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

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Reaction Conditions

Reaction Steps

A solution of 5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine (342 mg, 2.25 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (527 mg, 2.36 mmol), cesium carbonate (2.2 g, 6.74 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethlxanthene (195 mg, 0.34 mmol) in dioxane (15 ml) was flushed with argon before tris(dibenzylideneacetone)dipalladium(0) (154 mg, 0.17 mmol) was added and the resulting solution was heated in a sealed tube at 110° C. for 18 h. The mixture was cooled to room temperature and filtered through celite. The cake was washed with dichloromethane. The combined filtrate and washes were diluted with 3M HCl and separated. The DCM layer was back extracted with aqueous HCl and discarded. The combined aqueous HCl extracts were made basic with 3M NaOH. The resulting aqueous phase was extracted 2 times with DCM. The combined DCM extracts were concentrated in vacuo and the resulting solid was triturated with ethyl ether, filtered, and dried to give 6-chloro-2-methyl-4-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridazin-3(2H)-one (455 mg, 69%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.35 (s, 3 H) 2.81 (t, J=5.48 Hz, 2 H) 3.51 (s, 2 H) 3.63 (s, 3 H) 4.03 (t, J=5.48 Hz, 2 H) 5.98 (s, 1 H) 7.71 (s, 1 H) 9.60 (s, 1 H).

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