Hydrochloric Acid → 2-(2-methoxyethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-2H-pyrazolo[3,4-c][1,8]naphthyridin-4-amine

Participants

Reaction Conditions

Reaction Steps

Hydrochloric acid (10 mL of 1M) was added to a solution of 2-tert-butoxycarbonylamino-3-pyridylboronic acid (2.59 g, 10.9 mmol), and the resulting mixture was heated at 80° C. for 45 minutes and allowed to cool to room temperature. Potassium carbonate (3.60 g, 26.0 mmol) was added with stirring, and then DME (20 mL), 4-bromo-1-(2-methoxyethyl)-5-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazole-3-carbonitrile (1.75 g, 5.33 mmol), and dichlorobis(triphenylphosphine)palladium(II) (190 mg, 0.27 mmol) were added. The reaction was carried out as described in Part C of Example 4. The crude product was purified by automated flash chromatography (eluting with 0% to 35% CMA in chloroform) followed by recrystallization from acetonitrile (30 mL) after hot filtration. The crystals were washed with cold acetonitrile and dried overnight in a vacuum oven at 60° C. to provide 0.13 g of 2-(2-methoxyethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-2H-pyrazolo[3,4-c][1,8]naphthyridin-4-amine as light yellow needles, mp 230-233° C.

Provenance & Evidence