Methyl iodide → N-(2-Cyclopropyl-phenyl)-2-(2,5-dichloro-phenoxy)-N-methyl-nicotinamide

Beteiligte Stoffe

Reaktionsschritte

To a solution of 2-(2,5-dichloro-phenoxy)-nicotinic acid (42.6 mg, 0.15 mmol, 1.0 equiv; Example 31, Step 1) in anhydrous DMF (1 mL) was added N-ethyldiisopropylamine (97 mg, 128 μL, 0.75 mmol, 5.0 equiv; [CAS RN 7087-68-5]) and HATU (67 mg, 0.18 mmol, 1.2 equiv; [CAS RN 148893-10-1]) and the reaction mixture stirred at rt for 30 min. After addition of 2-cyclopropyl-phenylamine (24 mg, 0.18 mmol, 1.2 equiv; [CAS RN 3158-73-4]) the reaction mixture was heated by microwave irradiation to 100° C. After 30 min, sodium hydride (8.6 mg, 0.2 mmol, 2.0 equiv; 55% free-flowing powder moistened with oil; [CAS RN 7646-69-7]) and iodomethane (28.4 mg, 12 μL, 0.2 mmol, 2.0 equiv; [CAS RN 74-88-4]) were added 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 12.6 mg (20%) of the title compound. MS (ISP): 412.9 [M+H]+.

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