Ethyl Acetate → 5,7-Difluoro-6-[6-(1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

HRID 69272Notes

Reaction equation

HRID 69272 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][C:12]3[C:13]([F:23])=[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(OC([N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]1)=O)(C)(C)C.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>[F:23][C:13]1[C:12]([CH2:11][C:8]2[N:6]3[N:7]=[C:2]([C:34]4[CH:35]=[N:31][NH:32][CH:33]=4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)=[C:21]([F:22])[CH:20]=[C:19]2[C:14]=1[CH:15]=[CH:16][CH:17]=[N:18]2

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 581475266-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-5,7-difluoro-quinoline

Product 1

HCID 1361394305,7-Difluoro-6-[6-(1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

6-(6-Chloro-imidazo[1,2-b]pyridazin-3-ylmethyl)-5,7-difluoro-quinoline (Stage 171.2, 100 mg, 0.299 mmol) was dissolved in DME (3 mL) under argon atm. 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (136 mg, 0.449 mmol) was added, followed by 2 M K2CO3 (0.40 mL) and PdCl2(PPh3)2 (10.5 mg, 0.015 mmol). The RM was stirred at 90° C. for 11 h. It was then taken into a mixture of EtOAc and brine and extracted. The combined organic phase was dried on Na2SO4. After evaporation of the solvent the crude was purified by flash chromatography in silica gel with the eluent DCM/MeOH=10:1. The collected fractions containing product were concentrated, dried under vacuo. The title compound was obtained as a white solid (tR 2.97 min (conditions 13), MH+=363).

Workup

  1. extractionextracted
  2. customThe combined organic phase was dried on Na2SO4
  3. customAfter evaporation of the solvent the crude
  4. customwas purified by flash chromatography in silica gel with the eluent DCM/MeOH=10:1
  5. additionThe collected fractions containing product
  6. concentrationwere concentrated
  7. customdried under vacuo

Sources & evidence

ORD record
ord-695231e686034f19ba5627800a05792f
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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