Potassium Hydroxide → 1-{3,5-Difluoro-4-[(phenylmethyl)oxy]phenyl}-4-hydroxy-1H-indazole-6-carbonitrile

HRID 2423091노트

반응식

HRID 2423091 반응식
Br[C:2]1[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[C:13]1[CH:18]=[C:17]([F:19])[C:16]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:15]([F:28])[CH:14]=1.[OH-:29].[K+]>O1CCOCC1.O.C(OCC)(=O)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].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>[F:19][C:17]1[CH:18]=[C:13]([N:6]2[C:7]3[C:3](=[C:2]([OH:29])[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=3)[CH:4]=[N:5]2)[CH:14]=[C:15]([F:28])[C:16]=1[O:20][CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

참가 물질

8

반응물 2

HCID 14797Potassium HydroxideHCID 672458554-Bromo-1-{3,5-difluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazole-6-carbonitrile

생성물 1

HCID 1363814391-{3,5-Difluoro-4-[(phenylmethyl)oxy]phenyl}-4-hydroxy-1H-indazole-6-carbonitrile수율 76.6%

시약·촉매·용매 5

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane촉매HCID 962Water용매2회HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
90 °C

실험 절차

To a solution of 4-bromo-1-{3,5-difluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazole-6-carbonitrile (D36) (940 mg, 2.135 mmol) in dioxane (20 mL) and water (20 mL) was added potassium hydroxide (479 mg, 8.54 mmol). The mixture was degassed with argon and then treated with 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (54.4 mg, 0.128 mmol) and tris(dibenzylideneacetone)dipalladium(0) (39.1 mg, 0.043 mmol). The reaction mixture was heated to 90° C. for 1 hour. The reaction was diluted with ethyl acetate and water. After separation of the layers, the aqueous phase was re-extracted with ethyl acetate. The combined organic layers were dried over magnesium sulphate, filtered and concentrated in vacuo. The product was purified by silica gel chromatography eluting with 10-100% ethyl acetate in hexane to give the title compound (D37) (617 mg).

후처리

  1. customThe mixture was degassed with argon
  2. customAfter separation of the layers
  3. extractionthe aqueous phase was re-extracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by silica gel chromatography
  8. washeluting with 10-100% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-78dd4fc176ba4a7a8ba4c45a434dd3d8
출처 데이터셋
uspto-grants-2011_06
특허 번호
US07960563B2

반응 노트

불러오는 중…