3-Furanol, tetrahydro- → 3,6-Dimethyl-4-(tetrahydrofuran-3-yloxy)-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine

HRID 1067270Notes

Reaction equation

HRID 1067270 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:8][CH2:7][O:6][CH2:5]1.Cl[C:10]1[CH:15]=[C:14]([CH3:16])[N:13]=[C:12]2[N:17]([C:21]3[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][C:22]=3[CH3:29])[N:18]=[C:19]([CH3:20])[C:11]=12>CCCCCC.O1CCCC1>[CH3:20][C:19]1[C:11]2[C:12](=[N:13][C:14]([CH3:16])=[CH:15][C:10]=2[O:3][CH:4]2[CH2:8][CH2:7][O:6][CH2:5]2)[N:17]([C:21]2[C:26]([CH3:27])=[CH:25][C:24]([CH3:28])=[CH:23][C:22]=2[CH3:29])[N:18]=1

Participants

6

Reactant 3

HCID 99603-Furanol, tetrahydro-HCID 24758Sodium hydrideHCID 211929064-chloro-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 224526183,6-Dimethyl-4-(tetrahydrofuran-3-yloxy)-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

Sodium hydride (60% in oil, 176 mg, 4.4 mmol) was washed with hexane and suspended in 2 ml of tetrahydrofuran. 3-Hydroxytetrahydrofuran (1 ml) was added and stirred at room temperature for 5 minutes. A solution of 4-chloro-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine (200 mg, 0.665 mmol) in 1 ml of THF was added and the resulting mixture was heated at reflux for 8 hours. The mixture was quenched with water and extracted with EtOAc. The organic layer was dried and concentrated to give 334 mg of crude product. The crude material was purified through silica gel column chromatography using 1% methanol in chloroform as eluent to give 127 mg of a beige solid, mp 117-119° C.; IR(KBr) 2950, 1600, 1580 cm−1; high MS, calc. 351.1941, found, 351.19386; 1H NMR (CDCl3): 6.90 (s, 2H), 6.15 (s, 1H), 5.07 (m, 1H), 3.9-4.05 (m, 4H), 2.6 (s, 3H), 2.47 (s, 3H), 2.38 (s, 3H), 2.2-2.3 (m, 2H), 1.98 (s, 3H), 1.96 (s, 3H) ppm.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 8 hours
  3. customThe mixture was quenched with water
  4. extractionextracted with EtOAc
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customto give 334 mg of crude product
  8. customThe crude material was purified through silica gel column chromatography

Sources & evidence

ORD record
ord-36e248f9fdb044379fe9c98858efddc2
Source dataset
uspto-grants-2001_06
Patent number
US06248753B1

Reaction notes

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