Sodium Carbonate → 4-[6-(4-Fluorophenyl)imidazo[1,2-a]pyrimidin-7-yl]-benzaldehyde

HRID 1851151Notes

Reaction equation

HRID 1851151 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][N:5]2[CH:15]=[CH:16][N:17]=[C:4]2[N:3]=1.[CH:18]([C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1)=[O:19].C([O-])([O-])=O.[Na+].[Na+]>C(COC)OC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]2[C:2]([C:23]3[CH:24]=[CH:25][C:20]([CH:18]=[O:19])=[CH:21][CH:22]=3)=[N:3][C:4]3[N:5]([CH:15]=[CH:16][N:17]=3)[CH:6]=2)=[CH:9][CH:10]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 867030197-Chloro-6-(4-fluorophenyl)-imidazo[1,2-a]pyrimidine

Product 1

HCID 867030204-[6-(4-Fluorophenyl)imidazo[1,2-a]pyrimidin-7-yl]-benzaldehydeYield 42.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

2.8 g (11.3 mmol) 7-Chloro-6-(4-fluorophenyl)-imidazo[1,2-a]pyrimidine are given in 39 mL dimethoxyethane (not completely dissolved). 1.86 g (12.4 mmol) 4-formylphenylboronic acid and 22 mL Na2CO3 solution (10%) are added. After addition of 0.42 g (0.51 mmol) 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) the reaction mixture is purged 3× with argon and heated to 90° C. After 22 h stirring at 90° C. complete dissolution has taken place. The reaction mixture is cooled down and treated with 100 mL water and 150 mL dichloromethane. After vigorous stirring at rt for one hour the organic phase is separated. The aqueous phase is extracted twice with dichloromethane (100 mL each). The combined organic phases are washed twice with water (50 mL each), dried (Na2SO4) and the solvent is removed. The crude product is purified via chromatography (silicagel, dichloromethane/methanol). 1.52 g (42.4%) of the pure compound and two other fractions (224.6 mg=6.3% and 456.9 mg=12.7%) with contaminated product are obtained.

Workup

  1. dissolutioncompletely dissolved)
  2. customis purged 3× with argon
  3. dissolutioncomplete dissolution
  4. temperatureThe reaction mixture is cooled down
  5. additiontreated with 100 mL water and 150 mL dichloromethane
  6. stirringAfter vigorous stirring at rt for one hour the organic phase
  7. customis separated
  8. extractionThe aqueous phase is extracted twice with dichloromethane (100 mL each)
  9. washThe combined organic phases are washed twice with water (50 mL each)
  10. dry with materialdried (Na2SO4)
  11. customthe solvent is removed
  12. customThe crude product is purified via chromatography (silicagel, dichloromethane/methanol)

Sources & evidence

ORD record
ord-f79f735c9c8d4659b0414a2865d4dac8
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

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