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

温度

0 °C

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.

1. customwas recooled to −78° C
2. customthe resulting reaction mixture
3. temperatureto warm to room temperature
4. stirringwas stirred for 18 hours
5. extractionthe mixture extracted with ethyl acetate (2×50 mL)
6. dry with materialThe combined organic extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by column chromatography on silica gel Biotage 25S
10. washeluting with 0-100% ethyl acetate/hexane

ORDレコード

ord-57a9ef94bceb43f7aed2890b1620bf27

出典データセット

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08273749B2