1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N1-Methyl-N1-(2-morpholinoethyl)-N3-(4-(piperidin-1-yl)-2-((1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)carbamoyl)phenyl)isophthalamide

Participants

Reaction Conditions

Reaction Steps

Into a 50-mL round bottom flask, was placed 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), 3-(methyl(2-morpholinoethyl)carbamoyl)benzoic acid (130 mg, 0.45 mmol, 1.91 equiv), EDC.HCl (67 mg, 0.35 mmol, 1.50 equiv), 4-dimethylaminopyridine (43 mg, 0.35 mmol, 1.51 equiv), and dichloromethane (5 mL). The resulting solution was stirred for 4 h at 25° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was washed with 3×10 mL of water and 3×10 mL of aqueous NH4Cl. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 108.6 mg (66%) of a white solid. 1H-NMR (400 MHz, CD3OD, ppm): δ 8.66-8.64 (d, J=8.8 Hz, 1H), 8.39 (s, 1H), 8.16 (s, 3H), 8.07-8.05 (d, J=7.6 Hz, 1H), 7.99 (s, 1H), 7.79 (s, 1H), 7.16-7.68 (m, 3H), 7.61 (s, 1H), 7.07 (s, 1H), 4.11-4.10 (d, J=3.2 Hz, 2H), 3.98 (s, 3H), 3.80-3.77 (m, 4H), 3.59-3.54 (m, 6H), 3.14 (m, 4H), 1.99-1.79 (m, 6H). MS (ES, m/z): 704 [M+H]+.

Provenance & Evidence