反应详情

A mixture of 3-(methylamino)-5-(1H-pyrazol-4-yl)thiophene-2-carboxamide dihydrochloride (145 mg, 0.491 mmol), saturated aqueous NaHCO3 (50 mL) and EtOAc (50 mL) was shaken well. The organic layer was collected, dried over MgSO4, filtered and concentrated under reduced pressure. This residue was mixed with cyclohexanone (2 mL, 19.3 mmol), PTSA (93 mg, 0.491 mmol), MgSO4 (118 mg, 0.982 mmol) and DMF (2 mL). This mixture was stirred at 80° C. overnight. The mixture was poured into saturated aqueous NaHCO3 and extracted with 3:1 EtOAc/THF (100 mL), and the extract was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc then to 90:10 EtOAc/MeOH) to afford a yellow solid. This solid was triturated with EtOAc/hexane, and the precipitate was collected by filtration to afford the title compound (24.5 mg, 16%) as a yellow solid:

1. customThe organic layer was collected
2. dry with materialdried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. stirringThis mixture was stirred at 80° C. overnight
6. extractionextracted with 3:1 EtOAc/THF (100 mL)
7. dry with materialthe extract was dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by column chromatography (Purif, silica gel, 95:5 hexane/EtOAc to EtOAc
11. customto 90:10 EtOAc/MeOH) to afford a yellow solid
12. customThis solid was triturated with EtOAc/hexane
13. filtrationthe precipitate was collected by filtration