Dichloromethane → 1-(3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-3-(4-chlorophenyl)urea

HRID 540526Notes

Reaction equation

HRID 540526 reaction equation
[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:16][C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[O:18])[CH:11]=[CH:12][C:13]=1[O:14]C.C(Cl)Cl.[Al+3].[Cl-].[Cl-].[Cl-]>>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:16][C:17]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=2)=[O:18])[CH:11]=[CH:12][C:13]=1[OH:14]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6451240Aluminum(III) ChlorideHCID 112475691-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-Chloro-phenyl)-urea

Product 1

HCID 1355074951-(3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-3-(4-chlorophenyl)urea

Procedure

To Compound 1 (see Example 1.16) in CH2Cl2 (1.170 g, 2.68 mmol) was added anhydrous AlCl3 (1.432 g, 10.74 mmol, 4.0 equiv.) slowly at 0° C., it was stirred under reflux overnight and then quenched with saturated NaHCO2. The mixture was extracted with EtOAc, the combined organic phase was washed with water and brine, dried over MgSO4, filtered and evaporated. It was first purified with SiO2 column chromatography (Eluent: EtOAc/Hexane=1/3 to 1/1) and the major fractions containing Compound 58 were then purified by HPLC. The pure fractions were neutralized with saturated NaHCO3, extracted with EtOAc and dried with anhydrous MgSO4. MgSO4 was filtered and the solvent was removed under vacuum to provide Compound 58 as a white solid. LCMS m/z (%)=421 (M+H79Br35Cl, 29), 423 (M+H81Br35Cl, 100), 425 (M+H81Br37Cl, 21). 1H NMR (400 MHz, acetone-d6) δ: 847 (s, 1H), 8.16 (s, 1H), 8.04 (s, 1H), 7.44 (d, J=8.9 Hz, 2H), 7.38-7.43 (m, 1H), 7.35 (s, 1H), 7.26 (d, J=2.6 Hz, 1H), 7.15 (d, J=8.9 Hz, 2H), 6.87 (d, J=8.8 Hz, 1H), 3.62 (s, 3H).

Workup

  1. temperatureunder reflux overnight
  2. customquenched with saturated NaHCO2
  3. extractionThe mixture was extracted with EtOAc
  4. washthe combined organic phase was washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customIt was first purified with SiO2 column chromatography (Eluent: EtOAc/Hexane=1/3 to 1/1)
  9. additionthe major fractions containing Compound 58
  10. customwere then purified by HPLC
  11. extractionextracted with EtOAc
  12. dry with materialdried with anhydrous MgSO4
  13. filtrationMgSO4 was filtered
  14. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-57af2837c588409e8c49f631e1e2d68b
Source dataset
uspto-grants-2014_10
Patent number
US08871797B2

Reaction notes

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