Sodium hydride → tert-butyl (1-(4-(2-(6-oxo-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-5-yl)acetyl)phenyl)cyclobutyl)carbamate

温度

0 °C

5H-benzo[e]pyrido[3,2-b][1,4]diazepin-6(11H)-one (0.362 g, 1.05 eq.) was suspended in dimethylformamide (DMF) (5 mL). The reaction was cooled to 0° C. and sodium hydride (60% in mineral oil) (0.2 g, 3.0 eq.) was added. The reaction was warmed to room temperature and stirred until gas evolution ceased. The reaction was cooled to 0° C. and tert-butyl (1-(4-(2-bromoacetyl)phenyl)cyclobutyl)carbamate (0.6 g, 1.0 eq.) in DMF (1 mL) was added. The reaction was stirred at room temperature overnight. The reaction was quenched by the addition of aqueous saturated ammonium chloride solution (1 mL). Dichloromethane was added (15 mL) and the phases were separated. The organic phase was washed with water (3×10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was purified by column chromatography (50% ethyl acetate in dichloromethane), giving tert-butyl (1-(4-(2-(6-oxo-6,11-dihydro-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-5-yl)acetyl)phenyl)cyclobutyl)carbamate (0.4 g, 50%) as a yellow semi-solid. LCMS: 499 [M+H].

1. temperatureThe reaction was warmed to room temperature
2. temperatureThe reaction was cooled to 0° C.
3. stirringThe reaction was stirred at room temperature overnight
4. customThe reaction was quenched by the addition of aqueous saturated ammonium chloride solution (1 mL)
5. additionDichloromethane was added (15 mL)
6. customthe phases were separated
7. washThe organic phase was washed with water (3×10 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe product was purified by column chromatography (50% ethyl acetate in dichloromethane)

ORDレコード

ord-0077da557dfb4858b9367a6987687c54

出典データセット

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08569331B2