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

HRID 1851236Notes

Reaction equation

HRID 1851236 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[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[F:21])[C:11](Cl)=[N:10][C:9]=12)=[O:4].C([O-])([O-])=O.[Na+].[Na+].[CH:29]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)=[O:30]>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[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[F:21])[C:11]([C:34]3[CH:35]=[CH:36][C:31]([CH:29]=[O:30])=[CH:32][CH:33]=3)=[N:10][C:9]=12)=[O:4]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 867030475-Chloro-6-(2,4-difluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid methyl ester

Product 1

HCID 867030506-(2,4-Difluorophenyl)-5-(4-formylphenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid methyl esterYield 44.1%

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

130 mg (0.4 mmol) 5-Chloro-6-(2,4-difluorophenyl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid methyl ester are given in 1.4 mL dimethoxyethane (no complete dissolution). 0.8 mL Na2CO3 solution (10%) and 66 mg (0.44 mmol) 4-formylphenylboronic acid are added. After addition of 15 mg (0.02 mmol) 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) the reaction mixture is purged 3× with argon and heated at 90° C. for 18 hours (complete dissolution). The reaction mixture is cooled down, treated with water and diluted with dichloromethane. The water phase is extracted once more with dichloromethane and the combined organic phases are washed with brine and dried (Na2SO4). The solvent is removed and the crude product purified via chromatography (silicagel, dichloromethane/methanol). 69.4 mg (41.7%) of the desired aldehyde are obtained.

Workup

  1. dissolutionno complete dissolution)
  2. customis purged 3× with argon
  3. dissolution(complete dissolution)
  4. temperatureThe reaction mixture is cooled down
  5. additiontreated with water
  6. additiondiluted with dichloromethane
  7. extractionThe water phase is extracted once more with dichloromethane
  8. washthe combined organic phases are washed with brine
  9. dry with materialdried (Na2SO4)
  10. customThe solvent is removed
  11. customthe crude product purified via chromatography (silicagel, dichloromethane/methanol)

Sources & evidence

ORD record
ord-971397b350fa443595a0095753c0b991
Source dataset
uspto-grants-2015_02
Patent number
US08957064B2

Reaction notes

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