Cesium carbonate → 6-Chloro-2-methyl-4-(5-((4-methylpiperazin-1-yl)methyl)pyridin-2-ylamino)pyridazin-3(2H)-one

HRID 449652Notes

Reaction equation

HRID 449652 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH2:4][CH2:3]1.Br[C:17]1[C:18](=[O:25])[N:19]([CH3:24])[N:20]=[C:21]([Cl:23])[CH:22]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>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:23][C:21]1[CH:22]=[C:17]([NH:15][C:12]2[CH:11]=[CH:10][C:9]([CH2:8][N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:14][N:13]=2)[C:18](=[O:25])[N:19]([CH3:24])[N:20]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 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 592929015-((4-Methylpiperazin-1-yl)methyl)pyridin-2-amine

Product 1

HCID 667423596-Chloro-2-methyl-4-(5-((4-methylpiperazin-1-yl)methyl)pyridin-2-ylamino)pyridazin-3(2H)-oneYield 50.9%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

5-((4-Methylpiperazin-1-yl)methyl)pyridin-2-amine (3.2 g, 15.5 mmol, Eq:1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (3.64 g, 16.3 mmol, Eq:1.05), xantphos (1.35 g, 2.33 mmol, Eq: 0.15) tris(dibenzylideneacetone)dipalladium (0) (1.07 g, 1.16 mmol, Eq: 0.075) and cesium carbonate (15.2 g, 46.5 mmol, Eq: 3.00) were added to a sealed tube under nitrogen. Dioxane (103 ml) was added and the solution was degassed with nitrogen. The tube was capped and heated at 110° C. overnight. The reaction mixture was filtered through celite and the cake was washed with DCM. 1M HCl was added to and the layers were separated. The aqueous layer was basified with 2M NaOH and extracted several times with DCM. Most of the solvent was evaporated and the residue was triturated with ether. The solid that formed was filtered and dried to give 2.75 g (50.8%) of product which was used without further purification.

Workup

  1. customthe solution was degassed with nitrogen
  2. customThe tube was capped
  3. filtrationThe reaction mixture was filtered through celite
  4. washthe cake was washed with DCM
  5. addition1M HCl was added to and the layers
  6. customwere separated
  7. extractionextracted several times with DCM
  8. customMost of the solvent was evaporated
  9. customthe residue was triturated with ether
  10. customThe solid that formed
  11. filtrationwas filtered
  12. customdried

Sources & evidence

ORD record
ord-42c3255932ff456cbb2f8c3a518e90c0
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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