Hydrochloric Acid → HCID 178505393, compound

HRID 1773223Notes

Reaction equation

HRID 1773223 reaction equation
[F:1][C:2]1[C:3]([CH2:13][NH:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[C:17]([C:26]([F:29])([F:28])[F:27])[CH:16]=2)=[CH:4][C:5]2[O:9][C:8]([C:10]#[N:11])=[CH:7][C:6]=2[CH:12]=1.[NH4+].[Cl-].[N-:32]=[N+:33]=[N-:34].[Na+].Cl>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[C:3]([CH2:13][NH:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:23])([F:25])[F:24])=[C:17]([C:26]([F:29])([F:27])[F:28])[CH:16]=2)=[CH:4][C:5]2[O:9][C:8]([C:10]3[NH:34][N:33]=[N:32][N:11]=3)=[CH:7][C:6]=2[CH:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 118452535HCID 118452535, compound

Product 1

HCID 178505393HCID 178505393, compoundYield 27.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 5-fluoro-6-(((4-(trifluoromethoxy)-3-(trifluoromethyl)phenyl)amino)methyl)-benzofuran-2-carbonitrile (637 mg, 1.523 mmol) in 15 mL DMF was added NH4Cl (326 mg, 6.09 mmol) and NaN3 (198 mg, 3.05 mmol). After the reaction mixture was stirred at room temperature overnight, the mixture was adjusted to pH=1 by addition of 1N HCl aqueous solution. The mixture was then diluted with AcOEt and washed with water, brine, dried over Na2SO4, and concentrated. The crude product was purified on basic HPLC (ammonium hydroxide modifier) 15-45% MeCN/Water to give N-((5-fluoro-2-(1H-tetrazol-5-yl)benzofuran-6-yl)methyl)-4-(trifluoromethoxy)-3-(trifluoromethyl)aniline (194 mg). LCMS retention time=1.41 minutes (LC method 1); MS (m+1)=462.1. 1H NMR (400 MHz, DMSO-d6) δ 4.50 (d, J=5.2 Hz, 2H), 6.93 (dd, J=9.2, 3.0 Hz, 1H), 7.00 (br. s., 1H), 7.05 (d, J=2.8 Hz, 1H), 7.33 (d, J=9.0 Hz, 1H), 7.61-7.69 (m, 2H), 7.75 (d, J=5.7 Hz, 1H).

Workup

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude product was purified on basic HPLC (ammonium hydroxide modifier) 15-45% MeCN/Water

Sources & evidence

ORD record
ord-ea13d6e5f17c4c61956eb066170d0eaa
Source dataset
uspto-grants-2016_02
Patent number
US09255093B2

Reaction notes

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