反应详情

In a round-bottomed flask, 2-amino-5-(benzyloxy)-N,1-dimethyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide (250 mg, 867 μmol, Eq: 1.00) was combined with THF (20 ml) to give a white suspension. DMF (4 ml) was added followed by potassium tert-butoxide (117 mg, 1.04 mmol, Eq: 1.2). The resulting mixture was stirred at room temperature for 10 min, then cooled with an ice bath. To this was slowly added a solution of (4-chlorophenyl)methanesulfonyl chloride (240 mg, 1.07 mmol, Eq: 1.23) in THF (1 ml). After stirring at room temperature for 14 h, further t-BuOK (234 mgs) was added. The mixture was stirred for 5 min, cooled in the ice bath and then further (4-chlorophenyl)methanesulfonyl chloride (240 mg, 1.07 mmol) was added. The reaction mixture was stirred for 72 hours at RT and then diluted with EtOAc, washed with saturated aqueous NaHCO3 solution and brine. Some solid precipitated in the EtOAc solution and was collected by filtration. The remaining filtrate was evaporated to dryness, purified by flash chromatography (silica gel, 2% to 6% MeOH in DCM) and then triturated by EtOAc/Hex. The solids were combined to give the desired product as a white solid (0.210 g; 51%). LCMS m/z=477 (MH+).

1. customto give a white suspension
2. temperaturecooled with an ice bath
3. stirringAfter stirring at room temperature for 14 h
4. stirringThe mixture was stirred for 5 min
5. stirringThe reaction mixture was stirred for 72 hours at RT
6. washwashed with saturated aqueous NaHCO3 solution and brine
7. customSome solid precipitated in the EtOAc solution
8. filtrationwas collected by filtration
9. customThe remaining filtrate was evaporated to dryness
10. custompurified by flash chromatography (silica gel, 2% to 6% MeOH in DCM)
11. customtriturated by EtOAc/Hex