3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloroquinoline → (3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

HRID 1507312Notes

Reaction equation

HRID 1507312 reaction equation
[N:1]1(C2C=CC(CC3C(Cl)=NC4C(C=3Cl)=CC(Br)=CC=4)=CC=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[Cl:26][C:27]1[C:36]([CH2:37][C:38]2[CH:43]=[CH:42][C:41](S(C)(=O)=O)=[CH:40][CH:39]=2)=[C:35]([Cl:48])[C:34]2[C:29](=[C:30]([CH3:57])[CH:31]=[C:32]([C:49]([C:51]3[N:55]([CH3:56])[CH:54]=[N:53][CH:52]=3)=[O:50])[CH:33]=2)[N:28]=1>O=P(Cl)(Cl)Cl>[N:1]1([C:41]2[CH:42]=[CH:43][C:38]([CH2:37][C:36]3[C:27]([Cl:26])=[N:28][C:29]4[C:34]([C:35]=3[Cl:48])=[CH:33][C:32]([C:49]([C:51]3[N:55]([CH3:56])[CH:54]=[N:53][CH:52]=3)=[O:50])=[CH:31][C:30]=4[CH3:57])=[CH:39][CH:40]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

4

Reactant 2

HCID 867155943-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloroquinoline2×HCID 86715618(2,4-dichloro-8-methyl-3-(4-(methylsulfonyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone2×

Product 1

HCID 118005956(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
105 °C

Procedure

A heterogeneous mixture of 2-(4-(1H-pyrazol-1-yl)benzyl)malonic acid (2.42 g 9.29 mmol, Intermediate 4: step b), (4-amino-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone (2 g, 9.29 mmol, Intermediate 13: step c) and POCl3 (10 mL) was heated at 105° C. for 4 hours. The mixture was cooled to room temperature, concentrated to remove excess POCl3 and ice water was added. The mixture was treated with NH4OH (kept adding ice during addition) to a basic pH 8-9 and the aqueous was then extracted with DCM. The DCM extracts were dried (Na2SO4), evaporated in vacuo and chromatographed (DCM/EtOAc, gradient) to provide the crude product. Pure product was precipitated with MeOH, filtered and dried to provide the title compound as a yellow solid.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated
  3. customto remove excess POCl3 and ice water
  4. additionwas added
  5. additionThe mixture was treated with NH4OH (kept adding ice during addition) to a basic pH 8-9
  6. extractionthe aqueous was then extracted with DCM
  7. dry with materialThe DCM extracts were dried (Na2SO4)
  8. customevaporated in vacuo
  9. customchromatographed (DCM/EtOAc, gradient)
  10. customto provide the crude product
  11. customPure product was precipitated with MeOH
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-9dc96d5eaf5b4ab3bc763a0612918907
Source dataset
uspto-grants-2015_12
Patent number
US09221804B2

Reaction notes

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