Diisopropylethylamine → HCID 25230750, compound

Participants

Reaction Conditions

Reaction Steps

A solution of pyridin-3-yl-acetic acid hydrochloride salt (57.3 mg, 0.33 mmol) in methylene chloride (1.84 mL) was treated with N,N,N′,N′-tetramethyl-O—(N-succinimidyl)uronium tetrafluoroborate (119 mg, 0.39 mmol) and N,N-diisopropylethylamine (0.17 mL, 0.99 mmol). The resulting solution was stirred at 25° C. for 2.5 h. At this time, 2-[3,5-dichloro-4-(1-hydroxymethyl-5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carbonitrile (200 mg, 0.42 mmol) was added to the reaction. The reaction mixture was stirred at 25° C. for 18 h. At this time, the reaction mixture was diluted with methylene chloride (50 mL) and washed with water (3×150 mL). The organics were dried over sodium sulfate, filtered, rinsing with methylene chloride and concentrated in vacuo. Biotage flash chromatography (40S, 1-4% methanol/methylene chloride) followed by supercritical fluid chromatography (Daicel OD column, 60% methanol) afforded pyridin-3-yl-acetic acid 3-[2,6-dichloro-4-(6-cyano-3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-phenoxy]-5-isopropyl-6-oxo-6H-pyridazin-1-ylmethyl ester (43.2 mg, 22%) as a yellow solid. ES+-HRMS m/e calcd for C25H19N7O6Cl2 (M+H+) 584.0847, found 584.0848.

Provenance & Evidence