تفاعل #171022

معادلة التفاعل

2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole

N,N-dimethylprop-2-yn-1-amine

pyrrolidine

→

3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)-N,N-dimethylprop-2-yn-1-amine

المردود 95.0%

ظروف التفاعل

المعالجة

1. 1
   أخرىdegassed DMF (2 mL)
2. 2
   أخرىconsumption of starting material
3. 3
   workup.ADDITIONThe mixture was diluted with EtOAc
4. 4
   غسيلwashed with brine
5. 5
   أخرىdried
6. 6
   تركيزconcentrated
7. 7
   أخرىPurification by column chromatography (0 to 15% MeOH/DCM)

الإجراء التجريبي

To a solution of 2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (250 mg, 0.43 mmol, 1.0 eq), N,N-dimethylprop-2-yn-1-amine (0.07 mL, 0.64 mmol, 1.5 eq) and pyrrolidine (0.05 mL, 0.64 mmol, 1.5 eq) in dry, degassed DMF (2 mL) were added PdCl2(dppf)2 (16 mg, 0.022 mmol, 5 mol %) and CuI (8 mg, 0.043 mmol, 10 mol %). The reaction mixture was heated at 80° C. for 16 h, at which time LCMS showed complete consumption of starting material. The mixture was diluted with EtOAc, washed with brine, dried and concentrated. Purification by column chromatography (0 to 15% MeOH/DCM) furnished 238 mg (95% yield) of 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)-N,N-dimethylprop-2-yn-1-amine as a brown oil: MS (EI): 584 (MH+).

المصدر