1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 6-chloro-4-(5-(4-ethylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

HRID 449714Notes

Reaction equation

HRID 449714 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH2:5][CH2:4]1)[CH3:2].Br[C:17]1[C:18](=[O:25])[N:19]([CH3:24])[N:20]=[C:21]([Cl:23])[CH:22]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.ClCCl.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:23][C:21]1[CH:22]=[C:17]([NH:15][C:12]2[CH:11]=[CH:10][C:9]([N:6]3[CH2:5][CH2:4][N:3]([CH2:1][CH3:2])[CH2:8][CH2:7]3)=[CH:14][N:13]=2)[C:18](=[O:25])[N:19]([CH3:24])[N:20]=1

Participants

8

Reactant 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 284115995-(4-Ethylpiperazin-1-yl)pyridin-2-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 585403656-chloro-4-(5-(4-ethylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-oneYield 44%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 5-(4-ethylpiperazin-1-yl)pyridin-2-amine (185 mg, 0.90 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (200 mg, 0.90 mmol) cesium carbonate (1.02 g, 3.13 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (77.7 mg, 0.13 mmol) in dioxane (10 ml) was flushed with argon before tris(dibenzylideneacetone)dipalladium(0) (61.5 mg, 0.07 mmol) was added and the resulting solution was heated at 90° C. for 18 h. The mixture was cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the aqueous layer was extracted with dichloromethane (2×25 mL). The organic layers were combined, dried over magnesium sulfate. The resulting mixture was filtered and concentrated in vacuo. The residue was triturated with methanol and dichloromethane and filtered, washed with ether and dried to give 6-chloro-4-[5-(4-ethyl-piperazin-1-yl)-pyridin-2-ylamino]-2-methyl-2H-pyridazin-3-one (138 mg, 44%) as a yellow solid.

Workup

  1. additionwas added
  2. temperatureThe mixture was cooled to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (2×25 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationThe resulting mixture was filtered
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated with methanol and dichloromethane
  9. filtrationfiltered
  10. washwashed with ether
  11. customdried

Sources & evidence

ORD record
ord-bb17a60d27ac42f9a895b6474403bb68
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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