Cyclobutanone → HCID 11842670, compound

Participants

Reaction Conditions

Reaction Steps

A solution of di(tert-butyl) 1-methyl-2-propyl-2H-pyrazolo[3,4-c]quinolin-4-ylimidodicarbonate (1.32 g, 3.00 mmol) in anhydrous tetrahydrofuran (THF) (30 mL) was cooled to −78° C. under an argon atmosphere. tert-Butyllithium (7.06 mL of a 1.7 M solution in pentane) was added over a period of eight minutes, and the resulting dark-colored solution was stirred at −78° C. for 40 minutes. Cyclobutanone (1.05 g, 15 mmol) was added over a period of two minutes, and the −78° C. bath was replaced with a 0° C. bath. The reaction mixture was stirred for 10 minutes, and then saturated aqueous ammonium chloride (30 mL) was added. The aqueous layer was separated and extracted three times with tert-butyl methyl ether, and the combined organic fractions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (1.3 g) was purified by automated flash chromatography and then boiled in 2 M hydrochloric acid for 30 minutes. The solution was allowed to cool to room temperature overnight and then made basic with the addition of 2 M aqueous sodium carbonate. The resulting solution was extracted four times with chloroform, and the combined extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue (1.2 g) was purified twice by automated flash chromatography and recrystallized from acetonitrile to provide 297 mg of 1-[(4-amino-2-propyl-2H-pyrazolo[3,4-c]quinolin-1-yl)methyl]cyclobutanol as a white solid, mp 191-193° C.

Provenance & Evidence