Sodium hydride → CS-526

HRID 1582323Notes

Reaction equation

HRID 1582323 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:13]1[N:14]=[N:15][CH:16]=[C:17]2[C:21]([CH3:22])=[C:20]([CH3:23])[N:19]([CH2:24][C@H:25]3[CH2:27][C@@H:26]3[CH3:28])[C:18]=12>O1CCCC1>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][O:7][C:13]2[N:14]=[N:15][CH:16]=[C:17]3[C:21]([CH3:22])=[C:20]([CH3:23])[N:19]([CH2:24][C@H:25]4[CH2:27][C@@H:26]4[CH3:28])[C:18]=23)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680224-Fluorobenzylic alcoholHCID 121104577-Chloro-2,3-dimethyl-1-[(1S,2S)-2-methylcyclopropylmethyl]pyrrolo[2,3-d]pyridazine

Product 1

HCID 9833312CS-526Yield 66.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of p-fluorobenzyl alcohol (1.45 g, 11.5 mmol) in tetrahydrofuran (2 ml) was added dropwise to a solution of sodium hydride (0.26 g, 10.8 mmol) in tetrahydrofuran (6 ml) and the mixture was stirred at room temperature for 30 minutes. A solution of 7-chloro-2,3-dimethyl-1-[(1S,2S)-2-methylcyclopropylmethyl]pyrrolo[2,3-d]pyridazine (2.50 g, 10.0 mmol) in tetrahydrofuran (13 ml) was added dropwise to the reaction mixture at room temperature and the mixture was heated under reflux for 3 hours. After the reaction was completed, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then concentrated in vacuo. Hexane was added to the concentrated solution, and the precipitate was collected by filtration and then recrystallized from a mixture of ethyl acetate and hexane to afford the title compound (2.25 g, 66.4%) as pale brown crystals.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3 hours
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. additionHexane was added to the concentrated solution
  8. filtrationthe precipitate was collected by filtration
  9. customrecrystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-d7b1e1e7be8448319a01f634bf00c369
Source dataset
uspto-grants-2004_05
Patent number
US06734181B2

Reaction notes

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