Hydrochloric Acid → 3-[4-(1-Amino-cyclobutyl)-phenyl]-8-cyclopropyl-2-phenyl-chromen-4-one hydrochloride

Participants

Reaction Steps

Following the procedure used to prepare 3-[4-(1-amino-cyclobutyl)-phenyl]-6-fluoro-2-phenyl-chromen-4-one, a mixture containing 70% {1-[4-(8-cyclopropyl-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester and 30% {1-[4-(8-bromo-4-oxo-2-phenyl-4H-chromen-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester was treated with TFA. The resultant free base was reacted with 1-methylpyrazole-4-boronic acid pinacol ester following the procedure of (1-{4-[4-oxo-2-phenyl-7-(2H-pyrazol-3-yl)-4H-chromen-3-yl]-phenyl}-cyclobutyl)-carbamic acid tert-butyl ester. The combined products were dissolved in a mixture of MeOH (7 mL), water (7 mL) and 1 M HCl (0.6 mL) and chromatographed on a 5 g C18 cartridge {gradient 10 to 90% MeOH in water+1 M HCl (60 μL in each 10 mL of eluent)} to give the title compound as a white solid (11 mg). 1H NMR (300 MHz, DMSO-d6): δ 8.60 (s, 3H), 7.91 (dd, J=7.1 and 2.4 Hz, 1H), 7.52-7.27 (m, 11H), 2.65-2.47 (m, 4H), 2.45-2.34 (m, 1H), 2.26-2.09 (m, 1H), 1.88-1.73 (m, 1H), 1.14-1.04 (m, 2H), 0.90-0.82 (m, 2H). LCMS (Method E): RT=4.01 min, [M+H]+=408. 3-[4-(1-amino-cyclobutyl)-phenyl]-8-(1-methyl-1H-pyrazol-4-yl)-2-phenyl-chromen-4-one hydrochloride was also isolated.

Provenance & Evidence