反应详情

温度

50 °C

4-Methyl-1,2,5-oxadiazole-3-carboxylic acid (0.3 g, 2.34 mmol) was stirred in thionyl chloride (10 ml) at 50° C. for 18 hours. A further 3 ml oxalyl chloride and 2 drops of dimethylformamide were added and the reaction stirred for a further 1.5 hours at 50° C. The reaction was concentrated in vacuo and azeotroped with dichloromethane. The residue (0.134 g, 0.915 mmol) was dissolved in CH3CN (1.83 ml) and added to a solution of 3-(2,5-dichloro-3-methoxyphenyl)-pyridine-2,6-diamine (Preparation 4, 0.200 g, 0.704 mmol) in anhydrous pyridine (10 ml). The reaction was heated at 60° C. for 24 hours. A further 0.88 equivalents of the acid chloride in CH3CN (0.091 g, in 1.2 ml) was added and the reaction stirred for a further 24 hours at 60° C. The reaction was partitioned between dichloromethane and a saturated aqueous solution of NaHCO3 before drying over Na2SO4 and concentrating in vacuo. The residue was purified by silica gel column chromatography eluting with 5:95 to 30:70 ethyl acetate:heptane to afford the title compound (0.050 g, 18% yield).

1. concentrationThe reaction was concentrated in vacuo
2. customazeotroped with dichloromethane
3. temperatureThe reaction was heated at 60° C. for 24 hours
4. stirringthe reaction stirred for a further 24 hours at 60° C
5. customThe reaction was partitioned between dichloromethane
6. dry with materiala saturated aqueous solution of NaHCO3 before drying over Na2SO4
7. concentrationconcentrating in vacuo
8. customThe residue was purified by silica gel column chromatography
9. washeluting with 5:95 to 30:70 ethyl acetate