Sodium Carbonate → 7-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

HRID 1889064

Reaction equation

HRID 1889064 reaction equation
Br[C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=3[Cl:23])=[O:12])[CH2:10][C:5]2=[N:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:30]1(B(O)O)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>COCCOC.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:23][C:14]1[C:15]([C:19]([F:22])([F:21])[F:20])=[CH:16][CH:17]=[CH:18][C:13]=1[C:11]([N:9]1[CH2:8][CH2:7][N:6]2[C:2]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[N:3][N:4]=[C:5]2[CH2:10]1)=[O:12]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 665992213-Bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Product 1

HCID 665991917-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To 3-bromo-7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine (0.150 g, 0.366 mmol, e.g. see Example 1 for methods of preparation) in 1,2-dimethoxyethane (DME) (3 mL) was added aqueous sodium carbonate solution (1.9 mL, 1 M) followed by phenylboronic acid (0.067 g, 0.549 mmol, commercially available e.g. from Sigma-Aldrich or Strem Chemicals) and dichlorobis(triphenylphosphine)palladium(II) (0.013 g, 0.018 mmol). The reaction mixture was heated at reflux for 7 hours. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (twice). The combined organic fractions were dried, filtered and evaporated. An attempt to purify the crude material on silica gel chromatography using methanol in Dichloromethane (0-20%) as eluent was unsuccessful. The residue was then purified using mass-directed automated (preparative) HPLC (MDAP) to give 7-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine (0.076 g) as a white solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 7 hours
  3. extractionextracted with ethyl acetate (twice)
  4. customThe combined organic fractions were dried
  5. filtrationfiltered
  6. customevaporated
  7. customAn attempt to purify the crude material on silica gel chromatography
  8. customThe residue was then purified

Sources & evidence

ORD record
ord-0839e6c5fe2d4f1aae394e6fab065492
Source dataset
uspto-grants-2013_08
Patent number
US08501946B2

Linked notes

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