Sodium hydride → HCID 18445309, compound

HRID 459918Notes

Reaction equation

HRID 459918 reaction equation
[CH2:1]([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][N:20]=1>CN(C=O)C>[CH2:1]([NH:8][CH:9]1[CH2:14][CH2:13][CH:12]([O:15][C:19]2[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][N:20]=2)[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 11117199HCID 11117199, compound

Product 1

HCID 18445309HCID 18445309, compoundYield 88.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Add dropwise a solution of 4-benzylamino-cyclohexanol (675 mg, 3.28 mmol) in DMF (2 mL) to a suspension of NaH (196 mg, 4.92 mmol) in DMF (3 mL). Stir at room temperature for 45 min then at 50° C. for additional 40 min. Add a solution of 6-chloro-nicotinonitrile (500 mg, 3.61 mmol) in DMF (1.8 mL) dropwise and stir overnight at 60° C. Cool down the reaction mixture and evaporate the solvent. Wash the residue with water (10) and extract with EtOAc/hex (2/1, 15 mL). Combine the organic layers and dry over sodium sulfate. Filter and concentrate. Purify the resulting residue through an SCX column. Further purified by chromatography [CH2Cl2/NH3 (2.0M in methanol) 20/1] to provide the title compound (890 mg, 88%).

Workup

  1. waitat 50° C. for additional 40 min
  2. stirringstir overnight at 60° C
  3. temperatureCool down the reaction mixture
  4. customevaporate the solvent
  5. washWash the residue with water (10)
  6. extractionextract with EtOAc/hex (2/1, 15 mL)
  7. dry with materialCombine the organic layers and dry over sodium sulfate
  8. filtrationFilter
  9. concentrationconcentrate
  10. customPurify the resulting residue through an SCX column
  11. customFurther purified by chromatography [CH2Cl2/NH3 (2.0M in methanol) 20/1]

Sources & evidence

ORD record
ord-291b49277f8743c3a9feecd7a71a60d1
Source dataset
uspto-grants-2007_03
Patent number
US07196100B2

Reaction notes

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