反应详情

To a solution of 6-(5-amino-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one hydrochloride (intermediate A-2, 0.062 g, 0.214 mmol) in MeOH (1.5 mL) was added AcOH (0.154 g, 2.57 mmol), followed by 2-(tert-butyldimethylsilyloxy)acetaldehyde (0.039 g, 0.225 mmol) and the reaction mixture was stirred at room temperature for 1 h. Then, NaBH3CN (0.027 g, 0.428 mmol) in THF (0.6 mL) was added to the reaction mixture and stirring at room temperature was continued for 2 h. The mixture was diluted with EtOAc, poured into aq. NaHCO3 (10 mL) and the aqueous layer was extracted with EtOAc (2×25 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.06 g, 68%) as a yellow solid. MS: 412.3 (M+H+).

1. stirringstirring at room temperature
2. waitwas continued for 2 h
3. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
4. washCombined organics were washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customevaporated to dryness
8. customThe residue was purified by silica gel flash chromatography
9. washeluting with a 0 to 5% MeOH-DCM gradient