反应详情

温度

110 °C

To 1-ethyl-1H-pyrazol-5-amine (Aldrich, 1.52 g, 13.7 mmol) was added a solution of diethyl (1-chloropropylidene)propanedioate (3.21 g, 13.7 mmol) in toluene (40 mL) followed by triethylamine (3.78 mL, 27.3 mmol) and then heated at reflux for 6 h. The cooled mixture was concentrated to dryness and the resulting brown residue was treated with phosphorus oxychloride (25 mL, 0.274 mol) and heated to 110° C. for 17.5 h. The cooled mixture was concentrated to dryness and the residue was to water (caution, exotherm) and extracted with ethyl acetate. The aqueous phase was treated with aqueous sodium hydroxide (2M) to achieve pH 9 and extracted with additional ethyl acetate. The combined organics were washed with aqueous sodium bicarbonate, then brine, dried and concentrated to dryness to afford 3.6 g of a dark brown oil. The product was purified by flash chromatography on silica (150 mL) eluting with ethyl acetate/cyclohexane from 1:10 to 1:8 to afford 1.8 g of the title compound. LC-MS m/z 282 (M+H)+, 3.46 min (ret time).

1. temperatureheated
2. temperatureat reflux for 6 h
3. concentrationThe cooled mixture was concentrated to dryness
4. concentrationThe cooled mixture was concentrated to dryness
5. extractionextracted with ethyl acetate
6. additionThe aqueous phase was treated with aqueous sodium hydroxide (2M)
7. extractionextracted with additional ethyl acetate
8. washThe combined organics were washed with aqueous sodium bicarbonate
9. dry with materialbrine, dried
10. concentrationconcentrated to dryness