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

Participants

Reaction Conditions

Reaction Steps

Dry THF (5 ml) was added to a mixture of phenyl 6-(((tert-butyldimethylsilyl)oxy)methyl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 38, 120 mg, 0.254 mmol) and racemic 6-amino-4-(2-((dimethylamino)methyl)morpholino)nicotinonitrile (intermediate 77, 66 mg, 0.254 mmol). The resulting solution was evaporated, the flask flushed with argon, THF (1.3 ml) added and then cooled to −78° C. A solution of LHMDS in methylcyclohexane (0.9 M, 0.62 ml, 0.559 mmol) was added drop wise over 5 minutes, the reaction mixture stirred at −78° C. for a further 15 minutes then allowed to warm to 0° C. and aqueous NH4Cl (1 M) added. The mixture was extracted with DCM (3×), dried over MgSO4 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 a clear brown glass. (UPLC-MS 6) tR 1.21; ESI-MS 640.5 [M+H]+.

Provenance & Evidence