Methylcyclohexane → racemic 6-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-(quinuclidin-3-yloxy)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of LHMDS in methylcyclohexane (0.9 M, 0.70 ml, 0.630 mmol) was added drop wise over 5 minutes to a mixture of phenyl 6-(((tert-butyldimethylsilyl)oxy)methyl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 38, 135 mg, 0.287 mmol) and racemic 6-amino-4-(quinuclidin-3-yloxy)nicotinonitrile (intermediate 79, 70.0 mg, 287 mmol) in THF (2.9 ml) cooled at −78° C. The reaction mixture was stirred at −78° C. for a further 10 minutes then allowed to warm to 0° C. and aqueous NH4Cl (1 M) added. The mixture was extracted with DCM (3×), dried over Na2SO4 and evaporated. The residue was applied to a 4 g RediSep® silica column as a DCM solution and purified by normal phase chromatography, eluting with a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as an off-white solid. (UPLC-MS 6) tR 1.27; ESI-MS 623.3 [M+H]+.

Provenance & Evidence