Hydrochloric Acid → Cxd-101

Participants

Reaction Conditions

Reaction Steps

tert-Butyl (2-{[4-(1-{1,3-dimethyl-1H-pyrazol-4-ylmethyl}piperidin-4-yl)benzoyl]amino}phenyl)carbamate (prepared as described in Method 6 below; 7.61 g, 15.11 mmol) was dissolved in 1,4 dioxane (70 ml) and cooled to 0° C., using an ice—water bath. A 4M solution of hydrogen chloride in 1,4 dioxane (150 ml, 600 mmol) was then added slowly. The resultant suspension was allowed to warm to room temperature and lumps broken up by agitation with a glass rod. The reaction mixture was stirred at room temperature for 18 hours. The mixture was filtered, under suction. The solid obtained was dissolved in water (200 ml), and the solution adjusted to pH 12 by slow addition of a 2M aqueous solution of sodium hydroxide. The mixture obtained was extracted with dichloromethane (300 ml) and the organics separated. The aqueous phase was further extracted with dichloromethane (200 ml) and the combined extracts washed with brine, dried over magnesium sulphate, filtered and evaporated to give a clear gum. The gum was taken up in diethyl ether and re-evaporated to dryness to afford the title compound (5.69 g, 93%); NMR Spectrum (CDCl3) δ 1.81 (m, 4H), 2.07 (m, 2H), 2.25 (s, 3H), 2.56 (m, 1H), 3.04 (m, 2H), 3.39 (s, 2H), 3.81 (s, 3H), 3.85 (s, 2H), 6.84 (m, 2H), 7.08 (m, 1H), 7.24 (s, 1H), 7.33 (m, 3H), 7.82 (m, 3H). Mass Spectrum: M+H+ 404.

Provenance & Evidence