equiv; [CAS RN 578-54-1]), triethylamine (42.5 mg, 59 μL, 0.42 mmol, 2.0 equiv; [CAS RN 121-44-8]) and 2-chloro-1-methylpyridinium iodide (59.0 mg, 0.23 mmol, 1.1 equiv; [CAS RN 14338-32-0]) and the reaction mixture stirred at 40° C. over night. The solvent was removed by evaporation under reduced pressure and the crude reaction mixture redissolved in DMF (1 mL). To this solution was added sodium hydride (13.8 mg, 0.32 mmol, 1.5 equiv; 55% free-flowing powder moistened with oil; [CAS RN 7646-69-7]) and iodomethane (59.6 mg, 26 μL, 0.42 mmol, 2.0 equiv; [CAS RN 74-88-4]) and the reaction mixture stirred at 35° C. for 1 h. 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 6.9 mg (8%) of the title compound. MS (ISP): 401.2 [M+H]+.

Provenance & Evidence