반응 #10426

반응 방정식

3-amino-1-cyclopropyl-6,7-difluoro-8-methoxy-1H-quinazoline-2,4-dione

((S)-(R)-1-pyrrolidin-3-ylethyl)carbamic acid tert-butyl ester

triethylamine

dimethyl sulfoxide

→

title compound

수율 96.3%

{(R)-1-[(S)-1-(3-Amino-1-cyclopropyl-6-fluoro-8-methoxy-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-7-yl)pyrrolidin-3-yl]ethyl}-carbamic acid tert-butyl ester

수율 96.3%

용매

water

반응 조건

후처리

1. 1
   추출extracted with ethyl acetate (2×125 mL)
2. 2
   세척The combined organic layers are washed with water
3. 3
   건조dried (MgSO4)
4. 4
   여과filtered
5. 5
   기타evaporated in vacuo
6. 6
   기타to give 1.1 g of crude product
7. 7
   세척Chromatography on flash grade silica gel (230–400 mesh) eluting with dichloromethane/ethanol (9:1)

실험 절차

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.

출처