反应详情

温度

80 °C

tert-Butyl 3-((5-amino-2-(5-cyanopyrazin-2-ylamino)pyridin-4-ylamino)methyl)piperidine-1-carboxylate (121 mg, 0.285 mmol) was dissolved in DCE (6 mL) and 2,5-dimethoxytetrahydrofuran (75.3 mg, 0.57 mmol) and acetic acid (2 mL) were added. The solution was heated for 1 h at 80° C. then a further aliquot of acetic acid (2 mL) was added. The solution was heated at 80° C. for a further 30 min then cooled to room temperature and partitioned between dichloromethane and water. The aqueous phase was extracted with dichloromethane and the combined organic phases were evaporated to give an orange oil. The residue was dissolved in methanol and absorbed onto a TsOH solid phase extraction cartridge, washed once with methanol and allowed to stand for 1 h. The cartridge was then eluted with a solution of 7M ammonia in methanol and the solution was evaporated to dryness. The residue was purified by HPLC to give 5-(4-(piperidin-3-ylmethylamino)-5-(1H-pyrrol-1-yl)pyridin-2-ylamino)pyrazine-2-carbonitrile (4.3 mg, 4%).

1. temperatureThe solution was heated at 80° C. for a further 30 min
2. temperaturethen cooled to room temperature
3. custompartitioned between dichloromethane and water
4. extractionThe aqueous phase was extracted with dichloromethane
5. customthe combined organic phases were evaporated
6. customto give an orange oil
7. customabsorbed onto a TsOH solid phase extraction cartridge
8. washwashed once with methanol
9. washThe cartridge was then eluted with a solution of 7M ammonia in methanol
10. customthe solution was evaporated to dryness
11. customThe residue was purified by HPLC