Tetrabutylammonium Fluoride → (2S)-2-(1-(3-cyano-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)-3-(2-hydroxyethoxy)propanamide

Tetrabutylammonium fluoride (1M in THF) (0.346 mL, 0.35 mmol) was added to (2S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-(1-(3-cyano-2-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-N-(5-cyanopyridin-2-yl)propanamide (Intermediate AT1) (250 mg, 0.35 mmol) in THF (2 mL) under nitrogen. The resulting mixture was stirred at ambient temperature for 90 minutes. The reaction mixture was quenched with saturated NH4Cl, diluted with DCM and poured onto a phase separator. The organic layer was evaporated to a gum. The crude product was purified by flash silica chromatography, elution gradient 50 to 100% EtOAc in isohexane to afford the product (69.0 mg, 41.2%, 92% ee). 1H NMR (400 MHz, CDCl3) δ 2.37-2.44 (4H, m), 3.73-3.86 (4H, m), 4.15-4.26 (2H, m), 6.07 (1H, t), 7.49 (1H, t), 7.63-7.68 (1H, m), 7.77-7.82 (1H, m), 7.94-8.00 (1H, m), 8.34-8.38 (1H, m), 8.43 (1H, s), 8.55-8.60 (2H, m), 9.34 (1H, s); m/z (ES−) (M−H)−=483.52; HPLC tR=1.95 min.

1. customThe reaction mixture was quenched with saturated NH4Cl
2. additiondiluted with DCM
3. additionpoured onto a phase separator
4. customThe organic layer was evaporated to a gum
5. customThe crude product was purified by flash silica chromatography, elution gradient 50 to 100% EtOAc in isohexane
6. customto afford the product (69.0 mg, 41.2%, 92% ee)

ORD record

ord-f5268c50b8f448bda657280160ca8f70

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143263B2