Triethyl Phosphate → 4-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(ethylsulfonyl)benzonitrile

温度

50 °C

A mixture of triethyl phosphate (4.6 mL, 26.9 mmol) and phosphorous pentoxide (2.54 g, 17.9 mmol) is heated at 50° C. over night and dilutet with tert-butyl methyl ether (45 mL). Cyclohexane-1,3-dione (3.77 g, 33.6 mmol), 3-(ethylsulfonyl)-4-formylbenzonitrile (5.00 g, 22.4 mmol) and 1-(3-(trifluoromethyl)phenyl)urea (4.57 g, 22.4 mmol) are added, and the mixture is heated at reflux for 4 h. The mixture is cooled at room temperature and concentrated under reduced pressure. The residue is purified by reversed phase HPLC (Agilent ZORBAX™ SB-C18, gradient of acetonitrile in water, 0.15% formic acid). Yield: 930 mg; ESI mass spectrum [M+H]+=504; Retention time HPLC: 1.02 min (Z017_S04).

1. temperaturethe mixture is heated
2. temperatureat reflux for 4 h
3. temperatureThe mixture is cooled at room temperature
4. concentrationconcentrated under reduced pressure
5. customThe residue is purified by reversed phase HPLC (Agilent ZORBAX™ SB-C18, gradient of acetonitrile in water, 0.15% formic acid)
6. custom1.02 min (Z017_S04)

ORDレコード

ord-b748e31193424503b6b1460c49870459

出典データセット

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09115093B2