Hydrochloric Acid → 1-(3-(1-(7-Fluoroquinolin-6-yl)-1-hydroxyethyl)imidazo[1,2-b]pyridazin-6-yl)ethanone

HRID 456084Notes

Reaction equation

HRID 456084 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:14]3[CH:15]=[C:16]4[C:21](=[CH:22][C:23]=3[F:24])[N:20]=[CH:19][CH:18]=[CH:17]4)([OH:13])[CH3:12])=[CH:9][N:10]=2)[N:7]=1.C([Sn](CCCC)(CCCC)[C:30]([O:32]CC)=[CH2:31])CCC.Cl.O>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:24][C:23]1[CH:22]=[C:21]2[C:16]([CH:17]=[CH:18][CH:19]=[N:20]2)=[CH:15][C:14]=1[C:11]([C:8]1[N:6]2[N:7]=[C:2]([C:30](=[O:32])[CH3:31])[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1)([OH:13])[CH3:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 581475421-(6-Chloroimidazo[1,2-b]pyridazin-3-yl)-1-(7-fluoroquinolin-6-yl)ethanol

Product 1

HCID 669270341-(3-(1-(7-Fluoroquinolin-6-yl)-1-hydroxyethyl)imidazo[1,2-b]pyridazin-6-yl)ethanoneYield 45.4%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

In a flask was charged with tetrakis-(triphenylphosphine)-palladium (51 mg, 0.044 mmol) under nitrogen. A solution of 1-(6-chloroimidazo[1,2-b]pyridazin-3-yl)-1-(7-fluoroquinolin-6-yl)ethanol (150 mg, 0.44 mmol) in DMF (10 mL) was added. The system was purged with nitrogen gas three times and tributyl-(1-ethoxy-vinyl)-stannane (0.16 ml, 0.46 mmol) was added. The temperature was increased to 100° C. and stirred overnight. The reaction mixture was cooled to room temperature, 3N HCl was added and the mixture was stirred for additional 4 hrs. Water was added and the mixture was then extracted with EtOAc, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (3% to 10% MeOH in CH2Cl2) to afford 70 mg (yield: 41%) title compound. LCMS (method B): [MH]+=351, tR=2.01 min.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringthe mixture was stirred for additional 4 hrs
  4. extractionthe mixture was then extracted with EtOAc
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (3% to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-0fd31b68f6454611abdcd2f1729df609
Source dataset
uspto-grants-2013_07
Patent number
US08497368B2

Reaction notes

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