Diisopropylethylamine → N-(4-chloro-2-(6-((3-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)phenyl)-3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamide

Participants

Reaction Conditions

Reaction Steps

Into a 50-mL round bottom flask, was placed a solution of 6-(2-amino-5-chlorophenyl)-N-(3-(trifluoromethyl)benzyl)pyrimidin-4-amine 65b (200 mg, 0.53 mmol, 1.00 equiv) in N,N-dimethylformamide (5 mL), 3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (130 mg, 0.49 mmol, 1.00 equiv), HATU (300 mg, 0.79 mmol, 1.50 equiv), and N,N-diisopropylethylamine (270 mg, 2.09 mmol, 5.00 equiv). The resulting solution was stirred for 2 days at 25° C. in an oil bath. The reaction was then quenched with 50 mL of water. The resulting solution was extracted with 2×100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×50 mL of saturated NH4Cl, dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude product (200 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 36.1 mg (9%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 8.73 (s, 1H), 8.60 (d, J=9.3 Hz, 1H), 8.41 (s, 1H), 8.19 (m, 1H), 7.92 (m, 3H), 7.64 (m, 7H), 7.14 (s, 1H), 4.73 (d, J=5.7 Hz, 2H), 3.35 (s, 2H), 3.14 (d, J=6.9 Hz, 4H), 1.18 (t, J-7.2 Hz, 6H). MS (ES, m/z): 625 [M+H]+.

Provenance & Evidence