N,N'-Dimethylethylenediamine → 3-methyl-3-(pyrimidin-5-ylmethyl)-1,3-dihydro-2H-indol-2-one

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Reaction Conditions

Reaction Steps

Pyrimidin-5-ylmethanol (510 mg, 4.63 mmol) in tetrahydrofuran (8 mL) at room temperature was treated with sodium hydride (185 mg, 4.63 mmol) and stirred for 5 minutes. p-Toluenesulfonyl chloride (883 mg, 4.63 mmol) was added, and the resulting mixture stirred for one hour to form pyrimidin-5-ylmethyl 4-methylbenzenesulfonate. In a separate flask 3-methyloxindole (682 mg, 4.63 mmol) and N,N′-dimethylethylenediamine (1.538 mL, 10.19 mmol) in tetrahydrofuran (16 mL) were cooled to −78° C. and treated dropwise with n-butyllithium (2.5M in hexanes, 4.08 mL, 10.2 mmol). The mixture was allowed to warm to 0° C. and stirred for 15 minutes. The mixture was recooled to −78° C. To this mixture was added the tetrahydrofuran solution of pyrimidin-5-ylmethyl 4-methylbenzenesulfonate via cannula; the resulting reaction mixture was allowed to warm to room temperature and was stirred for 18 hours. Water (50 mL) was added, and the mixture extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel Biotage 25S, eluting with 0-100% ethyl acetate/hexane to afford 3-methyl-3-(pyrimidin-5-ylmethyl)-1,3-dihydro-2H-indol-2-one as a white solid.

Provenance & Evidence