Ammonium Chloride → N-((2-(2H-tetrazol-5-yl)benzofuran-6-yl)methyl)-3-bromo-4-(trifluoromethoxy)aniline

HRID 1773217Notes

Reaction equation

HRID 1773217 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:13][CH2:14][C:15]2[CH:25]=[CH:24][C:18]3[CH:19]=[C:20]([C:22]#[N:23])[O:21][C:17]=3[CH:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].[N-:26]=[N+:27]=[N-:28].[Na+].[Cl-].[NH4+]>CN(C=O)C.O>[N:23]1[NH:26][N:27]=[N:28][C:22]=1[C:20]1[O:21][C:17]2[CH:16]=[C:15]([CH2:14][NH:13][C:4]3[CH:5]=[CH:6][C:7]([O:8][C:9]([F:10])([F:11])[F:12])=[C:2]([Br:1])[CH:3]=3)[CH:25]=[CH:24][C:18]=2[CH:19]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 1184525066-(((3-Bromo-4-(trifluoromethoxy)phenyl)amino)methyl)benzofuran-2-carbonitrile

Product 1

HCID 118452529N-((2-(2H-tetrazol-5-yl)benzofuran-6-yl)methyl)-3-bromo-4-(trifluoromethoxy)anilineYield 57.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

6-(((3-bromo-4-(trifluoromethoxy)phenyl)amino)methyl)benzofuran-2-carbonitrile (651 mg, 1.58 mmol), sodium azide (0.12 g, 1.90 mmol) and ammonium chloride (0.10 g, 1.90 mmol) were dissolved in DMF (15.84 ml). The mixture was stirred at RT for 18 hr. After 18 hr the r×n was not complete and the reaction was heated to 50° C. for 2 hr. The reaction was cooled to RT and diluted with water (pH˜1). The crude material was extracted from the diluted aqueous pH=1 layer three times with a 10% MeOH/90% EtOAc mixture. The combined organic layers were washed 5× with pH=1 water to remove DMF and sodium azide, they were then washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude mixture was purified on basic HPLC (ammonium hydroxide modifier) 15-40% MeCN/Water to give N-((2-(2H-tetrazol-5-yl)benzofuran-6-yl)methyl)-3-bromo-4-(trifluoromethoxy)aniline (413 mg). LCMS retention time=1.35 minutes (LC method 1); MS (m+1)=454.2. 1H NMR (400 MHz, DMSO-d6) δ 4.39 (d, J=5.8 Hz, 2H), 6.66 (dd, J=9.0, 2.8 Hz, 1H), 6.83 (t, J=5.9 Hz, 1H), 6.93 (d, J=2.7 Hz, 1H), 7.08 (d, J=0.9 Hz, 1H), 7.17 (dd, J=9.2, 1.1 Hz, 1H), 7.25 (dd, J=8.0, 1.3 Hz, 1H), 7.54-7.64 (m, 2H).

Workup

  1. waitAfter 18 hr the r×n was not
  2. temperaturecomplete and the reaction was heated to 50° C. for 2 hr
  3. temperatureThe reaction was cooled to RT
  4. extractionThe crude material was extracted from the diluted aqueous pH=1 layer three times with a 10% MeOH/90% EtOAc mixture
  5. washThe combined organic layers were washed 5× with pH=1 water
  6. customto remove DMF and sodium azide, they
  7. washwere then washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude mixture was purified on basic HPLC (ammonium hydroxide modifier) 15-40% MeCN/Water

Sources & evidence

ORD record
ord-116713791e21474b9fefa1df94c6b569
Source dataset
uspto-grants-2016_02
Patent number
US09255093B2

Reaction notes

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