tert-Butanol → 1-Methyl-5-phenoxy-1H-pyrazol-4-ylamine

HRID 1485029Notes

Reaction equation

HRID 1485029 reaction equation
[CH3:1][N:2]1[C:6]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:5](C(O)=O)[CH:4]=[N:3]1.CC(O)(C)C.CC[N:24](C(C)C)C(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>O1CCOCC1>[CH3:1][N:2]1[C:6]([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:5]([NH2:24])[CH:4]=[N:3]1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 84016145HCID 84016145, compound

Product 1

HCID 867185511-Methyl-5-phenoxy-1H-pyrazol-4-ylamine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred mixture of 1-Methyl-5-phenoxy-1H-pyrazole-4-carboxylic acid (16.00 g; 73.32 mmol), t-BuOH (51.20 g; 690.77 mmol) in 1,4-dioxane under argon was added DIPEA (37.44 g; 289.69 mmol) and Diphenylphosphoryl azide (41.60 g; 151.16 mmol). After 10 minutes at ambient temperature it was heated up to 110° C. and stirred there for 3 hours. The solvent was evaporated and the crude material purified by column chromatography. This compound was dissolved in DCM and treated with 4 M HCl in 1,4-dioxane. It was stirred for 2 days at ambient temperature. The solvent was evaporated and the residue dissolved in water and washed with EtOAc. The aqueous layer was basified with NaHCO3 solution and extracted with EtOAc. The organic layer was dried and concentrated to dryness.

Workup

  1. customThe solvent was evaporated
  2. customthe crude material purified by column chromatography
  3. dissolutionThis compound was dissolved in DCM
  4. additiontreated with 4 M HCl in 1,4-dioxane
  5. stirringIt was stirred for 2 days at ambient temperature
  6. customThe solvent was evaporated
  7. dissolutionthe residue dissolved in water
  8. washwashed with EtOAc
  9. extractionextracted with EtOAc
  10. customThe organic layer was dried
  11. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-6d06588e089b4ce29141096132a74d9d
Source dataset
uspto-grants-2016_08
Patent number
US09422290B2

Reaction notes

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