Cesium carbonate → 6-Chloro-2-methyl-4-(pyrimidin-4-ylamino)pyridazin-3(2H)-one

HRID 1411955Notes

Reaction equation

HRID 1411955 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3][CH:2]=1.Br[C:9]1[C:10](=[O:17])[N:11]([CH3:16])[N:12]=[C:13]([Cl:15])[CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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].O1CCOCC1>[Cl:15][C:13]1[CH:14]=[C:9]([NH:7][C:4]2[CH:5]=[CH:6][N:1]=[CH:2][N:3]=2)[C:10](=[O:17])[N:11]([CH3:16])[N:12]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 689584-AminopyrimidineHCID 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-one

Product 1

HCID 666102376-Chloro-2-methyl-4-(pyrimidin-4-ylamino)pyridazin-3(2H)-oneYield 70%

Reagents, catalysts & solvents 2

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

Procedure

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (150 mL), pyrimidin-4-amine (1.7 g, 18.0 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (4.0 g, 18.0 mmol), and cesium carbonate (11.74 g, 36.0 mmol). After bubbling nitrogen through the suspension for 30 minutes, Xantphos (1.04 g, 1.8 mmol) and tris(dibenzylideneacetone)dipalladium(0) (823 mg, 0.9 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 15 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×50 mL). The combined filtrate was concentrated and the residue was washed with acetonitrile (5 mL) to afford 263a (2.99 g, 70%) as a yellow solid. MS: [M+H]+ 238

Workup

  1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 30 minutes
  3. customflush
  4. temperatureheated
  5. temperatureat reflux for 15 h
  6. filtrationfiltered
  7. washThe solid was washed with dichloromethane (2×50 mL)
  8. concentrationThe combined filtrate was concentrated
  9. washthe residue was washed with acetonitrile (5 mL)

Sources & evidence

ORD record
ord-cf84eee501ae419198e2775d11b156a9
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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