Methanol → Methyl 8-(4-(tert-butoxycarbonyl)piperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A 300 mL pressure vessel was charged with tert-butyl 4-(5-bromo-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate (prepared as described in Example 1 steps 1-4, 10.0 g, 26 mmol), CuI (1.5 g, 7.8 mmol), Pd(dppf)Cl2 (6.4 g, 7.8 mmol), N,N-diisopropylethylamine (10 mL) and MeOH (100 mL). The vessel was charged with carbon monoxide (3.5 bar) and the reaction mixture was magnetically stirred at 100° C. for 12 h. Work-up: after the reaction mixture was cooled to room temperature, the vessel was opened. The reaction solution was diluted with saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (200 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with 2% MeOH in CH2Cl2, to afford 7.0 g (73%) of the product as a white solid. MS m/z: 363 (M+H+).

Provenance & Evidence