Hydrochloric Acid → 1-[3-(7-Fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]ethanone

HRID 1892317Notes

Reaction equation

HRID 1892317 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:19](=[CH:20][C:21]=3[F:22])[N:18]=[CH:17][CH:16]=[CH:15]4)=[CH:9][N:10]=2)[N:7]=1.C([Sn](CCCC)(CCCC)[C:28]([O:30]CC)=[CH2:29])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:22][C:21]1[CH:20]=[C:19]2[C:14]([CH:15]=[CH:16][CH:17]=[N:18]2)=[CH:13][C:12]=1[CH2:11][C:8]1[N:6]2[N:7]=[C:2]([C:28](=[O:30])[CH3:29])[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 581475166-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-7-fluoro-quinoline

Product 1

HCID 581905991-[3-(7-Fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]ethanoneYield 80.8%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a flask loaded with tetrakis-(triphenylphosphine)-palladium (1.7 g, 1.48 mmol) under nitrogen was added a solution of 6-(6-chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-7-fluoro-quinoline (5.8 g, 18.55 mmol) in DMF (150 mL). The system was purged with nitrogen three times and then tributyl-(1-ethoxy-vinyl)-stannane (6.59 mL, 19.47 mmol) was added. The temperature was increased to 100° C. and stirred overnight. After cooling, 20 mL of 3N HCl was added and the mixture was stirred for additional 2 h. Water was added and the product was then extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography to afford 4.8 g (79%) of the title compound as a dark yellow solid. 1H-NMR (400 MHz, MeOH-d4) δ ppm 8.82 (dd, 1H), 8.31 (d, 1H), 8.10 (d, 1H), 7.98 (d, 1H), 7.85 (s, 1H), 7.78 (d, 1H), 7.72 (d, 1H), 7.50 (q, 1H), 4.72 (s, 2H), 2.68 (S, 3H). LCMS (method A): [MH]+=321, tR=5.07 min.

Workup

  1. customThe system was purged with nitrogen three times
  2. temperatureAfter cooling
  3. stirringthe mixture was stirred for additional 2 h
  4. extractionthe product was then extracted with EtOAc
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-f66e11e5e66f4c899876578f57c9b1f8
Source dataset
uspto-grants-2013_08
Patent number
US08507676B2

Reaction notes

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