Citric Acid → ethyl 2-(4-iodo-1H-pyrazolo[3,4-b]pyridin-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanoate

HRID 1802890Notes

Reaction equation

HRID 1802890 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12.Br[CH:12]([CH2:18][CH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[C:13]([O:15][CH2:16][CH3:17])=[O:14].O1CCC(C=CC(OCC)=O)CC1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([CH2:18][CH:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:9]=[CH:10][C:3]=12

Participants

7

Reactant 5

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 54040092ethyl 3-(tetrahydro-2H-pyran-4-yl)-2-propenoateHCID 576428014-Iodo-1H-pyrazolo[3,4-b]pyridineHCID 58380608ethyl 2-bromo-3-(tetrahydro-2H-pyran-4-yl)propanoate

Product 1

HCID 58380598ethyl 2-(4-iodo-1H-pyrazolo[3,4-b]pyridin-1-yl)-3-(tetrahydro-2H-pyran-4-yl)propanoateYield 53.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-iodo-1H-pyrazolo[3,4-b]pyridine (1.72 g), a 1:1 mixture (3.1 g) of ethyl 2-bromo-3-(tetrahydro-2H-pyran-4-yl)propanoate and ethyl 3-(tetrahydro-2H-pyran-4-yl)-2-propenoate, potassium carbonate (1.0 g) and N,N-dimethylformamide (15 mL) was stirred overnight at room temperature. To the reaction mixture was added aqueous citric acid solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to give the title compound (1.6 g, yield 53%) as a colorless oil from the fraction eluted with ethyl acetate-hexane (35:75, volume ratio). MS: 430 (MH+).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with water and saturated brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-bd26cdef16bb4e299bf9e1c906bec775
Source dataset
uspto-grants-2013_01
Patent number
US08349886B2

Reaction notes

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