Sodium Chloride → 3-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazine

HRID 469191Notes

Reaction equation

HRID 469191 reaction equation
O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl:10][C:11]1[N:12]=[N:13][C:14](I)=[CH:15][CH:16]=1.[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[Na+]>CC[N+](CC1C=CC=CC=1)(CC)CC.[Cl-].C([O-])(=O)C.C([O-])(=O)C.[Pd+2].O.C1COCC1>[Cl:10][C:11]1[N:12]=[N:13][C:14]([C:22]2[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=2)=[CH:15][CH:16]=1

Participants

10

Reactant 5

HCID 5234Sodium ChlorideHCID 11776TriphenylphosphineHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 154188393-Chloro-6-iodopyridazineHCID 22031701Potassium phosphate, tribasic, monohydrate

Product 1

HCID 545956073-Chloro-6-(1-methyl-1H-pyrazol-4-yl)pyridazineYield 82%

Reagents, catalysts & solvents 4

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Water (253 mL) and THF (842 mL) were put in the reaction balloon. The reagents were added one by one to the stirred reaction mixture: potassium phosphate monohydrate 86.2 g (374 mmol) and BTEAC 2.25 g (9.88 mmol). Then 3-chloro-6-iodopyridazine, 45 g (187.2 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole, 46.73 g (224.6 mmol) were added and finally triphenylphosphine, 1.96 g (7.49 mmol) and palladiumdiacetate, 420 mg (1.87 mmol) were added. The reaction mixture was heated at 65° C. for 16 h. The reaction mixture was allowed to cool to 60° C. Then 935 mL water and 301.5 g sodium chloride were added. The mixture was stirred for 15 minutes and allowed to cool to 45° C. The phases were separated and the organic layer was washed with a solution of 45 g sodium chloride in 374 mL water. The organic layer was separated and stirred with magnesium sulphate (225 g) and charcoal (4.5 g). The mixture was filtered and evaporated. The evaporation residue was co-evaporated with toluene twice and evaporated further till a final volume of 200 ml. This residue was stirred for 16 h at room temperature. The resulting solids were collected by filtration. The solids were dried at reduced pressure affording 29.7 g of the title compound (152.6 mmol, yield 82%).

Workup

  1. additionThe reagents were added one by one
  2. customto the stirred reaction mixture
  3. temperatureto cool to 60° C
  4. temperatureto cool to 45° C
  5. customThe phases were separated
  6. washthe organic layer was washed with a solution of 45 g sodium chloride in 374 mL water
  7. customThe organic layer was separated
  8. stirringstirred with magnesium sulphate (225 g) and charcoal (4.5 g)
  9. filtrationThe mixture was filtered
  10. customevaporated
  11. customevaporated further till a final volume of 200 ml
  12. stirringThis residue was stirred for 16 h at room temperature
  13. filtrationThe resulting solids were collected by filtration
  14. customThe solids were dried at reduced pressure

Sources & evidence

ORD record
ord-0115d2961bff4e269c57c51c6e195916
Source dataset
uspto-grants-2014_01
Patent number
US08629144B2

Reaction notes

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