Triethylamine → 7-(Dimethoxymethyl)-6-(1-(oxetan-3-yl)piperidin-4-yl)-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, 0.94 g, 2.294 mmol), 3-oxetanone (0.777 g, 10.78 mmol) and Et3N (0.96 ml, 6.88 mmol) in 1,2-dichloroethane (50 ml) was cooled to 0° C., treated with sodium triacetoxyborohydride (1.54 g, 6.88 mmol) and then slowly warmed to room temperature. After 1.5 h, the reaction mixture was poured into H2O and evaporated to dryness. The crude material was purified by reverse phase chromatography (Reprosil C18/250×30 mm/5 um, 0.1% TFA in H2O/acetonitrile 70:30 to 5:95). The product-containing fractions were treated with NaHCO3 and then concentrated to dryness. The residue was suspended in MeOH, stirred for 1 h and filtered, washing with additional MeOH. The filtrate was evaporated to give the title compound as a yellow solid. (UPLC-MS 3) tR 0.34 min; ESI-MS 348.2 [M+H]+.

Provenance & Evidence