Potassium Phosphate, Tribasic → 1-{2'-Fluoro-5'-[8-fluoro-7-(1-hydroxy-1-methylethyl)imidazo[1,2-alpha]pyridin-3-yl]biphenyl-4-yl}ethanone

HRID 1180269노트

반응식

HRID 1180269 반응식
Cl[C:2]1[CH:3]=[C:4]([C:9]2[N:13]3[CH:14]=[CH:15][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[C:17]([F:18])[C:12]3=[N:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[C:23]([C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1)(=[O:25])[CH3:24].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1.O1CCOCC1.O>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[N:13]3[CH:14]=[CH:15][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[C:17]([F:18])[C:12]3=[N:11][CH:10]=2)=[CH:3][C:2]=1[C:29]1[CH:30]=[CH:31][C:26]([C:23](=[O:25])[CH3:24])=[CH:27][CH:28]=1

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 37021224-Acetylphenylboronic acidHCID 674866802-[3-(3-Chloro-4-fluorophenyl)-8-fluoroimidazo[1,2-alpha]pyridin-7-yl]propan-2-ol

생성물 1

HCID 103412761-{2'-Fluoro-5'-[8-fluoro-7-(1-hydroxy-1-methylethyl)imidazo[1,2-alpha]pyridin-3-yl]biphenyl-4-yl}ethanone수율 5%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매HCID 218864351,4-Dioxane--water (1/1)용매

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온도
70 °C

실험 절차

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+].

후처리

  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

출처 및 근거

ORD 기록
ord-220a78023af24056808665fca52d7017
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07279580B2

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