反应详情

A solution of 0.57 g (2.0 mmol) of 3-amino-1-cyclopropyl-6,7-difluoro-8-methoxy-1H-quinazoline-2,4-dione (Example 24d), 0.64 g (3.0 mmol) of ((S)-(R)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester (J. Het. Chem., 1992; 29:1481), 0.81 g (8.0 mmol) of triethylamine and 10 mL of dimethyl sulfoxide is heated at 110° C. for 4 hours. The reaction mixture is cooled to room temperature, poured into 150 mL of ice and water, and extracted with ethyl acetate (2×125 mL). The combined organic layers are washed with water, dried (MgSO4), filtered and evaporated in vacuo to give 1.1 g of crude product. Chromatography on flash grade silica gel (230–400 mesh) eluting with dichloromethane/ethanol (9:1) provided 0.92 g of the title compound, mp 96–98° C.

1. extractionextracted with ethyl acetate (2×125 mL)
2. washThe combined organic layers are washed with water
3. dry with materialdried (MgSO4)
4. filtrationfiltered
5. customevaporated in vacuo
6. customto give 1.1 g of crude product
7. washChromatography on flash grade silica gel (230–400 mesh) eluting with dichloromethane/ethanol (9:1)