Sodium hydride → 3-bromo-5-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine

Temperature

0 °C

NaH (0.165 g, 4.11 mmol, 60% suspension in mineral oil) was added portionwise to a cold (0° C.) solution of 3-bromo-5-nitro-1H-pyrazolo[3,4-b]pyridine (0.5 g, 2.06 mmol) in dry DMF (20 mL). The reaction mixture was stirred at 0° C. for 10 minutes, and 2-(trimethylsilyl)ethoxymethyl chloride (0.617 mL, 3.50 mmol) was added dropwise via a syringe. The cold bath was removed, and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was placed in an ice bath, diluted with ethyl acetate (400 mL) and carefully quenched with water (50 mL). The aqueous layer was separated and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried, filtered and concentrated. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (20:1) to give 3-bromo-5-nitro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-b]pyridine (0.636 g, 83%) as a solid.

1. customThe cold bath was removed
2. stirringthe reaction mixture was stirred at room temperature for 1 hour
3. customThe reaction mixture was placed in an ice bath
4. additiondiluted with ethyl acetate (400 mL)
5. customcarefully quenched with water (50 mL)
6. customThe aqueous layer was separated
7. extractionextracted with ethyl acetate (3×50 mL)
8. customThe combined organic layers were dried
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by column chromatography
12. washeluting with hexanes/ethyl acetate (20:1)

ORD record

ord-7eb26d8e903649d0beda4c90341c0c50

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394795B2