反应详情

The pyrazole of Example 60 (200 mg, 0.829 mmol) and 2-chloroethylamine hydrochloride (144 mg, 1.24 mmol) were heated as a melt at 150° C. for 17 hours. After cooling the solid was dissolved in saturated aqueous sodium hydrogencarbonate (15 ml) and extracted with dichloromethane (2×10 ml). The combined organic phases were washed with 2M aqueous hydrochloric acid (20 ml) and the aqueous layer was neutralised with solid sodium carbonate and extracted with dichloromethane (3×10 ml). The combined organic phases were dried over magnesium sulphate, filtered and concentrated under reduced pressure to leave an orange gum. The crude product was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol (90:10) then dichloromethane:methanol:ammonia (90:9:1, by volume) to provide the title compound (124 mg) as a pale yellow oil.

1. temperatureAfter cooling the solid
2. extractionextracted with dichloromethane (2×10 ml)
3. washThe combined organic phases were washed with 2M aqueous hydrochloric acid (20 ml)
4. extractionextracted with dichloromethane (3×10 ml)
5. dry with materialThe combined organic phases were dried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto leave an orange gum
9. customThe crude product was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol (90:10)