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With hydrogenchloride In 1,4-dioxane at 20℃; for 1h;
1.3 (third step)
At 0 to N- (1H- benzo [d] imidazole-6-yl) -8 - ({cis-4 - [(tert-butyldimethylsilyl) oxy) cyclohexyl] oxy quinazolin-2-yl} amine (4.0 g, 8.18 mmol) in 1,4-dioxane (20 ml) was added 4N-HCl / 1,4- dioxane (20 ml), and then the mixture was stirred at room temperature for one hour. The residue by distillation under reduced pressure to remove the solvent obtained, a saturated aqueous solution of sodium hydrogen carbonate (25 ml). The precipitated solid was filtered. Washed with ethyl acetate (20 mL) after use, and the precipitated solid was dried to give the title compound (2.0 g).
With hydrogenchloride In ethanol at 35 - 50℃; for 24h;
47 Example 47 Manufacturing cis -4 - ({2 - [(1H- benzo [d] imidazole-6-yl) amino] quinazolin-8-yl} oxy) cyclohexanol hydrochloride
Of the compound of Example 1 (19.3 g, 51.4 mmol), was added 0.2M hydrochloric acid - ethanol (273 ml, 51.4 mmol), and the mixture was stirred at 35-50 24 hours. After the mixture was cooled to room temperature, the precipitated product was filtered, washed with a little ethanol and dried to give the title compound (18.0 g).