반응 #10405

반응 방정식

iodomethane

{7-[(S)-3-(tert-butoxycarbonyl-N-methylamino)-pyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}carbamic acid tert-butyl ester

sodium hydride

→

title compound

수율 48.2%

{7-[(S)-3-(tert-Butoxycarbonyl-N-methylamino)pyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}-methylcarbamic acid tert-butyl ester

수율 48.2%

용매

ethyl acetate

N,N-dimethylformamide

반응 조건

후처리

1. 1
   workup.WAITAfter 1 hour
2. 2
   세척washed with saturated ammonium chloride solution, water, and brine
3. 3
   건조The organic layer is dried over MgSO4
4. 4
   여과filtered
5. 5
   농축the filtrate concentrated
6. 6
   기타The resulting residue is purified by flash column chromatography (1:1 ethyl acetate/hexanes)

실험 절차

To a solution of {7-[(S)-3-(tert-butoxycarbonyl-N-methylamino)-pyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl}carbamic acid tert-butyl ester from Example 8 (0.238 g, 0.421 mmol) in N,N-dimethylformamide (5 mL) at −78° C. under nitrogen atmosphere is added sodium hydride (60% dispersion in mineral oil, 0.025 g, 0.631 mmol). After 30 minutes, iodomethane (0.052 mL, 0.842 mmol) is added, and the reaction mixture is warmed to room temperature. After 1 hour, the reaction mixture is diluted with ethyl acetate and washed with saturated ammonium chloride solution, water, and brine. The organic layer is dried over MgSO4, filtered, and the filtrate concentrated. The resulting residue is purified by flash column chromatography (1:1 ethyl acetate/hexanes) to afford the title compound (0.118 g). 1H NMR (CDCl3): δ 7.63 (dd, 1H), 4.78 (bs, 1H), 3.87–3.45 (m, 6H), 2.62–2.44 (m, 6H), 2.31–2.12 (m, 2H), 1.49–1.47 (m, 18H), 1.23–1.07 (m, 2H), 0.75–0.53 (m, 2H). MS CI: m/z 582 (MH+).

출처