Potassium Carbonate → 6-(1-(2,2-Difluoroethyl)piperidin-4-yl)-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine

Participants

Reaction Conditions

Reaction Steps

A mixture of 7-(dimethoxymethyl)-6-(piperidin-4-yl)-1,2,3,4-tetrahydro-1,8-naphthyridine hydrochloride (Intermediate 342, 0.78 g, 2.14 mmol), 1,1-difluoro-2-iodoethane (0.63 g, 3.22 mmol) and K2CO3 (0.89 g, 6.43 mmol) in DMF (20 ml) was stirred at 70° C. After 16 h, the reaction mixture was cooled to room temperature, diluted with H2O and extracted with EtOAc (3×). The combined organic phases were washed with brine, dried over Na2SO4 and evaporated. The crude material was purified by reverse phase chromatography (Reprosil C18/250×30 mm/5 um, 35 ml/min, 0.1% TFA in H2O/acetonitrile 95:5 to 40:60 in 25 min, then to 5:95 in 1 min). The product-containing fractions were treated with NaHCO3 and then concentrated to remove acetonitrile. The watery residue was diluted with H2O and extracted with EtOAc (2×). The combined organic phases were dried over Na2SO4 and evaporated to give the title compound as a yellow solid. (UPLC-MS 3) tR 0.41; ESI-MS 356.2 [M+H]+.

Provenance & Evidence