Lawesson's reagent → (3R,4R)-tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of (3R,4R)-tert-butyl-4-methyl-3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl-carbamoyl)-piperidine-1-carboxylate (53 g, 100 mmol) and Lawesson's reagent (22.4 g, 55.2 mmol) in 1,4-dioxane (500 mL) was heated at about 80° C. for about 1 h. The reaction was allowed to cool to ambient temperature and then was partitioned between EtOAc (1000 mL) and saturated aqueous NaHCO3 (700 mL). The organic layer was washed with additional saturated aqueous NaHCO3 (700 mL), dried over anhydrous Na2SO4, filtered then concd in vacuo. The resulting residue was dissolved in 1,4-dioxane (500 mL) then mercury (II) trifluoroacetate (54.0 g, 127 mmol) was added. The reaction was stirred at about 25° C. for about 1 h. The reaction was partitioned with saturated aqueous Na2S2O3 (500 mL)/water (500 mL) with DCM (1000 mL). The layers were filtered through Celite® and the Celite® pad was washed with DCM (500 mL). The combined layers were separated then the organic layer was washed with saturated aqueous NaHCO3 (800 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered, and then coned in vacuo. The resulting residue was purified on silica gel (330 g) using 0-40% EtOAc in DCM to give (3R,4R)-tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate (40.5 g, 79%) as a yellow foam: LC/MS (Table 1, Method b) Rt=2.62 min; MS m/z: 510 (M+H)+.

Provenance & Evidence