Hydrochloric Acid → 4-(6-acetyl-7-amino-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylic acid

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Reaction Steps

To a solution of ethyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-(1-ethoxyvinyl)-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylate (167 mg, 0.211 mmol) in dioxane (2 mL) was added 2 mL of HCl (4 N, aq) at 0° C. The reaction mixture was stirred at rt for 1 h, then 60° C. for 1 h. The reaction mixture was evaporated to dryness. The residue was treated with LiOH (10 eq) in THF/MeOH/H2O (2/1/1 mL) at 80° C. overnight. The reaction mixture was carefully acidified with HCl (aq) to pH=6-7, and evaporated to dryness. The crude product was purified by a reverse phase HPLC to afford 4-(6-acetyl-7-amino-3-(1-phenyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-1-(hydroxymethyl)cyclohexanecarboxylic acid as a pale yellow solid (27.7 mg). HPLC-MS TR=4.39 min (UV 254 nm, 10 min method); mass calculated for formula C25H26N6O4 474.2, observed LCMS m/z 475 (M+H).

Provenance & Evidence