Hexane → 6-((2S)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-isopropoxypropanamido)-N,N-dimethylnicotinamide

Participants

Reaction Conditions

Reaction Steps

Trimethylaluminium (2M in hexane, 0.376 mL, 0.75 mmol) was added to 6-amino-N,N-dimethylnicotinamide (CAS no. 827588-33-0) (108 mg, 0.65 mmol) in toluene (20 mL) at 0° C. under Nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (2S)-Methyl 2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-isopropoxypropanoate (Intermediate L1) (256 mg, 0.65 mmol) in toluene (6 mL) was added dropwise at this temperature. After the addition was complete, the solution was allowed to warm to ambient temperature and was then heated to reflux for 16 hours. Allowed to cool to ambient temperature. The reaction mixture was concentrated and diluted with EtOAc (100 mL) and washed with saturated brine (50 mL). The organic layer was dried (MgSO4), filtered and evaporated. 2M Trimethylaluminium in hexane (0.376 mL, 0.75 mmol) was added to 6-amino-N,N-dimethylnicotinamide (108 mg, 0.65 mmol) in toluene (20 mL) at 0° C. under Nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. The residue from the above evaporation was dissolved in toluene (6 mL) and added dropwise. After the addition was complete, the solution was allowed to warm to ambient temperature and was then heated to reflux for 16 hours. Allowed to cool to ambient temperature. The reaction mixture was concentrated and diluted with EtOAc (100 mL) and washed with saturated brine (50 mL). The organic layer was dried (MgSO4), filtered and evaporated to afford crude product.

Provenance & Evidence