Stannane, tributyl(1-ethoxyethenyl)- → 6-(1-Ethoxy-vinyl)-3-(1-methyl-1H-indazol-5-ylmethyl)-imidazo[1,2-b]pyridazine

HRID 1892326Notes

Reaction equation

HRID 1892326 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[N:17]([CH3:21])[N:16]=[CH:15]4)=[CH:9][N:10]=2)[N:7]=1.C([Sn](CCCC)(CCCC)[C:27]([O:29][CH2:30][CH3:31])=[CH2:28])CCC>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:30]([O:29][C:27]([C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[N:17]([CH3:21])[N:16]=[CH:15]4)=[CH:9][N:10]=2)[N:7]=1)=[CH2:28])[CH3:31]

Participants

5

Reactant 2

HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 581905366-Chloro-3-((1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazine

Product 1

HCID 581904976-(1-Ethoxy-vinyl)-3-(1-methyl-1H-indazol-5-ylmethyl)-imidazo[1,2-b]pyridazine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 6-chloro-3-((1-methyl-1H-indazol-5-yl)methyl)imidazo[1,2-b]pyridazine (180.0 mg, 36% purity, 0.22 mmol), tributyl(1-ethoxyvinyl)stannane (94 mg, 0.26 mmol) and Pd(PPh3)4 (25.1 mg, 0.02 mmol) in 10 mL of DMF was flushed with nitrogen, then heated at 110° C. and stirred overnight. Solvent was removed under reduced pressure; the residue was diluted with DCM, washed sequentially with aqueous KF and water. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (DCM:MeOH=20:1) to give the title compound containing some triphenylphosphine oxide impurity but used in the next step without further purification (49 mg, 47%, 70% purity). LCMS (method A): [MH]+=334, tR=5.71 min.

Workup

  1. customwas flushed with nitrogen
  2. customSolvent was removed under reduced pressure
  3. additionthe residue was diluted with DCM
  4. washwashed sequentially with aqueous KF and water
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash chromatography (DCM:MeOH=20:1)

Sources & evidence

ORD record
ord-a2594d6001914c00b3576c13ef7e8d86
Source dataset
uspto-grants-2013_08
Patent number
US08507676B2

Reaction notes

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