2-Amino-5-methylpyridine → HCID 57504320, compound

Participants

Reaction Steps

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (333 mg, 0.88 mmol) was added to (2S)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-isopropoxypropanoic acid D2 (300 mg, 0.80 mmol), 5-methylpyridin-2-amine (95 mg, 0.88 mmol) and N-ethyldiisopropylamine (0.153 mL, 0.88 mmol) in DCM (15 mL) at room temperature under nitrogen. The resulting solution was stirred at room temperature for 24 hours. The reaction mixture was diluted with DCM (25 mL) and washed with saturated brine (20 mL). The aqueous layer was re-extracted with DCM (30 mL). The combined organics were evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (2S)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-isopropoxy-N-(5-methylpyridin-2-yl)propanamide (175 mg, 47.1%), 10% ee. 143 mg of this material was further purified by chiral preparative HPLC on Chiralcel OJ (50 mm×20 μm), eluent isohexane/EtOH/MeOH 70/15/15 to afford (2S)-2-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-isopropoxy-N-(5-methylpyridin-2-yl)propanamide (56 mg, >99% ee which eluted after the R enantiomer).

Provenance & Evidence