HCID 59272956、化合物 → HCID 135910367、化合物

HRID 2423106ノート

反応式

HRID 2423106 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:26]C)=[C:6]2[C:10]=1[N:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17]CC3C=CC=CC=3)=[C:13]([F:25])[CH:12]=1)[N:8]=[CH:7]2>Br>[F:1][C:2]1[C:10]2[N:9]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([F:25])[CH:12]=3)[N:8]=[CH:7][C:6]=2[C:5]([OH:26])=[CH:4][CH:3]=1

参加物

3

反応物 1

HCID 59272956HCID 59272956、化合物

生成物 1

HCID 135910367HCID 135910367、化合物収率 23%

試薬・触媒・溶媒 1

HCID 260Hydrogen Bromide溶媒

反応条件

温度
120 °C

実験手順

7-Fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-(methyloxy)-1H-indazole (D27) (280 mg, 0.764 mmol) was dissolved in HBr (48% aq., 15 mL) and refluxed at 120° C. under argon. After 2 hours the mixture was partitioned between DCM (50 mL)/water (50 mL), the pH adjusted to 7 by addition of a 2M solution of NaOH and the layers separated. The aqueous phase was extracted with DCM (3×50 mL) and the combined organics were washed with brine (50 mL), separated and dried over MgSO4, filtered and concentrated in vacuo. The crude material (198 mg) was purified by flash chromatography (Biotage SP4) with a gradient of 0-100% Et2O in hexane. The isolated material (75 mg) was further purified by MDAP to afford 46 mg of the title compound (E13).

後処理

  1. customAfter 2 hours the mixture was partitioned between DCM (50 mL)/water (50 mL)
  2. additionthe pH adjusted to 7 by addition of a 2M solution of NaOH
  3. customthe layers separated
  4. extractionThe aqueous phase was extracted with DCM (3×50 mL)
  5. washthe combined organics were washed with brine (50 mL)
  6. customseparated
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material (198 mg) was purified by flash chromatography (Biotage SP4) with a gradient of 0-100% Et2O in hexane
  11. customThe isolated material (75 mg) was further purified by MDAP

出典と根拠

ORDレコード
ord-93244fbac6b84eb1b7d15dceedc46e36
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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