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

HRID 456155Notes

Reaction equation

HRID 456155 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% pure, 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 DMF was flashed 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 KF solution 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 which contains some triphenylphosphine oxide impurity and used in the next step without further purification (49 mg, 47%, 70% pure). LCMS (method A): [MH]+=334, tR=5.71 min.

Workup

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

Sources & evidence

ORD record
ord-25d70a6b75cb4d688b962609644a9746
Source dataset
uspto-grants-2013_07
Patent number
US08497368B2

Reaction notes

Loading…