1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-(4-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

Participants

Reaction Conditions

Reaction Steps

Into a 5-mL vial, was placed a solution of 2-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide 8d (100 mg, 0.23 mmol, 1.00 equiv) in dichloromethane (5 mL), 4-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (74 mg, 0.28 mmol, 1.20 equiv), EDC.HCl (90 mg, 0.47 mmol, 2.00 equiv), and 4-dimethylaminopyridine (43 mg, 0.35 mmol, 1.50 equiv). The resulting solution was stirred overnight at 30° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was washed with 3×10 mL of water and 1×10 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (150 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 57.8 mg (31%) of a light yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.684(d, J=9 Hz, 1H), 8.392-8.400(m, 1H), 8.179(s, 1H), 8.047-8.075(m, 3H), 7.991-7.999(m, 1H), 7.589-7.727(m, 5H), 7.078-7.087(m, 1H), 4.007(s, 2H), 3.556-3.615(m, 4H), 3.393-3.436(m, 2H), 3.171-3.263(m, 4H), 3.052-3.095(m, 2H), 2.538-2.560(m, 3H), 1.998(m, 4H), 1.788-1.804(m, 2H), 1.286-1.334(m, 6H). MS (ES, m/z): 676 [M+H]+.

Provenance & Evidence