Phosphorus oxychloride → [4-Chloro-3-methyl-1-(2-pyridinyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]phenylmethanone

Temperature

100 °C

A solution of 4-hydroxy-3-methyl-1-(2-pyridinyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (2.0 g, 7.4 mmol) in phosphorous oxychloride (19 mL, 200 mmol) was heated and stirred at 100° C. for 1.5 hours. After the solution was cooled to room temperature, the solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (50 mL) and cooled to −78° C. To the solution, a solution of phenylmagnesium bromide (1M tetrahydrofuran solution, 30 mL, 30 mmol) was added dropwise at the same temperature, and the mixture was stirred for 1 hour, and at room temperature further for 0.5 hour. The mixture was poured into an aqueous saturated ammonium chloride solution and organic matter was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Purification of the residue by silica gel chromatography (hexane:chloroform:ethyl acetate=2:1:1 to 1:1:1) gave the title compound (0.83 g, 38% yield).

1. temperatureAfter the solution was cooled to room temperature
2. customthe solvent was evaporated under reduced pressure
3. dissolutionThe residue was dissolved in tetrahydrofuran (50 mL)
4. temperaturecooled to −78° C
5. stirringthe mixture was stirred for 1 hour
6. waitat room temperature further for 0.5 hour
7. extractionwas extracted with ethyl acetate
8. washThe extract was washed with saturated brine
9. dry with materialdried over anhydrous sodium sulfate
10. customthe solvent was evaporated under reduced pressure
11. customPurification of the residue by silica gel chromatography (hexane:chloroform:ethyl acetate=2:1:1 to 1:1:1)

ORD record

ord-8c65a0d6655b4138972321d5491f356a

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06949648B2