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

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To a solution of 5-(4-tert-butylphenylsulfonyl)-2-hydrazinyl-5H-pyrrolo[2,3-b]pyrazine (0.40 g, 1.2 mmol, Preparation #3) and DIEA (0.20 mL, 1.2 mmol) in 1,4-dioxane (12 mL) at about 0° C. was added 2-methylcyclohexanecarbonyl chloride (0.19 g, 1.2 mmol, Preparation #4). After the complete addition, the ice bath was removed and the reaction was allowed to warm to ambient temperature. After about 1 h, SOCl2 (0.42 mL, 5.8 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 and then 2 M aqueous Na2CO3 (2N, 11.6 mL, 23.2 mmol) and MeOH (12 mL) were added. The reaction was heated at about 90° C. for about 3 days. The reaction was concentrated under reduced pressure and then partitioned between EtOAc (50 mL) and saturated aqueous NaHCO3 (40 mL). The organic layer was separated and dried over anhydrous Na2SO4, filtered and the solvent was concentrated under reduced pressure. The residue was purified over silica gel (12 g) using EtOAc as the eluent and then further purified by RP-HPLC (Table 2, Method b). The combined product-containing fractions were concentrated under reduced pressure to remove the MeCN and the resulting precipitate was collected by vacuum filtration to afford 1-(2-methylcyclohexyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine as a white solid (0.10 g, 35%): LC/MS (Table 2, Method a) Rt=1.84 min; MS m/z: 256 (M+H)+.

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