4-Chloro-5-(2-methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazole → 3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)4-methoxy-phenylamine

HRID 540529Notes

Reaction equation

HRID 540529 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:12]=[C:11]([N+:13]([O-])=O)[CH:10]=[CH:9][C:8]=1[O:16][CH3:17]>CCO>[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:12]=[C:11]([NH2:13])[CH:10]=[CH:9][C:8]=1[O:16][CH3:17]

Participants

3

Reactant 1

HCID 231395374-Chloro-5-(2-methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazole

Product 1

HCID 231395183-(4-Chloro-2-methyl-2H-pyrazol-3-yl)4-methoxy-phenylamineYield 86%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

4-Chloro-5-(2-methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazole (2.27 g, 8.5 mmol) was dissolved in dry EtOH (150 mL) and heated to 75° C. The heated solution was then treated with Sn(II) chloride dihydrate (9.6 g, 42.5 mmol) and stirred at 75° C. After three hours, the reaction was found to be complete by TLC and LCMS. The solvent was removed under reduced pressure. The residue was subsequently diluted with EtOAc (100 mL) and 1N NaOH, neutralizing the reaction to a pH of approximately 6 or 7. The mix was then filtered through celite. The organic layer was separated, and the aqueous layer was extracted with EtOAc (2×50 mL). The organic layers were combined, dried over Na2SO4, filtered, and the solvent removed under reduced pressure. The residue was then purified by flash chromatography (Biotage, SiO2, Hexanes/EtOAc gradient elution) to afford 1.73 g (86%) of 3-(4-chloro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine as a light brown solid. LCMS m/z (%) 240 (M+H37Cl, 37), 238 (M+H35Cl, 100). 1H NMR (400 MHz, CDCl3) δ: 7.48 (s, 1H), 6.87 (d, J=8, 1H), 6.81 (dd, j=8, J=4, 1H), 6.63 (d, J=4, 1H), 3.72 (s, 3H), 3.70 (s, 3H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionThe residue was subsequently diluted with EtOAc (100 mL) and 1N NaOH
  3. customthe reaction to a pH of approximately 6 or 7
  4. filtrationThe mix was then filtered through celite
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent removed under reduced pressure
  10. customThe residue was then purified by flash chromatography (Biotage, SiO2, Hexanes/EtOAc gradient elution)

Sources & evidence

ORD record
ord-327ffbc90ccb4eb79a3b02c076079c2a
Source dataset
uspto-grants-2014_10
Patent number
US08871797B2

Reaction notes

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