Diisopropylethylamine → N1-(2-(2-hydroxyethoxy)ethyl)-N3-(4-(piperidin-1-yl)-2-((5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)carbamoyl)phenyl)isophthalamide

Participants

Reaction Steps

Into a 50-mL round bottom flask, was placed a solution of 3-((2-(2-hydroxyethoxy)-ethyl)carbamoyl)benzoic acid (189.3 mg, 0.75 mmol, 1.10 equiv) in N,N-dimethylformamide (2.5 mL), HATU (1034 mg, 2.72 mmol, 4.00 equiv), and N-ethyl-N-isopropylpropan-2-amine (351 mg, 2.72 mmol, 4.00 equiv). This was followed by dropwise addition of a solution of 2-amino-5-(piperidin-1-yl)-N-(5-(3-(trifluoromethyl)phenyl)-pyrazin-2-yl)benzamide (300 mg, 0.68 mmol, 1.00 equiv) in N,N-dimethylformamide (2.5 mL) with stirring. The resulting solution was stirred overnight at 40° C. in an oil bath. The resulting solution was diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 2×20 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude product was purified by reverse phase HPLC eluting with 0.05% TFA in a water/CH3CN gradient. The product was obtained as 30 mg (7%) of a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 11.45 (s, 1H), 10.95 (s, 1H), 9.46 (s, 1H), 9.22 (s, 1H), 8.67 (m, 1H), 8.38 (m, 3H), 8.01 (m, 3H), 7.80 (m, 3H), 7.77 (m, 2H), 7.63 (m, 1H), 7.48 (m, 1H), 7.25 (m, 1H), 3.52 (m, 12H), 3.29 (m, 5H), 2.98 (s, 1H), 1.69 (m, 6H). MS (ES, m/z): 677 [M+H]+.

Provenance & Evidence