Potassium Phosphate, Tribasic → 4-(2-Benzyl-5-(4-chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile

HRID 1865832Notes

Reaction equation

HRID 1865832 reaction equation
[CH2:1]([N:8]1[C:13](=[O:14])[C:12](Cl)=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)#[N:24].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]([C:28]2[CH:29]=[CH:30][C:25]([C:23]#[N:24])=[CH:26][CH:27]=2)=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343264-Cyanophenylboronic acidHCID 597166542-benzyl-4-chloro-5-(4-chlorophenyl)pyridazin-3(2H)-one

Product 1

HCID 690251454-(2-Benzyl-5-(4-chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrileYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a sealed tube was added 2-benzyl-4-chloro-5-(4-chlorophenyl)pyridazin-3(2H)-one (3.31 gm, 110.0 mmol), 4-cyanophenyl boronic acid (2.94 gm, 20 mmol), Pd(dppf)Cl2 dichloromethane complex (0.817 gm, 1.0 mmol), potassium phosphate (6.36 gm, 30 mmol) and THF (10 ml). The reaction solution was degassed with argon for 5 min and then sealed in a reaction tube. The reaction was then heated to 90° C. and keeped at this temperature for 4 hrs. The reaction was then cooled to rt and diluted with EtOAc (50 ml). The reaction mixture was then poured into a separatory funnel and the layers were separated. The organic layer was washed with water (20 ml) and saturated aqueous NaCl (20 ml). The organic layer was then slurried with MgSO4 to remove excess water, filtered and concentrated to give the crude product. The crude product was purified using an automated column chromatography system (ISCO, 330 gm silica gel) eluting with a gradient of 0-70% EtOAc/Hex to give 3.65 gm (92% yield) 4-(2-benzyl-5-(4-chlorophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile. HPLC retention time (method B) 3.81 min; LCMS (M+H)=398.0.

Workup

  1. customThe reaction solution was degassed with argon for 5 min
  2. customsealed in a reaction tube
  3. temperatureThe reaction was then cooled to rt
  4. additiondiluted with EtOAc (50 ml)
  5. additionThe reaction mixture was then poured into a separatory funnel
  6. customthe layers were separated
  7. washThe organic layer was washed with water (20 ml) and saturated aqueous NaCl (20 ml)
  8. customto remove excess water
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product
  12. customThe crude product was purified
  13. washeluting with a gradient of 0-70% EtOAc/Hex

Sources & evidence

ORD record
ord-092b3073789f4c548040066919de217f
Source dataset
uspto-grants-2009_12
Patent number
US07629342B2

Reaction notes

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