1,1'-Carbonyl-di-(1,2,4-triazole) → (racemic) 6-(1-((tert-butyldimethylsilyl)oxy)ethyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 524 mg, 2.73 mmol) in DMF (1.5 mL) was added drop wise to a cooled suspension of di(1H-1,2,4-triazol-1-yl)methanone (448 mg, 2.73 mmol) in DMF (1.5 mL) at 0° C. The reaction mixture was stirred for 3 h at 0° C., after which it was allowed to warm to room temperature. A solution of (racemic) 6-(1-((tert-butyldimethylsilyl)oxy)ethyl)-7-(dimethoxymethyl)-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 185, 500 mg, 1.364 mmol) in DMF (2.0 mL) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with MeOH (100 mL) and solid precipitates were filtered off. Solvents were concentrated and the crude material was purified by silica gel column chromatography eluting with a gradient of MeOH (0-4%) in DCM, followed by re-purification with a gradient of EtOAc (0-40%) in heptane. Fractions containing the product were combined to yield the title compound as a waxy solid. (UPLC-MS 3) tR 1.66 min, ESI-MS 585.3 [M+H]+.

Provenance & Evidence