Hydrochloric Acid → 6-(4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl-methanone

HRID 2279109Notes

Reaction equation

HRID 2279109 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([C:24](O)=[O:25])[C:11]3[C:16]([CH3:17])=[N:15][N:14]([CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][O:19]4)[C:12]=3[N:13]=2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.C[O-].[Na+].Cl>C(Cl)Cl.CCOC(C)=O>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]([CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][O:19]4)[N:15]=[C:16]([CH3:17])[C:11]3=[C:10]([CH:24]=[O:25])[CH:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 10942334Sodium MethoxideHCID 1363597706-(4-Hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid

Product 1

HCID 1372400556-(4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl-methanoneYield 57.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 3.80 g of 6-(4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid in 100 ml of DCM were added 5.5 ml of Hünig's base, 6.48 g of BEP and 2.41 g of (2R,5S)-dimethyl-1-benzylpiperazine. The reaction was stirred overnight at r.t. Then 3 ml of sodium methanolate (30% in methanol) were added, and the reation was stirred for 30 min. The pH was then brought to 5 by the addition of 2 M aqueous hydrochloric acid. The mixture was then diluted with EtOAc and the layers were separated. The organic layer was washed with saturated aqueous sodium bicarbonate solution, saturated aqueous ammonium chloride solution and water, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica, heptane/EtOAc gradient) to obtain 2.10 g (36%) of the title compound.

Workup

  1. stirringthe reation was stirred for 30 min
  2. customthe layers were separated
  3. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution, saturated aqueous ammonium chloride solution and water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (silica, heptane/EtOAc gradient)

Sources & evidence

ORD record
ord-100ac977ed48485c8c36df0802fa0fb6
Source dataset
uspto-grants-2015_09
Patent number
US09133181B2

Reaction notes

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