Ethyl Acetate → 6-{1-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-vinyl}-quinoline

HRID 69198Notes

Reaction equation

HRID 69198 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[CH:18][CH:17]=[CH:16]4)=[CH2:12])=[CH:9][N:10]=2)[N:7]=1.[CH3:23][N:24]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[N:25]1.C([O-])([O-])=O.[K+].[K+].CCOC(C)=O>COCCOC.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:23][N:24]1[CH:28]=[C:27]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([C:11]([C:13]4[CH:14]=[C:15]5[C:20](=[CH:21][CH:22]=4)[N:19]=[CH:18][CH:17]=[CH:16]5)=[CH2:12])=[CH:9][N:10]=3)[N:7]=2)[CH:26]=[N:25]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57917453HCID 57917453, compound

Product 1

HCID 579174486-{1-[6-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-yl]-vinyl}-quinoline

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

6-[1-(6-Chloro-imidazo[1,2-b]pyridazin-3-yl)-vinyl]-quinoline (Example 154, 2.5 g, 8.15 mmol) was dissolved in DME (20 mL) under argon atm. 1-Methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (2.54 g, 12.22 mmol) was added, followed by 2 M K2CO3 (11 mL) and PdCl2(PPh3)2 (172 mg). The RM was stirred at 90° C. for 3 h. It was then taken into a mixture of EtOAc and brine and extracted. Organic phase was dried on Na2SO4. After evaporation of the solvent the crude was purified by column chromatography in silica gel with the eluent EtOAc/MeOH=9:1 then 4:1. The collected fractions containing product were concentrated and recrystallized from EtOAc/pentane. After a night drying under vacuo, the title compound was obtained as a beige powder (tR 3.65 min (conditions 3), MH+=353).

Workup

  1. extractionextracted
  2. customOrganic phase was dried on Na2SO4
  3. customAfter evaporation of the solvent the crude
  4. customwas purified by column chromatography in silica gel with the eluent EtOAc/MeOH=9:1
  5. additionThe collected fractions containing product
  6. concentrationwere concentrated
  7. customrecrystallized from EtOAc/pentane
  8. customAfter a night drying under vacuo

Sources & evidence

ORD record
ord-55d07577f2064f2e856a89e5cdb9b2fe
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

Loading…