Magnesium trifluoromethanesulfonate → 6-(3-chlorophenyl)-4-cyclopropyl-4-methyl-3,4-dihydro-1H-quinazolin-2-one

To a solution of 6-(3-chlorophenyl)-4-cyclopropyl-1-(4-methoxybenzyl)-1H-quinazolin-2-one (0.25 g, 0.6 mmol) in anhydrous ether was added, at ambient temperature under nitrogen, magnesium triflate (0.78 g, 2.4 mmol). The mixture was stirred for 30 minutes and treated with a solution of methylmagnesium bromide in ether (3.0 M, 1.0 mL, 3.0 mmol). The reaction mixture was kept at room temperature under nitrogen for 3 hours and quenched with a mixture of a saturated aqueous ammonium chloride solution (10 mL) and 1N aqueous HCl solution (5 mL). The mixture was stirred at room temperature for 20 minutes and ethyl acetate (40 mL) was added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine and dried (MgSO4). The solvent was removed and a half portion of the residue was dissolved in TFA (3 mL) and was stirred under nitrogen at room temperature for 72 hours. The solution was poured onto ice-water and the white precipitate obtained was collected on a filter. The solid was washed with water and then purified by a flash chromatography (methylene chloride:methanol/25:1, silica gel) to give 6-(3-chlorophenyl)-4-cyclopropyl-4-methyl-3,4-dihydro-1H-quinazolin-2-one as off-white solid (40 mg, 43%): mp 125-127° C.; 1H-NMR (DMSO-d6) δ 9.21 (s, 1H), 7.71 (s, 1H), 7.61 (d, 1H, J=7.8 Hz), 7.55 (d, 1H, J=1.6 Hz), 7.47 (dd, 1H, J=8.3, 1.8 Hz), 7.45 (t, 1H, J=7.8 Hz), 7.36 (d, 1H, J=8.1 Hz), 6.84 (d, 1H, J=8.2 Hz), 6.79 (s, 1H), 1.54 (s, 3H), 1.11 (m, 1H), 0.42 (m, 1H), 0.15-0.20 (i, 3H); MS (ESI) m/z 313([M+H]+, 100%).

1. waitThe reaction mixture was kept at room temperature under nitrogen for 3 hours
2. customquenched with a mixture of a saturated aqueous ammonium chloride solution (10 mL) and 1N aqueous HCl solution (5 mL)
3. stirringThe mixture was stirred at room temperature for 20 minutes
4. additionethyl acetate (40 mL) was added
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with ethyl acetate (3×10 mL)
7. washThe combined organic layers were washed with brine
8. dry with materialdried (MgSO4)
9. customThe solvent was removed
10. dissolutiona half portion of the residue was dissolved in TFA (3 mL)
11. stirringwas stirred under nitrogen at room temperature for 72 hours
12. additionThe solution was poured onto ice-water
13. customthe white precipitate obtained
14. customwas collected on a filter
15. washThe solid was washed with water
16. custompurified by a flash chromatography (methylene chloride:methanol/25:1, silica gel)

ORDレコード

ord-5508978f041c4c2aabcd76730def31de

出典データセット

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06693103B2