反应详情

温度

80 °C

To 6-chloropyridazine-3-carboxylic acid (3-methylbutyl)amide (0.140 g, 0.610 mmol) in DMF (7 mL) was added piperidin-4-ylcarbamic acid tert-butyl ester (0.146 g, 0.730 mmol), followed by the addition of 1,8-diazabicyclo[5,4,0]undec-7-ene (0.280 mL, 1.84 mmol) and tetra-n-butylammonium iodide (6 mg). The reaction mixture was stirred at 80° C. for 16 hours. The solvent was removed in vacuo. The residue was dissolved in ethyl acetate, then washed with citric acid, sodium bicarbonate and brine solution. The organic layer was separated, and dried over anhydrous Na2SO4, and evaporated. The residue was purified by column chromatography and then treated with trifluoroacetic acid. The title compound was obtained as a white powder in 50% yield (0.090 g). 1H NMR (300 MHz, DMSO-d6) δ 8.75-8.77 (m, 1H), 7.79 (d, J=9.6 Hz, 1H), 7.34 (d, J=9.6 Hz, 1H), 4.29-4.35 (m, 2H), 3.29-3.22 (m, 1H), 3.06-3.12 (m, 1H), 2.85-2.87 (m, 1H), 2.50 (m, 1H), 1.77-1.80 (m, 2H), 1.56-1.64 (m, 4H), 1.40-1.44 (m, 2H), 1.17-1.25 (m, 1H), 0.90 (d, J=6.6 Hz, 6H).

1. customThe solvent was removed in vacuo
2. dissolutionThe residue was dissolved in ethyl acetate
3. washwashed with citric acid, sodium bicarbonate and brine solution
4. customThe organic layer was separated
5. dry with materialdried over anhydrous Na2SO4
6. customevaporated
7. customThe residue was purified by column chromatography
8. additiontreated with trifluoroacetic acid