Hydrochloric Acid → HCID 67135172, compound

HRID 2174633Notes

Reaction equation

HRID 2174633 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([F:10])[C:3]=1[C:11]1[C:12]([CH3:27])=[N:13][N:14]([CH3:26])[C:15]=1[O:16][C:17]1[C:22]([F:23])=[CH:21][C:20](N)=[CH:19][C:18]=1[F:25].N(OC(C)(C)C)=O.[ClH:35]>C(#N)C.[Cu]Cl>[Cl:35][C:20]1[CH:21]=[C:22]([F:23])[C:17]([O:16][C:15]2[N:14]([CH3:26])[N:13]=[C:12]([CH3:27])[C:11]=2[C:3]2[C:2]([F:1])=[CH:7][C:6]([O:8][CH3:9])=[CH:5][C:4]=2[F:10])=[C:18]([F:25])[CH:19]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 67135163HCID 67135163, compound

Product 1

HCID 67135172HCID 67135172, compound

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

Copper(I) chloride (56 mg, 0.42 mmol) was added to a solution of 4-[[4-(2,6-difluoro-4-methoxyphenyl)-1,3-dimethyl-1H-pyrazol-5-yl]oxy]-3,5-difluorobenzenamine (prepared analogous to Synthesis Example 9) (132 mg, 0.346 mmol) in acetonitrile (5 mL). The stirred mixture was cooled using an ice-water bath, and tert-butyl nitrite (90% technical grade, 72 μL) was added dropwise. The reaction mixture was allowed to warm slowly to ambient temperature and stirred at room temperature overnight, and then it was heated at reflux for 1 h. Hydrochloric acid (1 N, 5 mL) was added, and the mixture was extracted with ethyl acetate (˜20 mL). The organic phase was washed with brine, dried over MgSO4, and concentrated. The residue was purified by column chromatography through silica gel eluted with 20% ethyl acetate in hexane to give the title product, a compound of the present invention, as a viscous oil (45 mg).

Workup

  1. temperatureThe stirred mixture was cooled
  2. temperatureit was heated
  3. temperatureat reflux for 1 h
  4. extractionthe mixture was extracted with ethyl acetate (˜20 mL)
  5. washThe organic phase was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography through silica gel
  9. washeluted with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-da6cb53c605a401088ecae094b55c0a0
Source dataset
uspto-grants-2015_06
Patent number
US09062005B2

Reaction notes

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