Sodium hydride → (2-Chloro-pyrimidin-4-yl)-(5-tert-butyl-isoxazol-3-yl)-amine
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]=1Participants
5
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.