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

HRID 2423066ノート

反応式

HRID 2423066 の反応式
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

参加物

9

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 5

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane触媒HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-393112c45bec483d9bc145c68df76fa6
出典データセット
uspto-grants-2011_06
特許番号
US07960563B2

反応ノート

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