Ethylene Glycol → HCID 66584734, compound

Participants

Reaction Steps

A stirred solution of 3-(6-fluoroquinolin-3-yl)-5-[1-(tetrahydro-2H-pyran-4-ylamino)ethyl]-N,N-bis{[2-(trimethylsilyl)ethoxy]methyl}pyrazolo[1,5-a]pyrimidin-7-amine (890 mg, 1.33 mmol) in dioxane (4 mL) was treated with 4 M HCl in dioxane (4 mL) followed by 1,2-ethanediol (4 mL), and the resulting amber mixture was stirred at room temperature for 15 min and then at 50° C. for 5 h at which point the reaction was near completion. The mixture was cooled to room temperature, added carefully in portions to saturated aqueous NaHCO3 (200 mL) with stirring, and extracted with DCM (3×100 mL). The combined organic phase was washed with water (100 mL) and brine (50 mL), dried over Na2SO4 and concentrated under reduced pressure. The solid residue was taken up in 10% MeOH/DCM (˜7-8 mL), diluted with diethyl ether (˜40 mL) and the small amount of precipitate that formed was removed by filtration through a fine frit. The filtrate was concentrated under reduced pressure to give 3-(6-fluoroquinolin-3-yl)-5-(1-(tetrahydro-2H-pyran-4-ylamino)ethyl)pyrazolo[1,5-a]pyrimidin-7-amine (510 mg, 80% yield @ 85% purity) as a tan amorphous solid. MS (ESI+) for C22H23FN6O m/z 407 (MAI); HPLC, 2.43 min (Method B).

Provenance & Evidence