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

HRID 919441Notes

Reaction equation

HRID 919441 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 NaHCO3. 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, 69), 423 (M+H81Br35Cl, 100), 425 (M+H81Br37Cl, 21). 1H NMR (400 MHz, acetone-d6) δ: 8.47 (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 NaHCO3
  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-44f48abcb0614fda8034abd56e16df43
Source dataset
uspto-grants-2016_03
Patent number
US09273035B2

Reaction notes

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