2-Nitroaniline → (2-Nitrophenyl)-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethyl}amine

HRID 244401Notes

Reaction equation

HRID 244401 reaction equation
[N+:1]([C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH2:6])([O-:3])=[O:2].[F:11][C:12]([F:32])([F:31])[C:13]([C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)[N:19]=[CH:18]2)=O.C(N(CC)CC)C.[BH4-].[Na+]>ClCCl.CO.[OH-].[Na+].Cl[Ti](Cl)(Cl)Cl>[N+:1]([C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH:6][CH:13]([C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([C:24]1[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=1)[N:19]=[CH:18]2)[C:12]([F:31])([F:11])[F:32])([O-:3])=[O:2]

Participants

9

Reactant 4

HCID 69462-NitroanilineHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 579432692,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone

Product 1

HCID 59437215(2-Nitrophenyl)-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethyl}amineYield 53%

Reagents, catalysts & solvents 4

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 134 mg (0.97 mmol) of 2-nitroaniline in 5 mL of dichloromethane was added 300 mg (0.97 mmol) of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]ethanone, 210 μL (2.9 mmol) of triethylamine, followed by 500 μL 0.5 mmol) of TiCl4. The mixture stirred for 20 hours and was then diluted with methanol followed by 40 mg (1.0 mmol) of sodium borohydride. After 1 hour, the mixture was diluted with 50 mL of 1N aqueous NaOH and extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude product was purified by Combiflash chromatography using EtOAc-hexanes (0-70% gradient) to afford 220 mg (53%) of the title compound as a yellow foam. MS m/z 431 (MH+).

Workup

  1. waitAfter 1 hour
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by Combiflash chromatography

Sources & evidence

ORD record
ord-d8d1e48177b546049e7f5b004783f78f
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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