Citric Acid → N-[2-(4-benzylpiperazin-1-yl)-2-hydroxycarbamoylethyl]-4-(2-trifluoromethylpyrazolo-[1,5-a]-pyridin-3-ylmethoxy)benzamide

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Reaction Steps

106 g (0.3 mmol) of O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate and 0.2 ml (1.2 mmol) of diisopropylethylamine are added to a solution of 190 mg (0.3 mmol) of 2-(4-benzylpiperazin-1-yl)-3-[4-(2-trifluoromethylpyrazolo[1,5-a]pyridin-3-ylmethoxy)benzoylamino]propanoic acid in 10 ml of dimethylformamide. After stirring for 20 minutes at ambient temperature, 53 mg (0.4 mmol) of O-tert-butyldimethylsilylhydroxylamine diluted in 3 ml of dimethylformamide are added. The reaction medium is stirred at ambient temperature for 18 h, then hydrolysed with 1 ml of a 5% aqueous solution of citric acid and 2 ml of water and stirred for 1 h. The mixture is then brought to pH=8 with a saturated aqueous solution of sodium hydrogen carbonate then extracted with ethyl acetate. The organic phase is washed with a saturated aqueous solution of sodium hydrogen carbonate then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated under vacuum. The crude product obtained is precipitated in a heptane/ethyl acetate mixture then filtered. The solid obtained is recrystallized in ethyl acetate. 41 mg (21%) of N-[2-(4-benzylpiperazin-1-yl)-2-hydroxycarbamoylethyl]-4-(2-trifluoromethylpyrazolo-[1,5-a]-pyridin-3-ylmethoxy)benzamide are obtained in the form of a white solid.

Provenance & Evidence