Potassium Carbonate → 5-(5-Amino-3-tert-butyl-pyrazol-1-yl)-2-fluoro-phenol

HRID 60627

반응식

HRID 60627 반응식
[C:1]([C:5]1[CH:9]=[C:8]([NH2:10])[NH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:12]1[CH:13]=[CH:14][C:15]([F:19])=[C:16]([OH:18])[CH:17]=1.C(=O)([O-])[O-].[K+].[K+].CN[C@H]1CCCC[C@@H]1NC>C1(C)C=CC=CC=1.CCOC(C)=O.O.[Cu]I>[NH2:10][C:8]1[N:7]([C:12]2[CH:13]=[CH:14][C:15]([F:19])=[C:16]([OH:18])[CH:17]=2)[N:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:9]=1

참가 물질

9

반응물 4

HCID 11430Potassium CarbonateHCID 183421Phenol, 5-bromo-2-fluoro-HCID 13822957(1S,2S)-(+)-N,N'-Dimethylcyclohexane-1,2-diamineHCID 178441179HCID 178441179, 화합물

생성물 1

HCID 1177294775-(5-Amino-3-tert-butyl-pyrazol-1-yl)-2-fluoro-phenol수율 70%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매2회HCID 962Water용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
150 °C

실험 절차

To a solution of 3-(tert-butyl)-1H-pyrazol-5-amine (1.00 g, 7.20 mmol) in toluene (13 mL) was added 5-bromo-2-fluorophenol (1.51 g, 7.90 mmol), potassium carbonate (2.08 g, 15.1 mmol), (1S,2S)—N,N′-bis-methyl-1,2-cyclohexane-diamine (0.20 g, 1.40 mmol) then copper (I) iodide (0.07 g, 0.36 mmol). The mixture was degassed then heated at 150° C. for 1 h using microwave irradiation. Another portion of copper (I) iodide (0.07 g, 0.36 mmol) was added and the reaction mixture heated at 150° C. for a further 1 h using microwave irradiation. The mixture was diluted with EtOAc and water and the phases separated. The aqueous layer was then extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give an impure solid. The residue was partitioned between DCM and water and the phases separated. The organic layer was evaporated in vacuo and the residue was purified by FCC, using 0-5% MeOH in DCM. Further purification by FCC, using 0-25% EtOAc in DCM, gave the title compound as an orange gum (1.25 g, 70%). LCMS (Method 3): Rt 2.33 min, m/z 250.3 [MH+].

후처리

  1. customThe mixture was degassed
  2. custommicrowave irradiation
  3. temperaturethe reaction mixture heated at 150° C. for a further 1 h
  4. custommicrowave irradiation
  5. customthe phases separated
  6. extractionThe aqueous layer was then extracted with EtOAc (2×)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customto give an impure solid
  12. customThe residue was partitioned between DCM and water
  13. customthe phases separated
  14. customThe organic layer was evaporated in vacuo
  15. customthe residue was purified by FCC
  16. customFurther purification by FCC

출처 및 근거

ORD 기록
ord-95f6bda1339647beb5249d396b41337a
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440974B2

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