Methyl chloroformate → 6-bromo-1-(2-morpholinoethyl)quinazolin-2(1H)-one

温度

0 °C

To a stirred solution of 5-bromo-2-(2-morpholinoethylamino)benzonitrile (0.5521 g, 1.8 mmol) in THF (0.13 g, 1.8 mmol) was added bis(iso-butyl)aluminum hydride (2.4 ml, 3.6 mmol) at 0° C. and the resulting bright yellow-orange solution was stirred at 0° C. for 1 h. Methyl chloroformate (0.17 ml, 2.1 mmol) was added to the reaction at 0° C. The mixture was stirred at RT for 2 h, then treated with potassium tert-butoxide 1M THF (3.6 ml, 3.6 mmol) and heated to 60° C. for 5 h. After cooling, the reaction was quenched with NH4Cl(aq) and water (10 mL each) and the separated aqueous layer was extracted with EtOAc (3×10 mL). The combined organic phases were washed with brine, dried (Na2SO4), and concentrated to give a crude residue. Flash column chromatographic purification (eluting with 100% DCM to 3% MeOH in DCM gradient) provided 6-bromo-1-(2-morpholinoethyl)quinazolin-2(1H)-one as a sticky colorless oil. MS m/e 338 (M+H)+.

1. stirringThe mixture was stirred at RT for 2 h
2. temperatureheated to 60° C. for 5 h
3. temperatureAfter cooling
4. customthe reaction was quenched with NH4Cl(aq) and water (10 mL each)
5. extractionthe separated aqueous layer was extracted with EtOAc (3×10 mL)
6. washThe combined organic phases were washed with brine
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated
9. customto give a crude residue
10. customFlash column chromatographic purification (eluting with 100% DCM to 3% MeOH in DCM gradient)

ORDレコード

ord-bb83f0a2b7414dffb55e579ea6dcf4a9

出典データセット

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07935709B2