Hydrochloric Acid → 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol dihydrochloride

HRID 220220Notes

Reaction equation

HRID 220220 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][CH2:21][OH:22])[N:15]=[CH:14]3)=[C:6]([CH:9]=1)[C:7]#[N:8].[ClH:23].[H][H]>[OH-].[OH-].[Pd+2].CCO>[ClH:23].[ClH:23].[NH2:8][CH2:7][C:6]1[CH:9]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][CH2:21][OH:22])[N:15]=[CH:14]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 445421215-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzonitrileHCID 178418361HCID 178418361, compound

Product 1

HCID 687815962-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)ethanol dihydrochlorideYield 96%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

A 2.5 L Parr reaction vessel was charged with 5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzonitrile (25.00 g, 84.09 mmol), EtOH (8.40 mL, 0.1M), and Pearlmans catalyst (5 g, 20% weight) and purged with nitrogen. Concentrated HCl (70.08 ml, 840.9 mmol) was added to the mixture. The vessel was charged with nitrogen gas (to 30 psi×3) and hydrogen (to 50 psi×3), and the reaction was stirred at ambient temperature for 66 hours. The mixture was filtered through a Celite pad and the pad was washed with EtOH. The filtrate was concentrated under reduced pressure, and the residue was azeotroped with EtOH and toluene to provide light brown solid to provide 30.2 g (96.0%) of the title compound. 1H NMR (400 MHz, CD3OD) δ 8.07 (s, 1H), 7.72 (d, J=8.61 Hz, 1H), 7.42 (d, J=2.35 Hz, 1H), 7.33 (dd, J=3.13 Hz, 8.61 Hz, 1H), 7.29 (dd, J=2.35 Hz, 8.61 Hz, 1H), 7.12 (dt, J=3.13 Hz, 8.61 Hz, 1H), 6.83 (dd, J=4.70 Hz, 8.61 Hz, 1H), 4.54 (t, J=5.48 Hz, 2H), 4.25 (br s, 2H), 3.98 (t, J=5.48 Hz, 2H).

Workup

  1. customA 2.5 L Parr reaction vessel
  2. custompurged with nitrogen
  3. filtrationThe mixture was filtered through a Celite pad
  4. washthe pad was washed with EtOH
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was azeotroped with EtOH and toluene
  7. customto provide light brown solid

Sources & evidence

ORD record
ord-04fb3317ece446f486a447a3931685bd
Source dataset
uspto-grants-2012_06
Patent number
US08202899B2

Reaction notes

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