Tetrahydrofuran → (racemic) 7-(dimethoxymethyl)-N-(5-(1-hydroxypentyl)pyridin-2-yl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

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Reaction Steps

A solution of 6-bromo-N-(5-cyanopyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide (intermediate 2H, 50 mg, 0.116 mmol) in THF (2 ml) at −78° C. was treated with n-BuLi (1.5 M in hexane, 217 μl, 0.326 mmol) and stirred for 2 min. The reaction mixture was treated with N,N-dimethylform-13C-amide (45.6 μl, 0.578 mmol) and stirred for 0.5 h. The reaction was quenched by addition of sat. aq. NH4Cl, warmed to room temperature and extracted with EtOAc (2×). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in MeOH (2 ml) and DCM (1 ml), treated with NaBH4 (8.75 mg, 0.231 mmol) and stirred for 10 min. The reaction was quenched by addition of sat. aq. NH4Cl and extracted with EtOAc (2×). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (4 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) the product containing fractions were concentrated to give the title compound as a yellow oil. (UPLC-MS 3) tR 1.09 min; ESI-MS 415.2 [M+H]+.

Provenance & Evidence