Hydrochloric Acid → (αR)-6-Methoxy-α-[[4-[[(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)methyl]amino]-1-piperidinyl]methyl]-4-quinolinemethanol

Participants

Reaction Steps

To a stirred solution of the mono hydrochloride salt of (R)-2-(4-aminopiperidin-1-yl)-1-(6-methoxyquinolin-4-yl) ethanol (1d) (0.34 g, 1.0 mmole) in CH2Cl2 (25 mL) and dry ethanol (10 mL) at RT was added 5,6,7,8-tetrahydro[1,8]naphthyridine-2-carboxaldehyde (prepared according to the procedure of WO 98/08840, 0.17 g, 1.0 mmole), triethylamine (0.10 g, 1.0 mmole), and granular Na2SO4 (approximately 200 mg). After 36 h, the reaction was filtered through a sintered-glass funnel and the filtrate was concentrated. The remaining residue was dissolved in dry ethanol and reacted with NaBH4 (0.04 g, 1.0 mmole). After 12 h at RT, the reaction was concentrated under vacuum and the residue was dissolved in a mixture of H2O (2 mL) and saturated aqueous NaHCO3 (10 mL). The aqueous solution was extracted with EtOAc (2×50 mL) and the combined organic phases were washed with brine then were dried over Na2SO4. Flash chromatography on silica gel (9:1 CHCl3/MeOH containing 5% NH4OH) afforded the title compound (0.31 g, 69%) as a white solid:

Provenance & Evidence