Water → 1-(4-Chloro-phenyl)-6-(4-iodo-phenyl)-7a-morpholin-4-yl-7-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid methyl ester

Participants

Reaction Steps

A solution of bromo[(4-chlorophenyl)hydrazono]acetic acid methyl ester (31, 582 mg, 2.0 mmol) in toluene (6 mL) was treated with 1-(4-iodo-phenyl)-3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (10, 768 mg, 2.0 mmol, 1.0 equiv) at 0–5° C. under N2, and the resulting reaction mixture was treated with triethylamine (TEA, 404 mg, 0.56 mL, 4.0 mmol, 2.0 equiv) at 0–5° C. under N2. The reaction mixture was then warmed up to room temperature for 30 min before being warmed up to 70° C. for an additional 3 h. When HPLC and TLC showed that the reaction was complete, the reaction mixture was treated with water (10 mL) and EtOAc (10 mL). The two layers were separated, and the aqueous layer was extracted with EtOAc (2×10 mL). The combined organic extracts were washed with saturated NaCl aqueous solution (5 mL), dried over MgSO4, and concentrated in vacuo. The residue was directly purified by flash column chromatography (SiO2, 15–30% EtOAc/hexane gradient elution) to afford the desired 1-(4-chloro-phenyl)-6-(4-iodo-phenyl)-7a-morpholin-4-yl-7-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid methyl ester (52, 1.13 g, 1.19 g theoretical, 95%) as pale-yellow oil, which solidified upon standing at room temperature in vacuo. For 52, CIMS m/z 595/597 (M++H, C24H24ClIN4O4).

Provenance & Evidence