1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 66742961, compound

HRID 1431208Notes

Reaction equation

HRID 1431208 reaction equation
[NH2:1][C:2]1[CH:6]=[CH:5][N:4]([CH2:7][C:8]([CH3:11])([OH:10])[CH3:9])[N:3]=1.Br[C:13]1[C:14](=[O:21])[N:15]([CH3:20])[N:16]=[C:17]([Cl:19])[CH:18]=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:19][C:17]1[CH:18]=[C:13]([NH:1][C:2]2[CH:6]=[CH:5][N:4]([CH2:7][C:8]([OH:10])([CH3:11])[CH3:9])[N:3]=2)[C:14](=[O:21])[N:15]([CH3:20])[N:16]=1

Participants

8

Reactant 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-oneHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-ol

Product 1

HCID 66742961HCID 66742961, compoundYield 59%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
90 °C

Procedure

A solution of 1-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-ol (prepared as in U.S. Pat. No. 7,935,699 B2, Example 74, 139 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. The organic layers were combined, dried over magnesium sulfate. The resulting mixture was filtered and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 24 g, 0% to 10% methanol in dichloromethane) to give 6-chloro-4-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-ylamino]-2-methyl-2H-pyridazin-3-one (156 mg, 59%) as a light 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
  5. dry with materialdried over magnesium sulfate
  6. filtrationThe resulting mixture was filtered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (silica gel, 24 g, 0% to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-3930f84ec844467ebe248fcd905d6c0c
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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