反应详情

温度

24 °C

Nitrogen was bubbled through a suspension of 2 g (9 mmol) of 4-chloro-5-(4-chlorophenoxy)-2-(diisopropylaminomethyleneamino)pyrimidine (see Example 2) in 20 ml of ethanol for 10 minutes. Then 1.15 g (9.34 mmol) of 4-amino-3-methylphenol was added and nitrogen bubbled through the suspension for 5 minutes. The solution was then tightly sealed and stirred at 24° C. for 20 hours. Then 5 ml of concentrated hydrochloric acid was added to the mixture and refluxed for 60 minutes. The mixture was cooled and spin evaporated. The residue was suspended in 100 mL CH2Cl2 and 400 mL water. The pH was adjusted to 12 with 3N NaOH. The organic phase was washed with water (400 mL) twice, brine (200 mL) and then dried over Na2SO4. The salt was removed by filtration and the filtrate applied to a Silica Gel 60 column (2.5×10 cm) preequilibrated with CH2Cl2. The column was eluted with 800 mL CH2Cl2 and then with mixtures of ethylacetate and CH2Cl2. The fractions showing one spot on TLC (EtOAc; Rf0.45) were pooled and concentrated by spin evaporation. The liquor formed crystals on standing. 0.19 g (6% yield) of product, a white solid, was obtained after drying in vacuo at 105° C. for 16 hours, mp 199-201° C.

1. customnitrogen bubbled through the suspension for 5 minutes
2. customThe solution was then tightly sealed
3. additionThen 5 ml of concentrated hydrochloric acid was added to the mixture
4. temperaturerefluxed for 60 minutes
5. temperatureThe mixture was cooled
6. customspin evaporated
7. washThe organic phase was washed with water (400 mL) twice
8. dry with materialbrine (200 mL) and then dried over Na2SO4
9. customThe salt was removed by filtration
10. washThe column was eluted with 800 mL CH2Cl2
11. concentrationconcentrated by spin evaporation
12. customThe liquor formed crystals