Water → tert-butyl 1-bromo-3-(trifluoromethyl)-5H,6H,7H,8H-imidazo(1,5-a)pyrazine-7-carboxylate

HRID 920965Notes

Reaction equation

HRID 920965 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[N:7]2[CH2:8][CH2:9][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:11][C:6]2=[CH:5][N:4]=1.[Br:21]N1C(=O)CCC1=O.O>O1CCCC1>[Br:21][C:5]1[N:4]=[C:3]([C:2]([F:1])([F:19])[F:20])[N:7]2[CH2:8][CH2:9][N:10]([C:12]([O:14][C:15]([CH3:17])([CH3:16])[CH3:18])=[O:13])[CH2:11][C:6]=12

Participants

5

Reactant 3

HCID 962WaterHCID 67184N-bromobutanimideHCID 57518450Imidazo[1,5-a]pyrazine-7(8h)-carboxylic acid,5,6-dihydro-3-(trifluoromethyl)-,1,1-dimethylethyl ester

Product 1

HCID 57518451tert-butyl 1-bromo-3-(trifluoromethyl)-5H,6H,7H,8H-imidazo(1,5-a)pyrazine-7-carboxylateYield 108.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tert-butyl 3-(trifluoromethyl)-6,8-dihydro-5H-imidazo[1,5-a]pyrazine-7-carboxylate 11a (370 mg, 1.27 mmol) was dissolved in 30 mL of tetrahydrofuran, followed by addition of N-bromosuccinimide (453 mg, 2.54 mmol) under −78° C. After stirring for 1 hour, the reaction mixture was heated to room temperature and reacted for 12 hours. The reaction mixture was added with 50 mL of H2O, extracted with ethyl acetate (60 mL×3). The organic phase was combined, washed with saturated sodium chloride solution (40 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to obtain crude tert-butyl 1-bromo-3-(trifluoromethyl)-6,8-dihydro-5H-imidazo[1,5-a]pyrazine-7-carboxylate 11b (510 mg) as a light yellow oil. The product was used directly in the next reaction without purification.

Workup

  1. customreacted for 12 hours
  2. extractionextracted with ethyl acetate (60 mL×3)
  3. washwashed with saturated sodium chloride solution (40 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-9b852e0532c54430a847eecf79cfad1e
Source dataset
uspto-grants-2016_03
Patent number
US09273052B2

Reaction notes

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