Cesium carbonate → 2-[3-(4-chlorophenyl)-5-oxo-4-(3,3,3-trifluoro-2-hydroxypropyl)-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[2-(trifluoromethyl)benzyl]-acetamide

HRID 660947Notes

Reaction equation

HRID 660947 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11](=[O:13])[N:10]([CH2:14][C:15]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]([F:28])([F:27])[F:26])=[O:16])[N:9]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:35][C:36]([F:41])([F:40])[CH:37]1[O:39][CH2:38]1>CS(C)=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:38][CH:37]([OH:39])[C:36]([F:41])([F:40])[F:35])[C:11](=[O:13])[N:10]([CH2:14][C:15]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]([F:26])([F:27])[F:28])=[O:16])[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 5207692-(Trifluoromethyl)oxirane2×HCID 1361991092-[3-(4-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[2-(tri-fluoromethyl)benzyl]-acetamide

Product 1

HCID 580120652-[3-(4-chlorophenyl)-5-oxo-4-(3,3,3-trifluoro-2-hydroxypropyl)-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[2-(trifluoromethyl)benzyl]-acetamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

100 mg (0.24 mmol) of 2-[3-(4-chlorophenyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[2-(trifluoromethyl)benzyl]-acetamide from Example 243A are placed with 119 mg (0.37 mmol) of caesium carbonate in 0.6 ml of DMSO and treated with 137 mg (1.22 mmol) of 1,1,1-trifluoro-2,3-epoxypropane. This is stirred for 3 hrs at 120° C. Next, 137 mg (1.22 mmol) of 1,1,1-trifluoro-2,3-epoxypropane are again added and the mixture stirred for a further hour at 120° C. The suspension is then cooled to RT, diluted with ethyl acetate and washed three times with saturated ammonium chloride solution. The organic phase is dried over sodium sulphate, filtered and concentrated in vacuo. The crude product is purified by preparative HPLC [Method 10]. 30.6 mg (24% of theory) of the target compound are thus obtained.

Workup

  1. stirringthe mixture stirred for a further hour at 120° C
  2. temperatureThe suspension is then cooled to RT
  3. washwashed three times with saturated ammonium chloride solution
  4. dry with materialThe organic phase is dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product is purified by preparative HPLC [Method 10]
  8. custom30.6 mg (24% of theory) of the target compound are thus obtained

Sources & evidence

ORD record
ord-c9b1ab8451b04776a37e311f6c06eeac
Source dataset
uspto-grants-2011_12
Patent number
US08084481B2

Reaction notes

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