反应详情

温度

23 °C

To a solution of commercially available 5-cyanopicolinic acid (55.5 mg, 375 μmol) in methanol (5 ml) was added at 0° C. 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (129 mg, 437 μmol) and the colourless solution was stirred at 0° C. for 30 min. Then a solution of (S)-4-(5-amino-2-fluorophenyl)-4-(difluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (intermediate E9.1) (81 mg, 312 μmol) in methanol (5 ml) was added dropwise at 0° C. via syringe. The reaction mixture was stirred at 23° C. for 16 h. Poured into 1 M Na2CO3-sol., extracted with dichloromethane, washed the organic layer with brine and dried over Na2SO4. Removal of the solvent in vacuum left a light brown oil which was chromatographed on 20 g silica gel with dichloromethane/methanol 0-10% to give (S)—N-(3-(2-amino-4-(difluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-cyanopicolinamide (89 mg, 229 μmol, 73.2% yield) as a white solid. MS (ISP): m/z=390.0 [M+H]+.

1. extraction, extracted with dichloromethane
2. washwashed the organic layer with brine
3. dry with materialdried over Na2SO4
4. customRemoval of the solvent in vacuum
5. waitleft a light brown oil which
6. customwas chromatographed on 20 g silica gel with dichloromethane/methanol 0-10%