反应详情

温度

50 °C

210 mg (1.5 mmol) of 1-hydroxybenzotriazole and 290 mg (1.5 mmol) of 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride are added to a solution of 260 mg (1.9 mmol) of 4-but-2-ynyloxybenzoic acid (prepared as described in example 1-5) in 10 ml of dimethylformamide. The reaction medium is stirred for 15 minutes and a mixture of 420 mg (1.4 mmol) of methyl (S)-3-amino-2-(4-methanesulphonylpiperazin-1-yl)propanoate hydrochloride and 390 mg (2.8 mmol) of triethylamine in 3 ml of dimethylformamide are added. The reaction medium is stirred at ambient temperature for 1 h 30 min, heated to 50° C., over 1 h 30 min then hydrolysed with a saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic phase is washed with an aqueous solution of sodium hydrogen carbonate then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated. The crude product obtained is purified by chromatography over silica gel eluted with a 98/2 dichloromethane/methanol mixture. 620 mg (100%) of methyl (S)-3-(4-but-2-ynyloxybenzoylamino)-2-(4-methanesulphonylpiperazin-1-yl)propanoate are obtained in the form of a colourless oil.

1. additionare added
2. stirringThe reaction medium is stirred at ambient temperature for 1 h 30 min
3. extractionextracted with ethyl acetate
4. washThe organic phase is washed with an aqueous solution of sodium hydrogen carbonate
5. dry with materialwith a saturated aqueous solution of sodium chloride, dried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product obtained
9. customis purified by chromatography over silica gel
10. washeluted with a 98/2 dichloromethane/methanol mixture