Lithium Hydroxide → 4-(6-Bromo-5-(4-chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile

HRID 1661099Notes

Reaction equation

HRID 1661099 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][NH:11][C:10](=[O:14])[C:9]=2[C:15]2[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.O[Li].O.[Br:26]Br.[Li+].[OH-].[OH-].[Na+]>CO.O>[Br:26][C:13]1[C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)=[C:9]([C:15]2[CH:16]=[CH:17][C:18]([C:19]#[N:20])=[CH:21][CH:22]=2)[C:10](=[O:14])[NH:11][N:12]=1

Participants

8

Reactant 5

HCID 3939Lithium Hydroxide2×HCID 14798Sodium HydroxideHCID 24408Bromine4×HCID 168937Lithium hydroxide, monohydrate2×HCID 671292894-(5-(4-Chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile

Product 1

HCID 671286324-(6-Bromo-5-(4-chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrileYield 192.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent3×

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 4-(5-(4-chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile (10 g, 32.5 mmol) and LiOH.H2O (1.37 g, 32.65 mmol) in MeOH (200 mL) at 70° C. was added bromine (2.6 g, 16.26 mmol). The reaction mixture was stirred at 70° C. for 3 min. After this time, bromine (5.2 g, 32.5 mmol) and LiOH. H2O (2.74 g, 65.3 mmol) were added and the reaction mixture was stirred at 70° C. for an additional 3 min. After this time, another portion of bromine (2.6 g, 16.26 mmol) and LiOH.H2O (1.37 g, 32.65 mmol) was added and the reaction mixture was stirred for 3 min at 70° C. A final portion of bromine (2.6 g, 16.26 mmol) followed by LiOH. H2O (1.37 g, 32.65 mmol) was added and the reaction mixture was stirred at 70° C. for another 3 min. HPLC (Method A) showed disappearance of the starting material. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give a light yellow solid. This solid was diluted with water (100 mL) and the pH was adjusted to 7 with aq 1.0 N NaOH. The product was extracted with EtOAc (2×100 mL). The combined organic layer was washed with saturated NaCl, dried (MgSO4), filtered and the filtrate was concentrated to obtain 4-(6-bromo-5-(4-chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile as a pale yellow solid (12.1 g, 96%).

Workup

  1. stirringthe reaction mixture was stirred at 70° C. for an additional 3 min
  2. stirringthe reaction mixture was stirred for 3 min at 70° C
  3. stirringthe reaction mixture was stirred at 70° C. for another 3 min
  4. temperatureThe reaction mixture was cooled to room temperature
  5. concentrationconcentrated under reduced pressure
  6. customto give a light yellow solid
  7. extractionThe product was extracted with EtOAc (2×100 mL)
  8. washThe combined organic layer was washed with saturated NaCl
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-541db6214dd145bcb7de17d208bd8006
Source dataset
uspto-grants-2011_10
Patent number
US08030306B2

Reaction notes

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