反应详情

To a 50 mL dry three-necked flask, 0.554 g (0.002 mol) of self-made 2-[4-(3,6-dichloro-pyridazin-4-yl)-piperazin-1-yl]-ethanol, 0.28 g (0.002 mol) of 6-hydroxy-nicotinic acid ethyl ester, 0.612 g of triphenylphosphine were added, 15 mL of anhydrous tetrahydrofuran was poured into the flask under condition of ice bath and nitrogen gas protection, then 0.35 mL of diethyl azodiformate (DEAD) dissolved in 5 mL of anhydrous tetrahydrofuran was added dropwise into the flask, after the dropwise addition, the temperature was elevated to room temperature, the agitation was kept overnight. The solvent was removed by evaporation using a rotation evaporator next day, the residue was poured into 100 mL of water, extracted for three times using total 150 mL of dichloromethane, the extract solutions were combined together, dried over anhydrous Na2SO4, concentrated, and separated by column chromatograph (eluent, petroleum ether:ethyl acetate:methanol=10:5:0.15) to obtain 0.32 g of 4-{2-[4-(3,6-dichloro-pyridazin-4-yl)-piperazin-1-yl]-ethoxy}-phenylacetic acid methyl ester, a white solid. Yield: 42.3%, m.p. 140˜141° C. 1H-NMR (400MHz, CDCl3) δppm: 1.37˜1.41(t, 3H, J=7.3Hz), 2.79(brs, 4H), 2.91(brs, 2H), 3.36(brs, 4H), 4.35˜4.40(q, 2H, J=7.3Hz), 4.57(brs, 2H), 6.78˜6.80(d, 2H, J=8.7Hz), 6.86(s, 1H), 8.16˜8.18(dd, 1H, J1=8.7Hz, J2=2.2Hz).

1. additionwas added dropwise into the flask
2. additionafter the dropwise addition
3. customwas elevated to room temperature
4. customThe solvent was removed by evaporation
5. customa rotation evaporator next day
6. additionthe residue was poured into 100 mL of water
7. extractionextracted for three times
8. dry with materialdried over anhydrous Na2SO4
9. concentrationconcentrated
10. customseparated by column chromatograph (eluent, petroleum ether:ethyl acetate:methanol=10:5:0.15)