Hydrochloric Acid → 1-[2-(4-Chloro-3-methoxy-phenyl)-2,8-diaza-spiro[4.5]dec-8-yl]-2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone

Participants

Reaction Conditions

Reaction Steps

2-(4-Chloro-3-methoxy-phenyl)-1-oxo-2,8-diaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (90 mg, 1 equiv) was treated with 4 mL of 4N HCl in dioxane at rt for 1 h. The volatile was removed and to the residue were added 3 mL of THF and 3 mL of dichloromethane. After cooling to 0° C., the solution was treated with 2 mL of 1M LiAlH4 in THF over night (allowed to warm to room temperature). 10 drops of water, 10 drops of 1N NaOH, and then 10 drops of water were added. The organic layer was collected and dried under vacuum. The residue was taken up in 1 mL of DMF, and to the solution were added (4-Chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetic acid (55 mg, 1 equiv), HATU (95 mg, 1.1 equiv), TEA (150 μL, 3 equiv). After stirring at rt over night, the mixture was taken up in EtOAc, washed with saturated sodium NaHCO3. Purification by reverse phase HPLC (acetonitrile-H2O with 0.1% TFA as eluent) gave 1-[2-(4-Chloro-3-methoxy-phenyl)-2,8-diaza-spiro[4.5]dec-8-yl]-2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone. LCMS observed for (M+H)+: 505. Retention time: 5.28 minutes (Agilent Zorbax SB-C18, 2.1×50 mm, 5μ, 35° C.) using a 4.5 minutes gradient of 20% to 95% B with a 1.1 minutes wash at 95% B (A=0.1% formic acid/5% acetonitrile/94.9% water, B=0.1% formic acid/99.9% acetonitrile).

Provenance & Evidence