3-Methylpyridine → 3,4,5trimethoxy-4-(1H-pyrrolo[2,3-b]pyridin-2-yl)phenol

Temperature

2.5 °C

33 ml of lithium diisopropylamide solution (1 M in THF) are initially introduced at 0° C. under nitrogen, and a solution of 3.6 g of 3-methylpyridine 1 in 50 ml of THF is added dropwise with stirring at 0-5° C. The mixture is stirred for a further 30 minutes at the temperature indicated, and a solution of 5 g of 3,4,5-trimethoxybenzonitrile in 50 ml of THF is subsequently added. The mixture is stirred at 0-5° C. for a further 1.5 h, and finally a further 33 ml of lithium diisopropylamide solution are added. The reaction mixture is subsequently warmed at 80° C. for 2 h. For work-up, the batch is allowed to cool to room temperature, and the mixture is poured onto ice. After phase separation, the mixture is extracted a further three times with 100 ml of dichloromethane each time, the combined organic phases are dried, and the solvent is removed in vacuo. The residue is purified by chromatography over a silica-gel column using ethyl acetate, giving 4.3 g of yellow crystals, which exhibit a melting point of 174.0-175.5° C.

1. stirringThe mixture is stirred for a further 30 minutes at the temperature
2. stirringThe mixture is stirred at 0-5° C. for a further 1.5 h
3. temperatureThe reaction mixture is subsequently warmed at 80° C. for 2 h
4. temperatureto cool to room temperature
5. additionthe mixture is poured onto ice
6. customAfter phase separation
7. extractionthe mixture is extracted a further three times with 100 ml of dichloromethane each time
8. customthe combined organic phases are dried
9. customthe solvent is removed in vacuo
10. customThe residue is purified by chromatography over a silica-gel column

ORD record

ord-c3ee4249e0664abdac89f159eabd06ad

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859581B2