Cesium carbonate → 2-Cyclopropyl-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol

HRID 1922156

반응식

HRID 1922156 반응식
Cl[C:2]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][CH:14]=2)=[C:10]([CH3:24])[C:9]2[C:8]([OH:25])=[CH:7][CH:6]=[C:5]([F:26])[C:4]=2[N:3]=1.[CH:27]1(B(O)O)[CH2:29][CH2:28]1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>O>[CH:27]1([C:2]2[C:11]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)=[C:10]([CH3:24])[C:9]3[C:8]([OH:25])=[CH:7][CH:6]=[C:5]([F:26])[C:4]=3[N:3]=2)[CH2:29][CH2:28]1

참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 2760897Cyclopropylboronic acidHCID 1363483602-Chloro-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol

생성물 1

HCID 1363483632-Cyclopropyl-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol수율 23.1%

시약·촉매·용매 1

HCID 962Water용매

반응 조건

온도
90 °C

실험 절차

A mixture of 2-chloro-8-fluoro-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-ol (0.26 g), cyclopropylboronic acid (0.12 g), caesium carbonate (0.92 g), dioxane (5.7 mL) and water (1.4 mL) was purged with argon, and then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.058 g). The mixture was heated at 90° C. for 3 hours, cooled to room temperature, neutralised with saturated aqueous ammonium chloride solution and extracted with ethyl acetate (3×20 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (5.0 mL), dried over magnesium sulfate and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (1:0 to 3:2 by volume) gave title compound as a yellow oil (0.061 g).

후처리

  1. customwas purged with argon
  2. additiontreated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.058 g)
  3. temperaturecooled to room temperature
  4. extractionextracted with ethyl acetate (3×20 mL)
  5. washThe combined extracts were washed with saturated aqueous sodium chloride solution (5.0 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customPurification of the residue by column chromatography on silica gel
  9. washeluting with a mixture of cyclohexane and ethyl acetate (1:0 to 3:2 by volume)

출처 및 근거

ORD 기록
ord-93f3a879bbeb413e9fa5b6837cd7e1b0
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173812B2

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