HCID 59272956, compound → HCID 135910367, compound

HRID 2423106Notes

Reaction equation

HRID 2423106 reaction equation
[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

Participants

3

Reactant 1

HCID 59272956HCID 59272956, compound

Product 1

HCID 135910367HCID 135910367, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-93244fbac6b84eb1b7d15dceedc46e36
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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