2-Bromo-N,N-dimethylacetamide → 7-N-(tert-Butoxycarbonyl)-8-[2-(dimethylamino)-2-oxoethyl]-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

HRID 133080Notes

Reaction equation

HRID 133080 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:16]=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].Br[CH2:30][C:31]([N:33]([CH3:35])[CH3:34])=[O:32]>O1CCCC1.CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[N:14]=[C:15]([C:17]([F:18])([F:19])[F:20])[N:16]=[C:10]2[CH:9]1[CH2:30][C:31]([N:33]([CH3:35])[CH3:34])=[O:32])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 2255442-Bromo-N,N-dimethylacetamideHCID 2724682Lithium diisopropylamideHCID 53393358tert-Butyl 2-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazine-7(8H)-carboxylate

Product 1

HCID 693632797-N-(tert-Butoxycarbonyl)-8-[2-(dimethylamino)-2-oxoethyl]-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-alpha]pyrazine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 2.13 g (7.30 mmol) of 7-N-(tert-butoxycarbonyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-α]pyrazine (Example 2, Step A) in 10 mL of tetrahydrofuran at −78° C. was added lithium diisopropylamide (4.02 mL of a 2.0M solution in heptane/tetrahydrofuran/ethylbenzene, 8.03 mmol). The mixture was allowed to stir at −78° C. for 15 min, and then 2-bromo-N,N-dimethylacetamide from Step A in 5 mL of tetrahydrofuran was added, and the mixture slowly warmed to ambient temperature over 18 h. The reaction was quenched with aqueous ammonium chloride and the aqueous layer was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated. Purification by flash chromatography (silica gel, gradient of 50% to 75% ethyl acetate/hexane) yielded the title compound. LC/MS 322 ((M+1)-t-butyl).

Workup

  1. temperaturethe mixture slowly warmed to ambient temperature over 18 h
  2. customThe reaction was quenched with aqueous ammonium chloride
  3. extractionthe aqueous layer was extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customPurification by flash chromatography (silica gel, gradient of 50% to 75% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-afcf7d6503a34e199fae461b24d58255
Source dataset
uspto-grants-2008_06
Patent number
US07390809B2

Reaction notes

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