Thioglycolic Acid → 2-[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]-2H-[1,2,4]triazine-3,5-dione

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]-3,5-dioxo-2,3,4,5-tetrahydro-[1,2,4]triazine-6-carboxylic acid (89) (1.0 g, 2.13 mmol) and thioglycolic acid (21.3 mL, 2.13 mmol) were heated at 170° C. for 3.5 h. At this time, the reaction was cooled to 25° C. and diluted with water (500 mL). The aqueous layer was brought to pH=4 by the addition of a saturated aqueous sodium bicarbonate solution. The solids that precipitated were collected by filtration, washed consecutively with water, petroleum ether, a pH=5 buffer and water. The solids were air-dried under house vacuum for 15 min and then dried under vacuum to give a light brown solid. This solid was dissolved in a 1N aqueous sodium hydroxide solution (100 mL) and extracted with ethyl acetate (1×120 mL). The aqueous layer was neutralized by the addition of a 1N aqueous hydrochloric acid solution (15 mL). The resulting solids were collected by filtration, washed with water (200 mL) and petroleum ether (100 mL), air-dried under house vacuum and then dried under vacuum to afford 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]-2H-[1,2,4]triazine-3,5-dione (90) (338 mg, 37%) as tan solid; ES(+)-HRMS m/e calcd for C16H13Cl2N5O3S (M+H)+ 426.0189, found 426.0189. Exact Mass=425.0116; Molecular weight=426.28

Provenance & Evidence