Sodium Hydroxide → 8-{4-[4-(1-Benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzyl}-8-aza-bicyclo[3.2.1]octan-3-ol

참여 물질

반응 단계

To a solution of CHCl3 (1.5 mL) and MeOH (3 mL) in a round-bottom flask under N2 was added 8-aza-bicyclo[3.2.1]octan-3-ol 24 (70 mg, 0.495 mmol). AcOH was added to adjust the pH to 5. To the amine solution was added 4-[4-(1-benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzaldehyde 22 (100 mg, 0.198 mmol) and the resulting solution was stirred at room temperature for 3 hours. NaCNBH3 was added to the reaction mixture which was then allowed to stir overnight at room temperature under an atmosphere of N2. The solution was diluted with CH2Cl2 and poured into 1N NaOH (10 mL). The aqueous layer was separated and extracted with another 2×15 mL of CH2Cl2. The organic layers were dried (MgSO4) and the solvent was removed under reduced pressure to provide a yellow viscous oil. The residue was purified by flash chromatography (silica gel, CH2Cl2-10% MeOH/CH2Cl2) to provide 45 mg of compound 23 as a white solid in 36% yield. HPLC, rt=5.25 min; MS (Cl) m/e 616.2 (M++1, 100).

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