Hydrochloric Acid → 2-ethyl-4-hydroxy-N'-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbohydrazide

Participants

Reaction Conditions

Reaction Steps

To a scalemic mixture enriched in (1S,4S,5R)-5-ethyl-2-oxabicyclo[2.2.1]heptan-3-one (0.835 g, 5.96 mmol) in 1,4-dioxane (12 mL) was added 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (step D, 1.810 g, 5.96 mmol). The reaction mixture was heated at about 80° C. for about 16 h then cooled to ambient temperature. 1,4-Dioxane (25 mL) and trimethylaluminum (2 N in toluene, 9 mL, 18 mmol) were added sequentially. The reaction mixture was stirred at ambient temperature for about 30 min then aqueous HCl (1 N, 50 mL) was added dropwise and the reaction mixture was stirred for about 30 min. The layers were separated and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water (10 mL), saturated aqueous NaHCO3 (15 mL), brine (15 mL) and dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The residue was purified using silica gel chromatography eluting with 100% EtOAc to give a scalemic mixture enriched in (1S,2R,4S)-2-ethyl-4-hydroxy-N′-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)cyclopentanecarbo-hydrazide (1.887 g, 71%): LC/MS (Table 1, Method b) Rt=2.05 min; MS m/z: 444 (M+H)+.

Provenance & Evidence