Sodium Carbonate → 6-(2,6-Difluorophenyl)-5-(4-formylphenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid methyl ester

HRID 1851234Notes

Reaction equation

HRID 1851234 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][N:8]2[CH:13]=[C:12]([C:14]3[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=3[F:21])[C:11](Cl)=[N:10][C:9]=12)=[O:4].[C:23]([O-:26])([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]>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][N:8]2[CH:13]=[C:12]([C:14]3[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=3[F:21])[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH:23]=[O:26])=[CH:16][CH:15]=3)=[N:10][C:9]=12)=[O:4]

Participants

5

Reactant 2

HCID 10340Sodium CarbonateHCID 867030445-Chloro-6-(2,6-difluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid methyl ester

Product 1

HCID 867030466-(2,6-Difluorophenyl)-5-(4-formylphenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid methyl ester

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

2.3 g (7.1 mmol) 5-Chloro-6-(2,6-difluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid methyl ester are given in 24 mL dimethoxyethane. 13.9 mL Na2CO3 solution (10%) and 1.18 g (7.8 mmol) 4-formylboronic acid are added. After addition of 0.26 g (0.32 mmol) 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) the reaction mixture is purged 3× with argon and heated at 90° C. for 2 hours. The reaction mixture is cooled down, treated with water and extracted 3 times with dichloromethane. The organic phase is washed with brine and dried (Na2SO4). The solvent is removed and the crude product purified via chromatography (silicagel, dichloromethane/methanol). 2.57 g (64.4%) of the slightly contaminated compound are obtained.

Workup

  1. customis purged 3× with argon
  2. temperatureThe reaction mixture is cooled down
  3. additiontreated with water
  4. extractionextracted 3 times with dichloromethane
  5. washThe organic phase is washed with brine
  6. dry with materialdried (Na2SO4)
  7. customThe solvent is removed
  8. customthe crude product purified via chromatography (silicagel, dichloromethane/methanol)
  9. custom2.57 g (64.4%) of the slightly contaminated compound are obtained

Sources & evidence

ORD record
ord-55965f5b0f45427fbd7dc31e38dcdca5
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

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