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

HRID 456063Notes

Reaction equation

HRID 456063 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

A flask was charged with tetrakis-(triphenylphosphine)-palladium (1.7 g, 1.48 mmol) under nitrogen. 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) was added. The flask was purged with nitrogen gas three times and tributyl-(1-ethoxy-vinyl)-stannane (6.59 ml, 19.47 mmol) was added. The temperature was increased to 100° C. and stirred overnight. The reaction mixture was cooled to room temperature, 20 ml of 3N HCl was added and the mixture was stirred for additional 2 hrs. Water was added and the product was then extracted with EtOAc, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography to afford 4.8 g (yield: 79%) 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. additionwas added
  2. temperatureThe reaction mixture was cooled to room temperature
  3. stirringthe mixture was stirred for additional 2 hrs
  4. extractionthe product was then extracted with EtOAc
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-e3b906254b0f437db2dc1e6743aa3c66
Source dataset
uspto-grants-2013_07
Patent number
US08497368B2

Reaction notes

Loading…