Sodium Carbonate → 5-(4-Chlorophenyl)-4-(3,3,3-trifluoro-2-hydroxypropyl)-2-({5-[2-(trifluoromethyl)phenyl]pyridin-3-yl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 714698Notes

Reaction equation

HRID 714698 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13](=[O:14])[N:12]([CH2:15][CH:16]([OH:21])[C:17]([F:20])([F:19])[F:18])[C:11]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)=[N:10]2)[CH:5]=[N:6][CH:7]=1.[F:29][C:30]([F:41])([F:40])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[Cl:28][C:25]1[CH:26]=[CH:27][C:22]([C:11]2[N:12]([CH2:15][CH:16]([OH:21])[C:17]([F:20])([F:19])[F:18])[C:13](=[O:14])[N:9]([CH2:8][C:4]3[CH:5]=[N:6][CH:7]=[C:2]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[C:30]([F:41])([F:40])[F:29])[CH:3]=3)[N:10]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 674086672-[(5-Bromopyridin-3-yl)methyl]-5-(4-chlorophenyl)-4-(3,3,3-trifluoro-2-hydroxypropyl)-2,4-di-hydro-3H-1,2,4-triazol-3-one

Product 1

HCID 866909255-(4-Chlorophenyl)-4-(3,3,3-trifluoro-2-hydroxypropyl)-2-({5-[2-(trifluoromethyl)phenyl]pyridin-3-yl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

72 mg (0.15 mmol) of the compound from Example 28A and 43 mg (0.23 mmol) of 2-(trifluoro-methyl)phenylboronic acid were dissolved in 2 ml of dioxane. For 10 min, a stream of argon was passed through this solution, and 8.7 mg (0.008 mmol) of tetrakis(triphenylphosphine)palladium(0) were then added under argon. The mixture was heated to the boil, and 0.15 ml (0.30 mmol) of a 2 N aqueous sodium carbonate solution was added under argon. The mixture was stirred under reflux for 20 h. After cooling to RT, the mixture was diluted with 10 ml of water and extracted twice with in each case 15 ml of ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified chromatographically [Method 19]. This gave 36 mg (44% of theory) of the target compound.

Workup

  1. additionwere then added under argon
  2. additionwas added under argon
  3. temperatureunder reflux for 20 h
  4. extractionextracted twice with in each case 15 ml of ethyl acetate
  5. dry with materialThe combined organic phases were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified chromatographically [Method 19]

Sources & evidence

ORD record
ord-89b5691faad24541b9a3741f4df8bfd1
Source dataset
uspto-grants-2015_11
Patent number
US09187466B2

Reaction notes

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