反应详情

[4-({[5-Fluoro-2-(4-fluoro-phenoxy)-pyridine-3-carbonyl]-amino}-methyl)-benzyl]-carbamic acid tert-butyl ester (1.62 g, 3.44 mmol) (see Preparation 5) was dissolved in a 2.25 M solution of hydrochloric acid in methanol (100 ml) and the mixture stirred at room temperature under an atmosphere of nitrogen for 4 hours before removing the solvent in vacuo. The residue was dissolved in water (50 ml), the pH adjusted to pH higher than 8 by addition of sodium hydrogen carbonate and extracted with dichloromethane (3-fold 50 ml). The combined organic extracts were dried over anhydrous magnesium sulphate and concentrated in vacuo to give N-(4-aminomethyl-benzyl)-5-fluoro-2-(4-fluoro-phenoxy)-nicotinamide hydrochloride (1.25 mg) as a gum.

1. custombefore removing the solvent in vacuo
2. dissolutionThe residue was dissolved in water (50 ml)
3. additionto pH higher than 8 by addition of sodium hydrogen carbonate
4. extractionextracted with dichloromethane (3-fold 50 ml)
5. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulphate
6. concentrationconcentrated in vacuo