Potassium Carbonate → 6-(2-Pyridylmethyl)-8-(3-chlorophenyl)-pyrido[2,3-d]pyridazin-5-one

HRID 861974Notes

Reaction equation

HRID 861974 reaction equation
[N+]([C:4]1[CH:5]=[C:6]([C:10]2[C:15]3[N:16]=[CH:17][CH:18]=[CH:19][C:14]=3[C:13](=O)[NH:12][N:11]=2)[CH:7]=[CH:8][CH:9]=1)([O-])=O.[H-].[Na+].[ClH:23].[N:24]1[CH:29]=[CH:28][C:27](CCl)=[CH:26][CH:25]=1.[C:32](=[O:35])([O-])[O-].[K+].[K+]>CN1CCCC1=O.C1(C)C=CC=CC=1>[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:13][N:12]1[C:32](=[O:35])[C:14]2[CH:19]=[CH:18][CH:17]=[N:16][C:15]=2[C:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([Cl:23])[CH:5]=2)=[N:11]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 745704-(Chloromethyl)pyridinium chlorideHCID 197007208-(3-Nitrophenyl) pyrido[2,3-d]pyridazin-5-one

Product 1

HCID 197006696-(2-Pyridylmethyl)-8-(3-chlorophenyl)-pyrido[2,3-d]pyridazin-5-one

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
55 °C

Procedure

8-(3-nitrophenyl)-pyrido[2,3-d]pyridazin-5-one (14.2 g, 55 mole) and sodium hydride (50% in oil, 2.7 g, 55 mole) were mixed in 150 mL of 1-methyl-2-pyrrolidone and the mixture was heated to 55° C. In a separatory funnel, 4-picolyl chloride hydrochloride (11 g, 67 mmoles), 50 mL of saturated potassium carbonate and 150 mL of toluene were mixed. After separation, the toluene solution was added to the reaction mixture dropwise over the period of 30 minutes. The mixture was heated to 60° C. for an additional 30 minutes, cooled to room temperature and poured into 300 mL of water. The mixture was extracted twice with ethyl acetate (500 mL). After drying the organic fraction with sodium sulfate (50 g), filtering and removal of the solvent the crude product was crystallized from isopropyl acetate (300 mL). The material was filtered and dried to yield 10.5 grams of 6-(2-pyridylmethyl)-8-(3-chlorophenyl)-pyrido[2,3-d]pyridazin-5-one. An additional 4.6 grams of the product was obtained as a second crop by concentration of the filtrates and filtering the resulting crystalline mass.

Workup

  1. customAfter separation
  2. additionthe toluene solution was added to the reaction mixture dropwise over the period of 30 minutes
  3. temperatureThe mixture was heated to 60° C. for an additional 30 minutes
  4. temperaturecooled to room temperature
  5. additionpoured into 300 mL of water
  6. extractionThe mixture was extracted twice with ethyl acetate (500 mL)
  7. dry with materialAfter drying the organic fraction with sodium sulfate (50 g)
  8. filtrationfiltering
  9. customremoval of the solvent the crude product
  10. customwas crystallized from isopropyl acetate (300 mL)
  11. filtrationThe material was filtered
  12. customdried

Sources & evidence

ORD record
ord-9d8ce3e7b11f4ca6bd1c94ac8d57a634
Source dataset
uspto-grants-1998_02
Patent number
US05716954

Reaction notes

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