Tetrahydrofuran → 1-[3-Ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-yl]ethanone

HRID 2240176Notes

Reaction equation

HRID 2240176 reaction equation
[I-].[Li+].[CH2:3]([Li])CCC.[CH2:8]([C:10]1[C:18]2[C:13](=[N:14]C(C#N)=CC=2)[N:12]([CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:11]=1)[CH3:9].[O:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Al]>[CH2:8]([C:10]1[C:18]2[C:13](=[N:14][C:30]([C:31](=[O:27])[CH3:3])=[CH:29][CH:28]=2)[N:12]([CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:11]=1)[CH3:9]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 66321Lithium iodideHCID 687090213-ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-carbonitrileHCID 178418339Butyllithium

Product 1

HCID 598108381-[3-Ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-yl]ethanoneYield 70.4%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 5359268AluminumSolvent

Procedure

Methyltriphenylphosphonium bromide (4.64 g, 0.0130 mol) and lithium iodide (0.48 g, 0.0036 mot) were mixed in tetrahydrofuran (70 mL) in a 3-necked flask under an atmosphere of nitrogen. The flask was wrapped in aluminum foil to exclude light, and chilled to 0° C. n-Butyllithium (5.8 mL, 2.5 M in hexanes, 0.014 mol) was then added and the resulting mixture stirred for 30 minutes. A solution of 3-ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-carbonitrile (1.85 g, 7.22 mmol) in tetrahydrofuran (19.8 mL) was then added and the reaction stirred at 50° C. for 90 minutes. After cooling to room temperature, the product was extracted using dichloromethane (250 mL). The extract was washed brine and concentrated to afford the crude product as a semi-solid, which was purified by flash chromatography on silica gel using a 10-50% hexane:ethyl acetate gradient over 10 minutes (flow rate 20 mL/min). Concentration of the organics afforded 1.39 g (70.4%) of 1-[3-Ethyl-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-6-yl]ethanone as a colorless oil. LC/MS (EI) tR 3.72 (Method E), m/z 274.1 (M++1). All reagents were stored in a desiccator prior to use.

Workup

  1. additionwas then added
  2. stirringthe reaction stirred at 50° C. for 90 minutes
  3. extractionthe product was extracted
  4. washThe extract was washed brine
  5. concentrationconcentrated
  6. customto afford the crude product as a semi-solid, which
  7. customwas purified by flash chromatography on silica gel using a 10-50% hexane
  8. waitethyl acetate gradient over 10 minutes (flow rate 20 mL/min)

Sources & evidence

ORD record
ord-467ea73595e743d49bc478276e5c4029
Source dataset
uspto-grants-2010_05
Patent number
US07723348B2

Reaction notes

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