1,1'-Carbonyl-di-(1,2,4-triazole) → HCID 118036869, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 629 mg, 3.271 mmol) in anhydrous DMF (5 ml) was added drop wise to a mixture of di(1H-1,2,4-triazol-1-yl)methanone (596 mg, 2.86 mmol) and DMF (5 ml) cooled at 0° C. After stirring for 1 h at 0° C. the reaction mixture was allowed to warm to room temperature and a solution of 3-(2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)oxazolidin-2-one (intermediate 335, 685 mg, 1.635 mmol) in DMF (5 ml) was added. The suspension was allowed to warm to room temperature, was continued to stir for 18 h and quenched by the addition of MeOH. The reaction mixture was diluted with water, filtered to remove solid impurities and the filter cake was washed with EtOAc. The filtrate was diluted with brine and EtOAc, phases were separated and the water phase was extracted with EtOAc (2×). The combined organic phases were dried using Na2SO4, filtered and evaporated. The crude product was purified by silica gel column chromatography eluting with a gradient of MeOH (containing 0.3% of aqueous NH3, 0-4%) in DCM, followed by another purification on silica gel eluting with a mixture of MeOH (containing 0.3% of aqueous NH3)/DCM (98/2). Fractions containing the product were combined, concentrated. The solid was suspended in EtOAc, sonicated, filtered and dried to yield the title compound as a white solid. (UPLC-MS 3) tR 0.86 min, ESI-MS 512.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 13.30 (s, 1H), 8.27 (s, 1H), 7.78 (s, 1H), 7.54 (s, 1H), 6.88 (t, 1H), 5.49 (s, 1H), 4.47 (t, 2H), 3.98-3.87 (m, 4H), 3.53 (t, 2H), 3.43-3.28 (m, 11H), 2.85 (t, 2H), 1.96-1.86 (m, 2H).

Provenance & Evidence