反应详情

温度

70 °C

2-[3-(3-Chloro-4-fluorophenyl)-8-fluoroimidazo[1,2-α]pyridin-7-yl]-propan-2-ol, 4acetylbenzeneboronic acid and potassium phosphate were placed in a dry tube with 1,4dioxane/water (3:1) and this was heated to 70° C. under nitrogen. Tris(dibenzylideneacetone)dipalladium(0), tri-tert-butylphosphine (0.2M in 1,4dioxane) and 1,4-dioxane (0.5 ml) were mixed in a vial, and this mixture was added to the hot reaction via syringe. The resulting reaction mixture was heated at 70° C. for 12 h. The reaction was allowed to cool to room temperature then partitioned between dichloromethane and 2N hydrochloric acid. The aqueous layer was filtered through glass microfibre filter paper and evaporated to dryness. The residue was dissolved in methanol and evaporated to dryness. The residue was dissolved in dimethylsulfoxide (˜25 mg/ml), filtered through glass microfibre filter paper and purified by LC-MS. Appropriate fractions were combined and evaporated to give 1-{2′-fluoro-5′-[8-fluoro-7-(1-hydroxy-1-methylethyl)imidazo[1,2-α]pyridin-3-yl]biphenyl-4-yl}ethanone as an off-white solid (6 mg, 5%); m/z (ES+) 407 [MH+].

1. additionwas added to the hot reaction via syringe
2. customThe resulting reaction mixture
3. temperaturewas heated at 70° C. for 12 h
4. temperatureto cool to room temperature
5. customthen partitioned between dichloromethane and 2N hydrochloric acid
6. filtrationThe aqueous layer was filtered through glass microfibre
7. filtrationfilter paper
8. customevaporated to dryness
9. dissolutionThe residue was dissolved in methanol
10. customevaporated to dryness
11. dissolutionThe residue was dissolved in dimethylsulfoxide (˜25 mg/ml)
12. filtrationfiltered through glass microfibre
13. filtrationfilter paper
14. custompurified by LC-MS
15. customevaporated