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 896807Notes

Reaction equation

HRID 896807 reaction equation
[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]

Participants

6

Reactant 4

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

Product 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 esterYield 65%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-db24c6023a58491595be1d83142813b6
Source dataset
uspto-grants-2005_07
Patent number
US06919451B2

Reaction notes

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