Potassium Iodide → 3-(2-chloro-6-fluorophenyl)-1-(4-iodo-3-methoxyphenyl)-1H-1,2,4-triazol-5(4H)-one

HRID 508772Notes

Reaction equation

HRID 508772 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[NH:11][C:10]([C:14]3[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:21])=[N:9]2)=[CH:4][C:3]=1[O:22][CH3:23].CC1C=CC(S(O)(=O)=O)=CC=1.[I-:35].[K+].N([O-])=O.[Na+]>C(#N)C>[Cl:21][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]([F:20])[C:14]=1[C:10]1[NH:11][C:12](=[O:13])[N:8]([C:5]2[CH:6]=[CH:7][C:2]([I:35])=[C:3]([O:22][CH3:23])[CH:4]=2)[N:9]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 6101p-Toluenesulfonic acidHCID 23668193Sodium NitriteHCID 1364924321-(4-amino-3-methoxyphenyl)-3-(2-chloro-6-fluorophenyl)-1H-1,2,4-triazol-5(4H)-one

Product 1

HCID 1364924973-(2-chloro-6-fluorophenyl)-1-(4-iodo-3-methoxyphenyl)-1H-1,2,4-triazol-5(4H)-oneYield 54.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-(4-amino-3-methoxyphenyl)-3-(2-chloro-6-fluorophenyl)-1H-1,2,4-triazol-5(4H)-one (0.280 g, 0.83 mmol) in acetonitrile (5.0 ml) was added PTSA (0.477 g, 2.51 mmol). The reaction mass was stirred at RT for 1 h followed by addition of potassium iodide (0.347 g, 2.0 mmol) and sodium nitrite (0.115 g, 1.67 mmol) at 0-5° C. and further stirred for 2 h. Excess solvent was removed under vacuum and the residue reaction mass was quenched in water and extracted with ethyl acetate. The organic layer was washed with sodium metabisulphate and concentrated to obtain a crude product, which was further purified by column chromatography on silica gel eluting with 10% EtOAc: pet. ether to afford 0.200 g of desired product. 1H NMR (300 MHz, DMSO d6): δ 3.85 (s, 3H), 7.40 (d, J=8.7 Hz, 1H), 7.46-7.74 (m, 4H), 7.83 (d, J=8.1 Hz, 1H), 12.71 (br s, 1H); MS (m/z): 445.84 (M+H)+.

Workup

  1. stirringfurther stirred for 2 h
  2. customExcess solvent was removed under vacuum
  3. customthe residue reaction mass
  4. customwas quenched in water
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with sodium metabisulphate
  7. concentrationconcentrated
  8. customto obtain a crude product, which
  9. customwas further purified by column chromatography on silica gel eluting with 10% EtOAc

Sources & evidence

ORD record
ord-ae258d986d644d5a85b464fc71fe577b
Source dataset
uspto-grants-2015_08
Patent number
US09096545B2

Reaction notes

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