Sodium Carbonate → Benzyl 4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)piperidine-1-carboxylate

Participants

Reaction Steps

Benzyl 4-(chlorocarbonyl)piperidine-1-carboxylate (0.41 g, 1.4 mmol, Preparation #5) was added to a solution of 5-(4-tert-butylphenylsulfonyl)-2-hydrazinyl-5H-pyrrolo[2,3-b]pyrazine (0.50 g, 1.4 mmol, Preparation #3) and DIEA (0.25 mL, 1.4 mmol) in 1,4-dioxane (15 mL) at about 0° C. After the complete addition, the ice bath was removed and the reaction was allowed to warm to ambient temperature. After about 1 h, SOCl2 (0.53 mL, 7.2 mmol) was added and the reaction was heated at about 90° C. for about 1 h. The reaction was allowed to cool to ambient temperature then aqueous Na2CO3 (2 M, 14.5 mL, 29.0 mmol) was added and the reaction was heated at about 90° C. for about 3 days. The reaction was partitioned with EtOAc (50 mL) and saturated aqueous NaHCO3 (40 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified over silica gel (12 g) eluting with 50-100% EtOAc in heptane to afford benzyl 4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)piperidine-1-carboxylate as a yellow solid (0.34 g, 61%): LC/MS (Table 2, Method a) Rt=1.89 min; MS m/z: 377 (M+H)+.

Provenance & Evidence