反应详情

温度

100 °C

Metal sodium (35 mg) was added to methanol (1.5 mL) to prepare a solution, and the solution was concentrated under reduced pressure, followed by addition of THF (1.5 mL). This suspension was added to a solution of 2,4-dichloroquinazoline (0.30 g) in THF (1.5 mL), and the mixture was stirred at room temperature for 2 h. To the reaction mixture was added saturated brine, the mixture was extracted with chloroform, and the organic layer was dried with anhydrous magnesium sulfate. The desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and then the residue was purified by silica gel column chromatography (hexane/ethyl acetate=9:1) to obtain 2-chloro-4-methoxyquinazoline (0.27 g). (2) A mixture of 2-chloro-4-methoxyquinazoline (0.25 g), 1-((S)-3-aminopyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone mono hydrochloride (0.42 g), triethylamine (0.33 g), and THF (3.2 mL) was heated at 100° C. in a microwave reaction apparatus for 3 h. The reaction mixture was diluted with chloroform, washed with 1 M aqueous sodium hydroxide, and then dried with anhydrous magnesium sulfate. The desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and then the residue was purified by silica gel column chromatography (chloroform-chloroform/methanol=95:5, and silica gel, hexane/ethyl acetate=1:2−ethyl acetate) to obtain the title compound (37 mg).

1. washwashed with 1 M aqueous sodium hydroxide
2. dry with materialdried with anhydrous magnesium sulfate
3. customThe desiccant was removed by filtration
4. concentrationthe filtrate was concentrated under reduced pressure
5. customthe residue was purified by silica gel column chromatography (chloroform-chloroform/methanol=95:5, and silica gel, hexane/ethyl acetate=1:2−ethyl acetate)