Triethylamine → (+/-)-3-benzyl-7-chloro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-4,4-dimethyl-4,5 dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-quinazolin-4-one

To a solution of (±)-2-[1-(2-amino-2-methyl-propylamino)-2-methyl-propyl]-3-benzyl-7-chloro-3H-quinazolin-4-one (250 mg, 0.61 mmol) in dichloromethane (10 mL) was added triethylamine (295 μL, 2.12 mmol), followed by 4-fluoro-3-methylbenzoyl chloride (105 mg, 0.61 mmol). The resultant solution was stirred at ambient temperature for 2 hours, then evaporated under reduced pressure to a crude white solid. The resultant solid was treated with glacial acetic acid (10 mL) then the resultant suspention was heated at reflux for 48 hours. The reaction was cooled to ambient temperature then evaporated under reduced pressure to a crude oil. The oil was quenched with saturated aqueous sodium bicarbonate (10 mL) and brine (5 mL). The aqueous layer was extracted with dichloromethane (2×5 mL) and the combined extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (5–10% ethyl acetate/hexanes) to furnish (±)-3-benzyl-7-chloro-2-{1-[2-(4-fluoro-3-methyl-phenyl)-4,4-dimethyl-4,5-dihydro-imidazol-1-yl]-2-methyl-propyl}-3H-quinazolin-4-one (138 mg, 43%) as a white solid: LCMS 531 (M++H)

1. customevaporated under reduced pressure to a crude white solid
2. additionThe resultant solid was treated with glacial acetic acid (10 mL)
3. temperaturethe resultant suspention was heated
4. temperatureat reflux for 48 hours
5. customthen evaporated under reduced pressure to a crude oil
6. customThe oil was quenched with saturated aqueous sodium bicarbonate (10 mL) and brine (5 mL)
7. extractionThe aqueous layer was extracted with dichloromethane (2×5 mL)
8. dry with materialthe combined extracts were dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel chromatography (5–10% ethyl acetate/hexanes)

ORD 기록

ord-9c1404198f3a4f81aee76601ec24ac3e

출처 데이터셋

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07214800B2