Sodium Carbonate → HCID 178453592, compound

Participants

Reaction Conditions

Reaction Steps

Thionyl chloride (0.030 mL, 0.41 mmol) was added dropwise to a solution of tert-butyl(trans-4-(2-oxo-2-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinyl)ethyl)cyclohexyl)methyl-carbamate (0.127 g, 0.228 mmol, prepared using M from trans-(4-aminomethylcyclohexyl)acetic acid hydrochloride [AstaTech], H from Example #1, Step D, HATU, TEA), TEA (0.160 mL, 1.15 mmol), and 1,4-dioxane (2.3 mL) under nitrogen. A reflux condenser was attached and the reaction mixture was warmed to about 80° C. After about 2 h, the solution was cooled to ambient temperature and aqueous Na2CO3 (2 M, 3.4 mL, 6.8 mmol) was added and the biphasic mixture was warmed to about 80° C. After about 2 h, aqueous NaOH (2 M, 0.570 mL, 1.14 mmol) was added due to slow rate of deprotection. After about 17 h, the mixture was allowed to cool to ambient temperature. The reaction solution was diluted with water (5 mL) and then extracted with EtOAc (2×10 mL). The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 2-8% MeOH in DCM to give tert-butyl(trans-4-((6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)methyl)cyclohexyl)methylcarbamate (0.0565 g, 63%): LC/MS (Table 1, Method a) Rt=1.85 min; MS m/z: 385 (M+H)+.

Provenance & Evidence