反应详情

3 mol/L hydrogen chloride-ethyl acetate (30 mL) was added to N-[3,5-bis(trifluoromethyl)benzyl]-N-[2-(t-butoxycarbonylamino)ethyl]-4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylic acid amide (Compound of Reference Example 5; 11.8 g) while the solution was chilled on an ice bath. The reaction mixture was stirred for 1 hour and then additional 1 hour at room temperature. The solvent was removed and the resulting residue was dissolved in N,N-dimethylformamide (20 mL). To this solution, potassium carbonate (5.37 g) was added and the mixture was stirred at 100° C. for 1 hour. The reaction mixture was diluted with ethyl acetate, was sequentially washed with water and a saturated aqueous solution of sodium chloride, and was then dried over anhydrous sodium sulfate. Following removal of the solvent, the residue was purified on a silica gel column chromatography (ethyl acetate:hexane=2:1) to obtain 6-[3,5-bis(trifluoromethyl)benzyl]-4-chloro-2-(methylthio)-5-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-e][1,4]diazepin (6.22 g, 68%).

1. temperaturewas chilled on an ice bath
2. customadditional 1 hour
3. customat room temperature
4. customThe solvent was removed
5. dissolutionthe resulting residue was dissolved in N,N-dimethylformamide (20 mL)
6. additionTo this solution, potassium carbonate (5.37 g) was added
7. stirringthe mixture was stirred at 100° C. for 1 hour
8. additionThe reaction mixture was diluted with ethyl acetate
9. washwas sequentially washed with water
10. dry with materiala saturated aqueous solution of sodium chloride, and was then dried over anhydrous sodium sulfate
11. customremoval of the solvent
12. customthe residue was purified on a silica gel column chromatography (ethyl acetate:hexane=2:1)