Water → HCID 178451737, compound

Participants

Reaction Steps

A flask charged with 7-chloroimidazo[1,2-c]pyrimidin-5(6H)-one (Preparation H, 1.75 g, 10.3 mmol), tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine-1-carboxylate (4.00 g, 10.3 mmol), potassium phosphate (4.38 g, 20.6 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.738 g, 1.55 mmol), and tris(dibenzylideneacetone)dipalladium (0.473 g, 0.516 mmol) was evacuated and backfilled with argon. Isopropanol (50 mL) and water (0.744 mL, 41.3 mmol) were added. The reaction was fitted with a septum and argon was bubbled through the reaction for 20 minutes before it was sealed and allowed to proceed at 90° C. for 6 hours. The reaction was recharged with catalyst, argon was bubbled through for 10 minutes, and the reaction was sealed and allowed to react at 90° C. for two days. The solvent was concentrated under reduced pressure, 200 mL of 2:1 2.5M potassium hydroxide/methanol was added and the reaction was stirred for 1 hour. A large amount of solids were observed so another 200 mL of the above mentioned mixture was added and much of the solid was dissolved. The solid was collected by means of vacuum filtration through a pad of celite and was then washed with 200 mL of the above mentioned mixture. The rinse was isolated and the pH was adjusted with 1 M hydrochloric until pH=9. The resulting solids were collected by means of vacuum filtration. This solid was taken up in 300 mL of water and allowed to stir for 30 minutes before the solid was collected by means of vacuum filtration and washed with water. The solid was dried on high vacuum and triturated with methanol. The mixture was filtered and the solid was dried under high vacuum to afford tert-butyl 4-(4-(5-hydroxyimidazo[1,2-c]pyrimidin-7-yl)phenyl)piperidine-1-carboxylate (1.75 g, 4.44 mmol, 43.0% yield). MS (apci) m/z=395.2 (M+H).

Provenance & Evidence