2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazole-3-carbaldehyde → (5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-[2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazol-3-yl]-methanol

Temperature

-20 °C

5-Chloro-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (629, 0.15 g, 0.34 mmol) was dissolved in tetrahydrofuran (3 mL, 40 mmol) and the solution was cooled to −20° C. 2 M isopropylmagnesium chloride in tetrahydrofuran (200 μL) was added dropwise and the reaction was stirred and allowed to warm to −5° C. After the reaction was cooled to −20° C., 2-ethyl-5-(4-fluoro-benzylamino)-2H-pyrazole-3-carbaldehyde (530, 0.043 g, 0.17 mmol, prepared as described in Example 47, Scheme 162, Step 5) in tetrahydrofuran (4 mL) was added to the mixture. The reaction was stirred to −5° C., then concentrated, ethyl acetate was added and the mixture was washed with sodium bicarbonate saturated solution and brine. After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure. Purification with silica gel column chromatography eluting with a gradient of ethyl acetate (5-80%) in hexanes gave the desired compound (630, 0.038 g, 40%).

1. temperatureto warm to −5° C
2. temperatureAfter the reaction was cooled to −20° C.
3. stirringThe reaction was stirred to −5° C.
4. concentrationconcentrated
5. additionethyl acetate was added
6. washthe mixture was washed with sodium bicarbonate saturated solution and brine
7. dry with materialAfter drying over anhydrous sodium sulfate
8. customthe solvent was removed under reduced pressure
9. customPurification with silica gel column chromatography
10. washeluting with a gradient of ethyl acetate (5-80%) in hexanes

ORD record

ord-7c8efe1e47e442e0a0b8feeda7b7d388

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169250B2