1,4-Dioxane → HCID 66743370, compound

HRID 1431202Notes

Reaction equation

HRID 1431202 reaction equation
C1C2(CN(C(C3C=CC([NH:16][C:17]4C(=O)[N:21](C)[N:20]=[C:19](C5C(CO)=C(N6N=CC7C(=C(F)C=C(C(C)(C)C)C=7)C6=O)C=CC=5)[CH:18]=4)=NC=3)=O)C2)CO1.Br[C:50]1[C:51](=[O:58])[N:52]([CH3:57])[N:53]=[C:54]([Cl:56])[CH:55]=1.C1(P(C2C=CC=CC=2)[C:66]2[C:79]3[O:78][C:77]4[C:72](=[CH:73]C=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)[C:70]=3C=CC=2)C=CC=CC=1.[O:101]1CCOCC1>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:56][C:54]1[CH:55]=[C:50]([NH:16][C:17]2[CH:18]=[CH:19][N:20]([CH2:73][C@@H:72]3[CH2:77][O:78][C:79]([CH3:70])([CH3:66])[O:101]3)[N:21]=2)[C:51](=[O:58])[N:52]([CH3:57])[N:53]=1

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 56656128HCID 56656128, compoundHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 66743370HCID 66743370, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (R)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine (prepared as in WO2009127546(A1), Example 49, 177 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, 0.134 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/dichloromethane) to give (R)-6-chloro-4-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-ylamino)-2-methylpyridazin-3(2H)-one (249 mg, 82%) 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
  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/dichloromethane)

Sources & evidence

ORD record
ord-f0898ce9cea84d65a68b0a693d972376
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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