反应详情

A mixture of TFA salt of 6-piperazin-1-yl-pyridazine-3-carboxylic acid (3-methylbutyl)amide (100 mg, 0.25 mmol), 4,4,4-trifluoro-2-methylbutyric acid (47.8 mg, 0.31 mmol), 1,8-diazabicylco[5.4.0]undec-7-ene (77.8 mg, 0.51 mmol) and 1-hydroxy-benozotriazole hydrate (41.4 mg, 0.31 mmol) in DMF (2 mL) was stirred at ambient temperature for 15 minutes. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (47.6 mg, 0.31 mmol) was added to this solution. The reaction mixture was stirred at ambient temperature overnight and then diluted with ethyl acetate (50 mL) and washed with aqueous saturated NaHCO3 (2×20 mL) and finally with brine (2×20 mL). The organic extract was dried over anhydrous Na2SO4, concentrated, and then purified by column chromatography eluted with hexanes:ethyl acetate (1:2). The product was obtained as a white flaky solid (80 mg, 75% yield). 1H NMR (300 MHz, CDCl3) δ 8.07, 7.85, 7.01, 3.60-4.00, 3.50, 3.15, 2.80, 2.21, 1.70, 1.50, 1.25, 0.95. MS (ES+) m/z 416 (M+1).

1. stirringThe reaction mixture was stirred at ambient temperature overnight
2. washwashed with aqueous saturated NaHCO3 (2×20 mL) and finally with brine (2×20 mL)
3. extractionThe organic extract
4. dry with materialwas dried over anhydrous Na2SO4
5. concentrationconcentrated
6. custompurified by column chromatography
7. washeluted with hexanes:ethyl acetate (1:2)