Sodium hydride → (2-Chloro-pyrimidin-4-yl)-(5-tert-butyl-isoxazol-3-yl)-amine

HRID 1241588Notes

Reaction equation

HRID 1241588 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[O:4][N:3]=1.[H-].[Na+].[Cl:13][CH:14]1[N:19](Cl)[CH:18]=[CH:17][CH:16]=[N:15]1>CN(C=O)C>[Cl:13][C:14]1[N:19]=[C:18]([NH:1][C:2]2[CH:6]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[O:4][N:3]=2)[CH:17]=[CH:16][N:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-HCID 219364672,3-Dichloropyrimidine

Product 1

HCID 21936452(2-Chloro-pyrimidin-4-yl)-(5-tert-butyl-isoxazol-3-yl)-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-amino-5-t-butylisoxazole (922 mg 6.58 mmol) in 15 mL of DMF at 0° C. was added 268 mg (6.71 mmol) of NaH (60% dispersion in mineral oil) in 4 portions over 1 min. The resulting mixture was stirred at 0° C. for 30 min when 1.0 g (6.71 mmol) of 2,3-dichloropyrimidine was added in 1 portion. The resulting mixture was warmed to RT (ice melt in dewar) and was stirred at RT for 22 h. The reaction mixture was quenched with saturated aqueous NH4Cl and diluted with H2O and EtOAc. The organic layer was washed 1× with brine. The combined aqueous layer and brine wash were extracted 1× with EtOAc. The combined organics were dried over Na2SO4, concentrated and purified by flash chromatography (elution with 2/1 hexanes/EtOAc) to give (2-chloro-pyrimidin-4-yl)-(5-tert-butyl-isoxazol-3-yl)-amine as a yellowish white solid.

Workup

  1. additionwas added in 1 portion
  2. customThe reaction mixture was quenched with saturated aqueous NH4Cl
  3. additiondiluted with H2O and EtOAc
  4. washThe organic layer was washed 1× with brine
  5. washThe combined aqueous layer and brine wash
  6. extractionwere extracted 1× with EtOAc
  7. dry with materialThe combined organics were dried over Na2SO4
  8. concentrationconcentrated
  9. custompurified by flash chromatography (elution with 2/1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-c406ae233e1340b5963529f42838c920
Source dataset
uspto-grants-2006_10
Patent number
US07115617B2

Reaction notes

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