5-(Chloromethyl)-2-methoxypyridine → HCID 86682409, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-(chloromethyl)-2-methoxypyridine (0.117 g, 0.745 mmol) in 0.3 mL of tetrahydrofuran under an atmosphere of nitrogen was added Rieke zinc (0.76 M, 0.98 mL, 0.74 mmol). The mixture was heated at 90° C. for 2 h and then cooled to 0° C. 5-Bromo-8-[(1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl]-9,9-dimethyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one (0.075 g, 0.15 mmol) and bis(tri-tert-butylphosphine)palladium(0) (2.3 mg, 0.0045 mmol) were added and the mixture was stirred at ambient temperature for 30 min. The mixture was diluted with saturated aqueous ammonium chloride and extracted 2× with dichloromethane. The combined organic extracts were washed with brine, dried with magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC followed by purification via silica gel chromatography, eluting with 0-10% methanolic ammonium hydroxide (10%) in dichloromethane, to provide 8-[(1S,2S)-2-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl]-5-[(6-methoxypyridin-3-yl)methyl]-9,9-dimethyl-8,9-dihydro-7H-pyrrolo[3,4-h]quinolin-7-one.

Provenance & Evidence