反应详情

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 dichloromethane (1.5 mL) was added 3,4-dihydro-2H-benzo[1,4]oxazine (22.9 mg, 0.17 mmol, 1.1 equiv; [CAS RN 5735-53-5]), triethylamine (30.4 mg, 42 μL, 0.3 mmol, 2.0 equiv; [CAS RN 121-44-8]) and 2-chloro-1-methylpyridinium iodide (42.2 mg, 0.17 mmol, 1.1 equiv; [CAS RN 14338-32-0]). The reaction mixture was stirred at rt 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 11 mg (18%) of the title compound. MS (ISP): 401.0 [M+H]+.

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