Hydrochloric Acid → N-(2-Aminophenyl)-4-[1-(1H-pyrazol-3-ylmethyl)piperidin-4-yl]benzamide

Participants

Reaction Steps

tert-Butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate (prepared as described in Method 1 below; 200 mg, 0.51 mmol) and 1H-pyrazole-3-carbaldehyde (50.7 mg, 0.53 mmol) were stirred at ambient temperature in dichloromethane (5 ml) for 1 hour. Sodium triacetoxyborohydride (150 mg, 0.71 mmol) was added and the mixture stirred at ambient temperature for 48 hours. The resulting solution was absorbed onto an SCX-2 column, which was washed with methanol (2 column volumes) and then the product eluted with a 2M solution of ammonia in methanol (2 column volumes) to give a foam. This was dissolved in 1,4-dioxane (2 ml), a 4M solution of hydrogen chloride in 1,4-dioxane (2 ml) was added and the solution stiffed at ambient temperature for 48 hours. The product was filtered and washed with diethyl ether and air-dried. The resulting solid was dissolved in water, basified with 2N sodium hydroxide and the resulting solid filtered, washed with water and dried under vacuum to give the title compound (61 mg, 44%). NMR Spectrum: 1H NMR (DMSO d6) δ 1.71 (m, 4H), 2.07 (m, 2H), 2.56 (m, 1H), 2.95 (m, 2H), 3.53 (s, 2H), 4.86 (s, 2H), 6.16 (s, 1H), 6.60 (m, 1H), 6.78 (d, 1H), 6.97 (t, 1H), 7.18 (d, 1H), 7.37 (d, 2H), 7.64 (m, 1H), 7.91 (d, 2H), 9.55 (s, 1H), 12.59 (m, 1H); Mass Spectrum: M+H+ 376.

Provenance & Evidence