Nitrogen → 3-[3-([1,2,4]Triazol-4-yl)phenyl]-7-trifluoromethylimidazo[1,2-a]pyrimidine

HRID 478258Notes

Reaction equation

HRID 478258 reaction equation
Br[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]([F:14])([F:13])[F:12])=[N:10][C:5]2=[N:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[N:23]#[N:24].CCO[C:28]([CH3:30])=O>CC(N(C)C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:23]1[N:24]=[CH:5][N:6]([C:7]2[CH:8]=[C:9]([C:2]3[N:6]4[CH:7]=[CH:8][C:9]([C:11]([F:14])([F:13])[F:12])=[N:10][C:5]4=[N:4][CH:3]=3)[CH:11]=[CH:28][CH:30]=2)[CH:2]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 113914623-Bromo-7-(trifluoromethyl)imidazo[1,2-a]pyrimidine

Product 1

HCID 99235563-[3-([1,2,4]Triazol-4-yl)phenyl]-7-trifluoromethylimidazo[1,2-a]pyrimidineYield 40%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 3-bromo-7-trifluoromethylimidazo[1,2-a]pyrimidine (139 mg, 0.53 mmol), the foregoing boronate ester (269 mg, 1.05 mmol) and K3PO4 (483 mg, 2.1 mmol) in DMA (3 ml) was degassed with a stream of N2 for 5 min and then tetrakis(triphenylphosphine)palladium(0) (60 mg, 10 mol %) was added and the reaction heated at 65° C. for 70 min. EtOAc (100 ml) was added and the mixture washed with H2O (3×100 ml) and brine (100 ml), dried (MgSO4) and concentrated under reduced pressure while dry loading onto silica. The residue was purified by column chromatography on silica using 5% MeOH in dichloromethane to yield 3-[3-([1,2,4]triazol-4-yl)phenyl]-7-trifluoromethylimidazo[1,2-a]pyrimidine (70 mg, 40%), which was then recrystallised from EtOAc/isohexanes: δH (400 MHz, d6-DMSO) 7.55 (1H, d, J 7.2), 7.70-7.90 (3H, m), 8.16 (1H, s), 8.39 (1H, s), 9.24 (2H, s), 9.48 (1H, d, J 7.2); m/z (ES+) 331 (M+H+).

Workup

  1. washthe mixture washed with H2O (3×100 ml) and brine (100 ml)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customwhile dry loading onto silica
  5. customThe residue was purified by column chromatography on silica using 5% MeOH in dichloromethane

Sources & evidence

ORD record
ord-0aed42ea4adb4f368582c3b552297ef8
Source dataset
uspto-grants-2003_11
Patent number
US06642229B2

Reaction notes

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