Hydrochloric Acid → ethyl 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxo-1-piperidinyl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate

A solution of chloro[(4-methoxyphenyl)hydrazono]acetic acid ethyl ester (34, 470 mg, 1.3 mmol) in EtOAc (4 mL) was treated with 3-morpholin-4-yl-1-[4-(2-oxo-piperidin-1-yl)-phenyl]-5,6-dihydro-1H-pyridin-2-one (63, 334 mg, 1.3 mmol, 1.0 equiv) at 0–5° C. under N2, and the resulting reaction mixture was treated with triethylamine (TEA, 263 mg, 0.33 mL, 2.6 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 reflux for an additional 6 h. When HPLC and TLC showed that the reaction was complete, the reaction mixture was cooled down to 5–10° C. before being treated dropwise with a 4.0 N aqueous HCl solution (1.7 mL, 6.5 mmol, 5.0 equiv) at 0–5° C. The resulting mixture was stirred at 5–20° C. for 4 h. The resulting slurry was then treated with water (10 mL) and EtOAc (10 mL) before the two layers were separated. 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, 15–40% EtOAc/hexane gradient elution) to afford the desired 1-(4-methoxy-phenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)-phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylic acid ethyl ester (65, 423 mg, 635 mg theoretical, 67% for two steps) as pale-yellow solids, which solidified upon standing in vacuo at room temperature. For 65, CIMS m/z 489 (M++H, C27H28N4O5).

1. customthe resulting reaction mixture
2. temperaturebefore being warmed up
3. temperatureto reflux for an additional 6 h
4. temperaturethe reaction mixture was cooled down to 5–10° C.
5. customwere separated
6. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
7. washThe combined organic extracts were washed with saturated NaCl aqueous solution (5 mL)
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customThe residue was directly purified by flash column chromatography (SiO2, 15–40% EtOAc/hexane gradient elution)

ORDレコード

ord-2eb0c067e33844558c67a51e3b502ff0

出典データセット

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07153960B2