1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 6-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-((2-(trimethyl-silyl)ethoxy)methyl)pyridazin-3(2H)-one

HRID 872180Notes

Reaction equation

HRID 872180 reaction equation
Br[C:2]1[C:3](=[O:17])[N:4]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:18][N:19]1[C:23]([CH3:24])=[CH:22][C:21]([NH2:25])=[N:20]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.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:8][C:6]1[CH:7]=[C:2]([NH:25][C:21]2[CH:22]=[C:23]([CH3:24])[N:19]([CH3:18])[N:20]=2)[C:3](=[O:17])[N:4]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[N:5]=1

Participants

6

Reactant 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 70177471,5-dimethyl-1H-pyrazol-3-amineHCID 580441204-Bromo-6-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)pyridazin-3(2H)-one

Product 1

HCID 585403246-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-((2-(trimethyl-silyl)ethoxy)methyl)pyridazin-3(2H)-oneYield 72%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 4-bromo-6-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)pyridazin-3(2H)-one 110a (1.19 g, 3.50 mmol), 1,5-dimethyl-1H-pyrazol-3-amine (409 mg, 3.68 mmol), in 1,4-dioxane (20 mL) in a 100 mL single-neck round-bottomed flask was added desium darbonate (3.42 g, 10.5 mmol). The mixture was purged with ditrogen for 30 min. Tris(dibenzylideneacetone)dipalladium(0) (321 mg, 0.350 mmol) and 4,5-bis(diphenyl-phosphino)-9,9-dimethylxanthene (344 mg, 0.596 mmol) were then added. The flask was connected to a nitrogen-purged condenser and the mixture was refluxed under nitrogen for 18 h. The mixture was cooled to room temperature, and filtered. The filter cake was suspended in ethyl acetate (30 mL) and water (10 mL) and filtered through Celite®. The layers were separated. The combined organic layers were dried with anhydrous magnesium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure. The residue was purified on silica eluted with a gradient 0 to 50% ethyl acetate in eeptane to afford 6-chloro-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-2-((2-(trimethylsilyl)ethoxy)methyl)pyridazin-3(2H)-one 110b as a yellow solid (928 mg, 72%).

Workup

  1. customThe mixture was purged with ditrogen for 30 min
  2. custompurged condenser
  3. temperaturethe mixture was refluxed under nitrogen for 18 h
  4. filtrationfiltered
  5. filtrationwater (10 mL) and filtered through Celite®
  6. customThe layers were separated
  7. dry with materialThe combined organic layers were dried with anhydrous magnesium sulfate
  8. customThe drying agent was removed by filtration
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customThe residue was purified on silica
  11. washeluted with a gradient 0 to 50% ethyl acetate in eeptane

Sources & evidence

ORD record
ord-61249e37eab24e4d8c0759ea77867949
Source dataset
uspto-grants-2015_03
Patent number
US08975260B2

Reaction notes

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