Triethylamine → 4-ethyl-6-chloro-4-phenyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

Temperature

0 °C

To a −20° C. solution of 6-chloro-4-hydroxy-4-phenyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one (5.5 g, 15 mmol) in THF (50 mL) was added triethylamine (10.7 mL, 77 mmol) and then thionyl chloride (1.2 mL, 17 mmol) was added dropwise. After 20 min, 1M ethylmagnesium bromide in THF (46 mL, 46 mmol) was added over 10 min. and the reaction mixture warmed to 0° C. After an additional 30 min at 0° C., the reaction was quenched by pouring into a well stirred mixture of 300 mL EtOAc and 200 mL water which was acidified with 1N HCl solution. The layers were mixed and separated and the organic layer washed with 200 mL brine and filtered to remove unreacted starting material. The filtrate was concentrated in vacuo. Purification by normal phase chromatography (120 g silica gel cartridge, 10-75% EtOAc/hexanes) provided 4-ethyl-6-chloro-4-phenyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one. 1H NMR (CDCl3, 400 MHz) δ 8.73 (s, NH); 7.39 (m, 3H); 7.35 (m, 2H); 7.09 (dd, 1H, J=8.43 and 2.2 Hz); 6.70 (d, 1H, J=8.43 Hz); 6.49 (d, 1H, J=2.38 Hz); 3.92 (dq, 1H, J=9.52 and 15.9 Hz); 3.47 (dq, 1H, J=8.61 and 17 Hz); 2.41 (dq, 1H, J=7.14 and 14.29 Hz); 2.28 (dq, 1H, J=7.14 and 14.28 Hz); 0.91 (t, J=7.14 Hz, 3H); MS (Electrospray): m/z 369.2 (M+H)

1. waitAfter an additional 30 min at 0° C.
2. customthe reaction was quenched
3. additionby pouring into a well
4. additionmixture of 300 mL EtOAc and 200 mL water which
5. additionThe layers were mixed
6. customseparated
7. washthe organic layer washed with 200 mL brine
8. filtrationfiltered
9. customto remove unreacted
10. concentrationThe filtrate was concentrated in vacuo
11. customPurification by normal phase chromatography (120 g silica gel cartridge, 10-75% EtOAc/hexanes)

ORD record

ord-5241519c39b840f5ae9cbc9842c49b62

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07745452B2