Water → 6-(4-Hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid methyl ester

HRID 2279107Notes

Reaction equation

HRID 2279107 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]2[C:20]([CH3:21])=[N:19][NH:18][C:7]=2[N:8]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH:10]=1)=[O:4].[O:22]1[CH:27]=[CH:26][CH2:25][CH2:24][CH2:23]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[C:6]2[C:20]([CH3:21])=[N:19][N:18]([CH:23]3[CH2:24][CH2:25][CH2:26][CH2:27][O:22]3)[C:7]=2[N:8]=[C:9]([C:11]2[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=2)[CH:10]=1)=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178497272HCID 178497272, compound

Product 1

HCID 1363597696-(4-Hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid methyl esterYield 57%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6-(4-hydroxy-phenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid methyl ester (15.0 g), 3,4-dihydro-2H-pyran (24 mL) and p-toluenesulfonic acid monohydrate (3.0 g) in THF (400 mL) was stirred at r.t. until the reaction was complete. Water was added and the mixture was extracted with ethyl acetate, the combined organic phases were washed with water and brine, dried over magnesium sulfate and concentrated. The residue was chromatographed over a short path column (silica, heptane/ethyl acetate gradient). The product containing fractions were combined, concentrated, and the residue was triturated with ether to give 6-(4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid methyl ester (11 g, 57% yield).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washthe combined organic phases were washed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue was chromatographed over a short path column (silica, heptane/ethyl acetate gradient)
  6. additionThe product containing fractions
  7. concentrationconcentrated
  8. customthe residue was triturated with ether

Sources & evidence

ORD record
ord-f6ecadad42e2491c9b9a641d9de6bcd5
Source dataset
uspto-grants-2015_09
Patent number
US09133181B2

Reaction notes

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