1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 46178510, compound

Participants

Reaction Conditions

Reaction Steps

Under an argon atmosphere, 225 mg (0.24 mmol) of 6-bromo-1-{3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]benzyl}-1H-1,2,3-triazolo[4,5-b]pyrazine are dissolved in 5 ml of ethylene glycol dimethyl ether, and 102 mg (0.48 mmol) of tripotassium phosphate trihydrate and 55 mg (0.26 mmol) of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole are added. The reaction mixture is evacuated and flushed with argon twice. 14 mg (0.02 mmol) of bis(triphenylphosphine)palladium(II) chloride are added, the mixture is again evacuated and flushed argon. The reaction mixture is stirred at 80° C. for 16 hours. 10 ml of water are added to the reaction mixture, during which an oil precipitates out. This is extracted with dichloromethane and with dichloromethane comprising about 10% of MeOH, the aqueous phase is adjusted to pH 14 using 32% NaOH and again extracted with dichloromethane. The combined organic phases are dried over sodium sulfate and purified by means of preparative HPLC, giving 42 mg of 6-(1-methyl-1H-pyrazol-4-yl)-1-{3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]benzyl}-1H-1,2,3-triazolo[4,5-b]-pyrazine (“A2”); the product is in the form of the TFA salt; Rt.=2.26 (method A), LCMS: 499 (M+H);

Provenance & Evidence