Hydrochloric Acid → 1-{3-Fluoro-4-[(phenylmethyl)oxy]phenyl}-4-hydroxy-1H-indazole-6-carbonitrile

HRID 2423066노트

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HRID 2423066 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]=[CH:17][C:16]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:15]([F:27])[CH:14]=1.[OH-:28].[K+].Cl>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].CC(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)C>[F:27][C:15]1[CH:14]=[C:13]([N:6]2[C:7]3[C:3](=[C:2]([OH:28])[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=3)[CH:4]=[N:5]2)[CH:18]=[CH:17][C:16]=1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

참가 물질

9

반응물 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 672446504-Bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazole-6-carbonitrile

생성물 1

HCID 1363814381-{3-Fluoro-4-[(phenylmethyl)oxy]phenyl}-4-hydroxy-1H-indazole-6-carbonitrile수율 67.5%

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

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온도
90 °C

실험 절차

To a solution of 4-bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indazole-6-carbonitrile (D5) (535 mg, 1.27 mmol) in dioxane (10 mL) and water (10 mL) was added potassium hydroxide (284 mg, 5.07 mmol). The reaction mixture was degassed with argon and then treated with bis(1,1-dimethylethyl)[2′,4′,6′-tris(1-methylethyl)-2-biphenylyl]phosphane (32 mg, 0.075 mmol) and tris(dibenzylideneacetone)dipalladium (0) (23 mg, 0.025 mmol). After heating at 90° C. for 1 hour, the mixture was allowed to cool to room temperature and then diluted with ethyl acetate and water. The pH was adjusted to 7 by the addition of 1M hydrochloric acid. 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 5-100% ethyl acetate in hexane to yield the title compound (D6) (308 mg).

후처리

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

출처 및 근거

ORD 기록
ord-393112c45bec483d9bc145c68df76fa6
출처 데이터셋
uspto-grants-2011_06
특허 번호
US07960563B2

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