2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde → (R)-N-(5-cyano-4-((1-methoxypropan-2-yl)oxy)pyridin-2-yl)-7-(dimethoxymethyl)-6-formyl-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridine-3-carbaldehyde (intermediate 41, 156 mg, 0.660 mmol), (R)-phenyl(5-cyano-4-((1-methoxypropan-2-yl)oxy)pyridin-2-yl)carbamate (intermediate 145, 281 mg, 0.858 mmol) and DMAP (121 mg, 0.990 mmol) in DMF (3 ml) was heated for 1 h at 90° C. The cooled reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution, extracted 2× with EtOAc, the organic layers dried over Na2SO4 and evaporated. The residue was applied to a 40 g RediSep® column and purified by normal phase chromatography, eluting with hetane and then a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound. (UPLC-MS 6) tR 1.20; ESI-MS 470.2 [M+H]+.

Provenance & Evidence