Water → 1-(4-Methoxy-phenyl)-7a-morpholin-4-yl-7-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-c]pyridin-3-carboxylic acid ethyl ester

HRID 860828

Reaktionsgleichung

Reaktionsgleichung von HRID 860828
[CH2:1]([O:3][C:4](=[O:17])[C:5](Cl)=[N:6][NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1)[CH3:2].[N:18]1([C:24]2[C:25](=[O:30])[NH:26][CH2:27][CH2:28][CH:29]=2)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(N(CC)CC)C.O>C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:5]1[CH:29]2[C:24]([N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)([C:25](=[O:30])[NH:26][CH2:27][CH2:28]2)[N:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[N:6]=1)=[O:17])[CH3:2]

Komponenten

6

Edukt 4

HCID 962WaterHCID 8471TriethylamineHCID 21829645Ethyl 2-chloro-2-[2-(4-methoxyphenyl)hydrazono]acetateHCID 218914603-(Morpholin-4-yl)-1,2,5,6-tetrahydropyridin-2-one

Produkt 1

HCID 208161461-(4-Methoxy-phenyl)-7a-morpholin-4-yl-7-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-c]pyridin-3-carboxylic acid ethyl esterAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

A solution of chloro[(4-methoxyphenyl)hydrazono]acetic acid ethyl ester (34, 582 mg, 2.0 mmol) in ethyl acetate (EtOAc, 10 mL) was treated with 3-morpholin-4-yl-5,6-dihydro-1H-pyridin-2-one (45, 364 mg, 2.0 mmol, 1.0 equiv) at 0–5° C. under N2, and the resulting reaction mixture was treated with triethylamine (TEA, 505 mg, 0.70 mL, 5.0 mmol, 2.5 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 treated with water (10 mL) and EtOAc (10 mL). The two layers were separated, and the aqueous layer was extracted with EtOAc (3×10 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)-7a-morpholin-4-yl-7-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-c]pyridin-3-carboxylic acid ethyl ester (51, 523 mg, 805 mg theoretical, 65%) as pale-yellow oil, which solidified upon standing at room temperature in vacuo. For 51, CIMS m/z 401 (M+−H, C20H26N4O5).

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-db60ead5131740a4b9c6d5f514252e28
Quelldatensatz
uspto-grants-2006_12
Patentnummer
US07153960B2

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