Cesium carbonate → HCID 66742365, compound

HRID 1431161Notes

Reaction equation

HRID 1431161 reaction equation
C(C1C=C2C(=C(F)C=1)C(=O)N(C1C=CC=C(C3C=[C:27]([NH:29][C:30]4C=CC(C(N5CCC(O)C5)=O)=C[N:31]=4)[C:26](=O)[N:25]([CH3:45])N=3)C=1CO)N=C2)(C)(C)C.Br[C:49]1[C:50](=[O:57])[N:51]([CH3:56])[N:52]=[C:53]([Cl:55])[CH:54]=1.[C:58](=O)([O-])[O-].[Cs+].[Cs+].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.[O:106]1[CH2:111][CH2:110][O:109][CH2:108][CH2:107]1>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:55][C:53]1[CH:54]=[C:49]([NH:31][C:30]2[CH:45]=[N:25][C:26]([C@H:111]3[CH2:110][O:109][C:108]([CH3:107])([CH3:58])[O:106]3)=[CH:27][N:29]=2)[C:50](=[O:57])[N:51]([CH3:56])[N:52]=1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 56656267HCID 56656267, compoundHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 66742365HCID 66742365, compoundYield 50%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (S)-5-(2,2-dimethyl-1,3-dioxolan-4-yl)pyrazin-2-amine (prepared as in WO2004052869, Example 54, 175 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 (50 mL) 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 precipitate formed was isolated by filtration, washed with ether and dried under vacuum to give 6-chloro-4-[5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-pyrazin-2-ylamino]-2-methyl-2H-pyridazin-3-one (150 mg, 50%) 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 precipitate formed
  9. customwas isolated by filtration
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-1d80e18c598945799697ab488f3f0c79
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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