Sulfuric Acid → 2-Chloro-6-propylimidazo[1,2-b]pyridazine

HRID 1685967Notes

Reaction equation

HRID 1685967 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7](Cl)=[N:6][N:5]2[CH:11]=1.[C:12]1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)[CH:17]=CC=C[CH:13]=1.C([Mg]Br)CC.S(=O)(=O)(O)O>[Ni].C1C=C2C(C=C(C([O-])=O)C=C2)=CC=1.C1C=C2C(C=C(C([O-])=O)C=C2)=CC=1.[Ni+2].O1CCCC1.C1(C)C(C)=CC=CC=1.C1(C)C=CC=CC=1>[CH2:13]([C:7]1[CH:8]=[CH:9][C:4]2[N:5]([CH:11]=[C:2]([Cl:1])[N:3]=2)[N:6]=1)[CH2:12][CH3:17]

Participants

10

Reactant 4

HCID 1118Sulfuric AcidHCID 812191,3-Bis(diphenylphosphino)propaneHCID 144223582,6-Dichloroimidazo[1,2-b]pyridazine2×HCID 178455851HCID 178455851, compound

Product 1

HCID 230280952-Chloro-6-propylimidazo[1,2-b]pyridazineYield 94%

Reagents, catalysts & solvents 5

HCID 935NickelCatalyst2×HCID 14647680Nickel naphthenateCatalystHCID 1140TolueneSolventHCID 7237O-XyleneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Into a 500 mL four-necked separable flask purged with nitrogen, 20.17 g of 2,6-dichloroimidazo[1,2-b]pyridazine (content: 99.2% by weight) and 190.5 g of xylene were charged to prepare a xylene solution containing 2,6-dichloroimidazo[1,2-b]pyridazine. The solution obtained by mixing 4 mL of xylene and 0.22 g of 1,3-bis(diphenylphosphino)propane and 0.62 g of a toluene solution of nickel naphthenate (II) (content: 5% by weight) were mixed to prepare a solution containing a nickel catalyst. The xylene solution containing 2,6-dichloroimidazo[1,2-b]pyridazine and the solution containing a nickel catalyst were mixed, and to the resultant mixture, 63.4 g of a tetrahydrofuran solution of n-propylmagnesium bromide (content: 22.2% by weight) was added dropwise over about 2 hours at an inner temperature of 20 to 30° C. to effect reaction. After completion of the reaction, the reaction mixture was added dropwise into a mixture of 40.4 g of 3% by weight aqueous sulfuric acid solution and 1 g of Radiolite (which was manufactured by Showa Chemical Industry Co., LTD.). After that, the resultant mixture was stirred and filtrated. The organic layer was separated from the filtrate obtained and washed twice with about 40 g of water. The organic layer after washing was concentrated to obtain 20.9 g of 6-n-propyl-2-chloroimidazo[1,2-b]pyridazine (purity: 93.2%). Yield: 94%

Workup

  1. customInto a 500 mL four-necked separable flask purged with nitrogen, 20.17 g of 2,6-dichloroimidazo[1,2-b]pyridazine (content: 99.2% by weight) and 190.5 g of xylene
  2. additionwere charged
  3. customto prepare a xylene solution
  4. customThe solution obtained
  5. additionwere mixed
  6. customto prepare a solution
  7. additionwere mixed
  8. customreaction
  9. customAfter completion of the reaction
  10. filtrationfiltrated
  11. customThe organic layer was separated from the filtrate
  12. customobtained
  13. washwashed twice with about 40 g of water
  14. washThe organic layer after washing
  15. concentrationwas concentrated

Sources & evidence

ORD record
ord-5782ac9474f0488b96fd5a6ae0979c35
Source dataset
uspto-grants-2012_04
Patent number
US08148524B2

Reaction notes

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