1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-bromo-N-{4-((7-chloroquinolin-4-yl)amino)cyclohexyl}-5-fluorobenzamide

Participants

Reaction Steps

A mixture of 23A cis-N,N′-bis(7-chloroquinolin-4-yl)cyclohexane-1,4-diamine (500 mg, 3.6 mmol), 3-bromo-5-fluorobenzoic acid (600 mg, 5.4 mmol), 1-hydroxybenzotriazole (245 mg, 3.6 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide(348 mg, 3.6 mmol) in 30 mL dichloromethane was stirred for 3 hours. The reaction was incomplete. 3-bromo-5-fluorobenzoic acid (160 mg, 0.9 mmol), 1-hydroxybenzotriazole (61 mg, 0.9 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (87 mg, 0.9 mmol) was added and the solution was allowed to stir overnight. The solution was then washed with 1N NaOH, dried (Na2SO4), and concentrated. The residue was purified by flash chromatography (10% methanol in dichloromethane) to provide 700 mg of pure compound, an 81% yield. MS (ESI(+)Q1MS m/z 477 (M+2 H)+; 1H NMR (300 MHz, MeOH) δ ppm 8.36-8.42 (m, 3 H), 7.95 (t, 1 H), 7.69-7.79 (m, 3 H), 7.45 (dd, 1 H), 6.83 (d, 1 H), 6.54 (d, 1 H), 3.95 (m, 1 H), 3.68 (m, 1 H), 1.66-1.98 (m, 8 H).

Provenance & Evidence