Sodium Carbonate → 1-cyclohexyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine

Participants

Reaction Steps

To a solution of 5-(4-tert-butylphenylsulfonyl)-2-hydrazinyl-5H-pyrrolo[2,3-b]pyrazine (0.39 g, 1.1 mmol; Preparation #3) and DIEA (0.20 mL, 1.1 mmol) in 1,4-dioxane (12 mL) at about 0° C. was added cyclohexanecarbonyl chloride (0.17 g, 1.1 mmol). The reaction was then warmed to ambient temperature for about 1 h. SOCl2 (0.41 mL, 5.6 mmol) was added and the reaction was heated to about 90° C. for about 1 h. The reaction was cooled to ambient temperature and aqueous Na2CO3 (2 M, 12 mL, 24 mmol) was added slowly followed by 1,4-dioxane (5 mL). The reaction was heated at about 60° C. for about 72 h. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The crude product was diluted with EtOAc (40 mL) and washed with saturated aqueous NaHCO3 (40 mL) and brine (40 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography eluting with a gradient of 0-100% heptane/EtOAc (12 g column) and dried in a vacuum oven at about 55° C. for about 18 h to give 1-cyclohexyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.109 g, 40%): LC/MS (Table 2, Method a) Rt=1.66 min; MS m/z: 242 (M+H)+.

Provenance & Evidence