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

HRID 1851154Notes

Reaction equation

HRID 1851154 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[F:14])=[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:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[C:7]1[C:2]([C:23]2[CH:24]=[CH:25][C:20]([CH:18]=[O:19])=[CH:21][CH:22]=2)=[N:3][C:4]2[N:5]([CH:15]=[CH:16][N:17]=2)[CH:6]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 867030217-Chloro-6-(2-fluorophenyl)-imidazo[1,2-a]pyrimidine

Product 1

HCID 867030224-[6-(2-Fluorophenyl)-imidazo[1,2-a]pyrimidin-7-yl]-benzaldehydeYield 47.6%

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

665 mg (2.68 mmol) 7-Chloro-6-(2-fluorophenyl)-imidazo[1,2-a]pyrimidine are given in 9.2 mL dimethoxyethane (not completely dissolved). 442.9 mg (2.95 mmol) 4-formylphenylboronic acid and 5.3 mL Na2CO3 solution (10%) are added. After addition of 98.6 mg (0.12 mmol) 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) the reaction mixture is purged 3× with argon and heated to 90° C. for 20 hours. The reaction mixture is cooled down and treated with 30 mL water and 150 mL dichloromethane. After vigorous stirring at rt for 90 minutes the organic phase is separated. The aqueous phase is extracted with dichloromethane (100 mL). The combined organic phases are washed with water (50 mL) and brine (50 mL) and dried (Na2SO4). The solvent is removed and the crude product purified via chromatography (silicagel, dichloromethane/methanol). 404.8 mg (47.5%) of the desired product (contaminated) are obtained.

Workup

  1. dissolutioncompletely dissolved)
  2. customis purged 3× with argon
  3. temperatureThe reaction mixture is cooled down
  4. additiontreated with 30 mL water and 150 mL dichloromethane
  5. customis separated
  6. extractionThe aqueous phase is extracted with dichloromethane (100 mL)
  7. washThe combined organic phases are washed with water (50 mL) and brine (50 mL)
  8. dry with materialdried (Na2SO4)
  9. customThe solvent is removed
  10. customthe crude product purified via chromatography (silicagel, dichloromethane/methanol)

Sources & evidence

ORD record
ord-354e09d6ae53484eb2a249825431a7ee
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

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