Methyl iodide → N-(2,6-Dichloro-3-methoxy-phenyl)-2-(2,5-dichloro-phenoxy)-5-fluoro-N-methyl-nicotinamide

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Reaction Steps

To a solution of 2-(2,5-dichloro-phenoxy)-5-fluoro-nicotinoyl chloride (76.6 mg, 0.24 mmol, 1.0 equiv) in anhydrous DMF (1 mL) was added N-ethyldiisopropylamine (155 mg, 205 μL, 1.2 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and 2,6-dichloro-3-methoxy-phenylamine (50.7 mg, 0.264 mmol, 1.1 equiv; [CAS RN 55285-43-3]) and the reaction mixture stirred at rt over night. To this solution was added sodium hydride (20.6 mg, 0.48 mmol, 2.0 equiv; 55% free-flowing powder moistened with oil; [CAS RN 7646-69-7]) and iodomethane (68.2 mg, 29 μL, 0.48 mmol, 2.0 equiv; [CAS RN 74-88-4]) and stirring of the reaction mixture at rt continued for 2 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 8.1 mg (7%) of the title compound as an off-white powder. MS (ISP): 490.9 [M+H]+.

Provenance & Evidence