反应详情

To a solution of 2-(4-bromo-2,5-dichloro-phenoxy)-nicotinic acid (50 mg, 0.14 mmol, 1.0 equiv; Example 163, Step 1) in anhydrous dichloromethane (1.5 mL) was added N-ethyldiisopropylamine (152 mg, 200 μL, 1.18 mmol, 8.4 equiv; [CAS RN 7087-68-5]) and 2-chloro-1-methylpyridinium iodide (42 mg, 0.17 mmol, 1.2 equiv; [CAS RN 14338-32-0]) and the reaction mixture stirred at rt. After 1 h, 1,2,3,4-tetrahydro-quinoline (22 mg, 21 μL, 0.17 mmol, 1.2 equiv; [CAS RN 635-46-1]) was added and stirring at rt continued over night. 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 41 mg (61%) of the title compound as a white powder. MS (ISP): 476.9 [M+H]+.

1. stirringstirring at rt
2. waitcontinued over night
3. customRemoval of the solvent mixture
4. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
5. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
6. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water