1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N-(3-(trifluoromethyl)benzyl)-2-(2-(2-(chloromethyl)picolinamido)-5-(piperidin-1-yl)phenyl)isonicotinamide

Participants

Reaction Conditions

Reaction Steps

Into a 50-mL 1-neck bottle, was placed a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-(piperidin-1-yl)phenyl)isonicotinamide (1.83 g, 4.03 mmol, 1.00 equiv) in dichloromethane (30 mL), 6-(chloromethyl)picolinic acid (1.04 g, 6.05 mmol, 1.50 equiv), EDC.HCl (1.54 g, 8.06 mmol, 2.00 equiv), and 4-dimethylaminopyridine (490 mg, 4.02 mmol, 1.00 equiv). The resulting solution was stirred for 4 h at 25° C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with dichloromethane:methanol (100:1). The product was obtained as 2 g (82%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 13.01 (s, 1H), 9.54 (t, J=8.7 Hz, 1H), 9.09 (d, J=5.1 Hz, 1H), 8.51 (d, J=9.0 Hz, 1H), 8.25 (s, 1H), 8.12-8.04 (m, 2H), 7.87-7.37 (m, 6H), 7.36 (s, 1H), 7.14 (dd, J=9.0 Hz, 1H), 4.95 (s, 2H), 4.65 (t, J=4.8 Hz, 2H), 3.34-3.20 (m, 4H), 1.67-1.55 (m, 6H). MS (ES, m/z): 608 [M+H]+.

Provenance & Evidence