反应详情

A mixture of tert-butyl 2-{4-[(3-amino-2-chloro-6-methyl-4-pyridinyl)amino]phenyl}ethylcarbamate (step 2, 238 mg, 0.63 mmol), propionyl chloride (70 mg, 0.76 mmol) in toluene (4.6 ml) and dichloromethane (0.6 ml) was heated at reflux temperature for 1 h. After cooling, the mixture was diluted with ethyl acetate (100 ml) and washed with 1N aqueous NaOH solution (30 ml×2) and brine (30 ml). The organic layer was dried (MgSO4), and concentrated. The residue and p-toluenesulfonic acid monohydrate (5 mg, 0.026 mmol) in toluene (5.0 ml) was heated at reflux temperature for 16 h. After cooling, the mixture was diluted with dichloromethane (100 ml) and washed with saturated aqueous NaHCO3 solution (30 ml) and brine (30 ml). The organic layer was dried (MgSO4), and concentrated. Purification by PTLC eluting with hexane/ethyl acetate (1:1) to afford 90 mg (34%) of the title compound as a brown oil.

1. temperaturewas heated
2. temperatureat reflux temperature for 1 h
3. temperatureAfter cooling
4. washwashed with 1N aqueous NaOH solution (30 ml×2) and brine (30 ml)
5. dry with materialThe organic layer was dried (MgSO4)
6. concentrationconcentrated
7. temperatureat reflux temperature for 16 h
8. temperatureAfter cooling
9. washwashed with saturated aqueous NaHCO3 solution (30 ml) and brine (30 ml)
10. dry with materialThe organic layer was dried (MgSO4)
11. concentrationconcentrated
12. customPurification by PTLC
13. washeluting with hexane/ethyl acetate (1:1)