Cesium carbonate → 6-chloro-4-(5-(4-hydroxy-4-methylpiperidin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

Participants

Reaction Conditions

Reaction Steps

A solution of 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (902 mg, 4.04 mmol), 1-(6-aminopyridin-3-yl)-4-methylpiperidin-4-ol (761 mg, 3.67 mmol), Xantphos (159 mg, 275 μmol) and cesium carbonate (3.59 g, 11 mmol) in dry dioxane (10 ml) was vacuum de-gassed and placed under an argon atmosphere. To this mixture was added tris(dibenzylideneacetone)dipalladium (0) (38 mg, 36.7 μmol) and the vacuum de-gas cycle was repeated. The material was heated at 90° C. (oil bath) with vigorous stirring overnight. The flask was cooled to ambient and the contents were filtered through a plug of celite, rinsing well with dioxane, and concentrating. The product was purified by preparative HPLC on silica gel, using a gradient of 5% to 70% ethylacetate/hexane. This provided the desired product as a light yellow solid (807 mg 62.9%). (M+H)+=350, 352 m/e.

Provenance & Evidence