1,1'-Carbonyl-di-(1,2,4-triazole) → 6-(2-oxa-5-azaspiro[3.4]octan-5-ylmethyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Participants

Reaction Steps

A solution of di(1H-1,2,4-triazol-1-yl)methanone (320 mg, 1.95 mmol) in DMF (7 ml) was added to a mixture of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 375 mg, 1.95 mmol) in anhydrous DMF (1.5 ml) at 0° C. After stirring for 2.5 h at room temperature a solution of 5-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-2-oxa-5-azaspiro[3.4]octane (intermediate 230C, 260 mg, 0.78 mmol) in DMF (3 ml) was added. The reaction mixture was stirred for 17.5 h at room temperature, then partitioned between saturated aqueous NaHCO3 solution and EtOAc, the EtOAc phase washed with brine, dried over MgSO4 and evaporated. The residue was applied to a silica column and purified by normal phase chromatography, eluting with EtOAc then a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as a pale yellow solid. (UPLC-MS 3) Rt=0.92 min; MS m/z [M+H]+ 552.

Provenance & Evidence