반응 #10439

반응 방정식

(8-chloro-1-cyclopropyl-6,7-difluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)carbamic acid tert-butyl ester

(8-Chloro-1-cyclopropyl-6,7-difluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)carbamic acid tert-butyl ester

pyrrolidin-3-yl-methylamine

triethylamine

triethylamine

methanesulfonyl chloride

→

{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

수율 8.4%

용매

ethyl acetate

ethyl acetate

acetonitrile

반응 조건

후처리

1. 1
   온도After refluxing for 20 hours
2. 2
   세척The organic layer is washed with saturated sodium bicarbonate, water, and brine
3. 3
   건조The organic layer is dried over MgSO4
4. 4
   여과filtered
5. 5
   농축the filtrate concentrated
6. 6
   workup.DISSOLUTIONThe resulting residue is redissolved in methylene chloride (10 mL) at 0° C.
7. 7
   세척washed with saturated sodium bicarbonate, water, and brine
8. 8
   건조The organic layer is dried over MgSO4
9. 9
   여과filtered
10. 10
    농축the filtrate concentrated
11. 11
    기타the product is purified via flash column chromatography (1:1 EtOAc/hexanes)

실험 절차

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).

출처