Cesium carbonate → 6-chloro-4-(5-ethyl-4,5,6,7-tetrahydro-pyrazolo[1,5-a]pyrazin-2-ylamino)-2-methyl-2H-pyridazin-3-one

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Reaction Conditions

Reaction Steps

In a 250 mL round-bottomed flask, 5-ethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine (350 mg, 2.11 mmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (471 mg, 2.11 mmol, Eq: 1.00), cesium carbonate (2.4 g, 7.37 mmol, Eq: 3.50) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (183 mg, 316 μmol, Eq: 0.15) were combined with dioxane (40 ml) and the reaction mixture was flushed with argon. Then bis(dibenzylideneacetone)palladium (90.8 mg, 158 μmol, Eq: 0.075) was added and the reaction mixture was heated at 90° C. for 18 hr. After cooling to room temperature it was diluted with 50 mL dichloromethane and water. The aqueous layer was back-extracted with DCM (2×25 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 0% to 3% MeOH in DCM). The pure fractions were triturated with EtOAc. Mixed fractions and filtrate were purified by chromatography to afford pure product, which was combined with the triturated solid to afford the desired product (500 mg). (M+H)+=309 m/e.

Provenance & Evidence