Water → 2-[(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

HRID 714621Notes

Reaction equation

HRID 714621 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH2:14][CH:15]([OH:20])[C:16]([F:19])([F:18])[F:17])[C:10](=[O:13])[NH:11][N:12]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[Br:28][C:29]1[CH:30]=[N:31][CH:32]=[C:33]([CH2:35]Cl)[CH:34]=1.O>CN(C=O)C>[Br:28][C:29]1[CH:34]=[C:33]([CH2:35][N:11]2[C:10](=[O:13])[N:9]([CH2:14][CH:15]([OH:20])[C:16]([F:18])([F:19])[F:17])[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[N:12]2)[CH:32]=[N:31][CH:30]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonate2×HCID 125150693-Bromo-5-(chloromethyl)pyridine hydrochloride2×HCID 584601185-(4-Chlorophenyl)-4-(3,3,3-trifluoro-2-hydroxypropyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

300 mg (0.98 mmol) of the compound from Example 4A and 953 mg (2.93 mmol) of cesium carbonate were dissolved in 4 ml of DMF, and 261 mg (1.10 mmol) of 3-bromo-5-(chloromethyl)-pyridine hydrochloride were added. The mixture was stirred initially at 40° C. for 20 h and then at 70° C. for 24 h. To bring the reaction to completion, a further 130 mg (0.55 mmol) of 3-bromo-5-(chloromethyl)pyridine hydrochloride and 450 mg (1.38 mmol) of cesium carbonate were then added, and the reaction was stirred at 70° C. for another 20 h. After cooling to RT, 10 ml of water were added and the mixture was extracted three times with in each case 10 ml of ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by preparative HPLC [Method 19]. This gave 263 mg (56% of theory) of the target compound.

Workup

  1. waitat 70° C. for 24 h
  2. customthe reaction to completion
  3. stirringthe reaction was stirred at 70° C. for another 20 h
  4. temperatureAfter cooling to RT
  5. extractionthe mixture was extracted three times with in each case 10 ml of ethyl acetate
  6. dry with materialThe combined organic phases were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by preparative HPLC [Method 19]

Sources & evidence

ORD record
ord-b2f756d9380f4ecba3a2dd3f7baa015a
Source dataset
uspto-grants-2015_11
Patent number
US09187466B2

Reaction notes

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