2,5-Dimethoxytetrahydrofuran → 1-((1R,35)-3-(1H-pyrrol-1-yl)cyclopentyl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine

Participants

Reaction Steps

A solution of 2,5-dimethoxytetrahydrofuran (0.14 g, 1.1 mmol) in water (3 mL) was heated at about 100° C. for about 1.5 h. The solution was cooled to ambient temperature. A suspension of (1S,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclo-pentanamine hydro-chloride (0.10 g, 0.21 mmol, prepared using E from Preparation #B.1 and HCl) and NaOAc (0.05 g, 0.61 mmol) in DCM (5 mL) was added to the aqueous solution. The reaction mixture was stirred at ambient temperature for about 1 h followed by addition of additional 2,5-dimethoxytetrahydrofuran (0.14 g, 1.1 mmol). The reaction mixture was heated to about 40° C. for about 15 h. Additional 2,5-dimethoxytetrahydrofuran (0.14 g, 1.1 mmol) was added and the reaction mixture was stirred at about 40° C. for about 8 h then at about 35° C. for about 48 h. The reaction was diluted with DCM (10 mL) and water (10 mL). The layers were separated and the organic layer was washed with water (2×10 mL) and brine (10 mL), dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure to give 1-((1R,3S)-3-(1H-pyrrol-1-yl)cyclopentyl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.095 g, 99%) as a yellow residue: LC/MS (Table 1, Method a) Rt=2.42 min; MS m/z: 447 (M+H)+.

Provenance & Evidence