反应详情

A solution of (8-chloro-1-cyclopropyl-6,7-difluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)carbamic acid tert-butyl ester (Example 14, 0.37 g, 0.97 mmol) in acetonitrile (20 mL) is added pyrrolidin-3-yl-methylamine (0.115 g, 1.16 mmol) and triethylamine (2.7 mL, 19.3 mmol). After refluxing for 20 hours, the reaction mixture is cooled to room temperature and diluted with ethyl acetate. The organic layer is washed with saturated sodium bicarbonate, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate concentrated. The resulting residue is redissolved in methylene chloride (10 mL) at 0° C. and while stirring, triethylamine (0.33 mL, 2.34 mmol) and methanesulfonyl chloride (0.072 mL, 0.94 mmol) is added. After 2 hours, the reaction mixture is diluted with ethyl acetate and washed with saturated sodium bicarbonate, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate concentrated and the product is purified via flash column chromatography (1:1 EtOAc/hexanes) to afford {8-chloro-1-cyclopropyl-6-fluoro-7-[3-(methanesulfonylaminomethyl)pyrrolidin-1-yl]-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}carbamic acid tert-butyl ester (0.043 g). MS CI: m/e 446 ((MH+)-Boc).

1. temperatureAfter refluxing for 20 hours
2. washThe organic layer is washed with saturated sodium bicarbonate, water, and brine
3. dry with materialThe organic layer is dried over MgSO4
4. filtrationfiltered
5. concentrationthe filtrate concentrated
6. dissolutionThe resulting residue is redissolved in methylene chloride (10 mL) at 0° C.
7. washwashed with saturated sodium bicarbonate, water, and brine
8. dry with materialThe organic layer is dried over MgSO4
9. filtrationfiltered
10. concentrationthe filtrate concentrated
11. customthe product is purified via flash column chromatography (1:1 EtOAc/hexanes)