تفاعل #171098

معادلة التفاعل

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

propargyl alcohol

pyrrolidine

→

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

المردود 94.9%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىwas purged with argon
2. 2
   ترشيحThe reaction mixture was filtered through
3. 3
   أخرىto remove solids
4. 4
   غسيلThe filter agent was rinsed with EtOAc
5. 5
   استخلاصthe filtrate was extracted with EtOAc (3×75 mL)
6. 6
   غسيلThe combined extracts were washed with water and brine
7. 7
   تجفيفdried over anhyd Na2SO4
8. 8
   تركيزconcentrated
9. 9
   أخرىpurified by flash chromatography (80% EtOAc/hexanes)

الإجراء التجريبي

A mixture of 2-(4-bromo-2,6-difluorobenzylthio)-5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole (0.79 g, 1.35 mmol), propargyl alcohol (122 μL, 2.03 mmol), pyrrolidine (169 μL, 2.03 mmol), CuI (26 mg, 0.13 mmol) and PdCl2(dppf)2 (50 mg, 0.07 mmol) in DMF (6.80 mL) was purged with argon and then heated to 80° C. for 3 h. The reaction mixture was filtered through to remove solids. The filter agent was rinsed with EtOAc and the filtrate was extracted with EtOAc (3×75 mL). The combined extracts were washed with water and brine, dried over anhyd Na2SO4, concentrated and purified by flash chromatography (80% EtOAc/hexanes) to get 3-(4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorophenyl)prop-2-yn-1-ol (714 mg, 94%) as a yellow solid. MS (EI) m/z 557 (MH+).

المصدر