1H-1,2,4-Triazole → 7-N-(tert-Butoxycarbonyl)-8-([1,2,4]triazol-4-ylmethyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

HRID 133079Notes

Reaction equation

HRID 133079 reaction equation
[NH:1]1[CH:5]=[N:4][CH:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]2[N:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[N:27]=[C:21]2[CH:20]1[CH2:32]OS(C)(=O)=O)=[O:18])([CH3:15])([CH3:14])[CH3:13]>CN(C=O)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]2[N:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[N:27]=[C:21]2[CH:20]1[CH2:32][N:4]1[CH:3]=[N:2][N:1]=[CH:5]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 92571H-1,2,4-TriazoleHCID 11430Potassium CarbonateHCID 877981657-N-(tert-Butoxycarbonyl)-8-(methanesulfonyloxymethyl)-2-(trifluoromethyl) 5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

Product 1

HCID 693628917-N-(tert-Butoxycarbonyl)-8-([1,2,4]triazol-4-ylmethyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazineYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 47 mg (0.683 mmol) of [1,2,4]triazole in 1.0 mL of DMF was added 189 mg (1.365 mmol) of potassium carbonate. The mixture was heated at 50° C. for 15 min. To this was added 182 mg (0.455 mmol) of 7-N-(tert-butoxycarbonyl)-8-(methanesulfonyloxymethyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine. The mixture was stirred at 50° C. for 14 h. DMF was removed in vacuo and the residue was partitioned between ethyl acetate and water. The aqueous phase was extracted with three portions of ethyl acetate. The combined organics were dried over magnesium sulfate and concentrated to give 107 mg of an orange oil. The mixture was eluted on a preparative TLC plate (silica gel, 50% ethyl acetate/hexane). The plate was scraped and the product eluted from the silica gel with 80:15:1 chloroform/methanol/ammonium hydroxide to give the title compound.

Workup

  1. customDMF was removed in vacuo
  2. customthe residue was partitioned between ethyl acetate and water
  3. extractionThe aqueous phase was extracted with three portions of ethyl acetate
  4. dry with materialThe combined organics were dried over magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a23d649a3f17462bb850be2df7935785
Source dataset
uspto-grants-2008_06
Patent number
US07390809B2

Reaction notes

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