1,1'-Carbonyl-di-(1,2,4-triazole) → HCID 118037015, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 683 mg, 3.56 mmol) in anhydrous DMF (6 ml) was added drop wise to a mixture of di(1H-1,2,4-triazol-1-yl)methanone (648 mg, 3.56 mmol) and DMF (6 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 4-(2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)morpholin-3-one (intermediate 333, 683 mg, 1.78 mmol) in DMF (6 ml) was added. The suspension was allowed to warm to room temperature, was continued to stir for 17 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 washed with brine, 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, 1-6%) in DCM. Fractions containing the product were combined, concentrated. The solid was precipitated from DCM and n-hexane, sonicated, filtered and dried to yield the title compound as a white solid. (UPLC-MS 3) tR 0.83 min, ESI-MS 526.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 8.27 (s, 1H), 7.72 (s, 1H), 7.55 (s, 1H), 6.88 (t, 1H), 5.34 (s, 1H), 4.23 (d, 2H), 4.10-3.84 (m, 4H), 3.71-3.24 (m, 15H), 2.92-2.82 (m, 2H), 1.98-1.87 (m, 2H).

Provenance & Evidence