Water → 1-Pyrrolidinecarboxylic acid, 2-(1-bromo-8-chloroimidazo(1,5-a)pyrazin-3-yl)-, phenylmethyl ester, (2S)-

HRID 928294Notes

Reaction equation

HRID 928294 reaction equation
[Br:1]N1C(=O)CCC1=O.[Cl:9][C:10]1[C:11]2[N:12]([C:16]([C@@H:19]3[CH2:23][CH2:22][CH2:21][N:20]3[C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])=[N:17][CH:18]=2)[CH:13]=[CH:14][N:15]=1.O.C(OCC)(=O)C>CN(C=O)C.[Cl-].[Na+].O>[Br:1][C:18]1[N:17]=[C:16]([C@@H:19]2[CH2:23][CH2:22][CH2:21][N:20]2[C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[N:12]2[CH:13]=[CH:14][N:15]=[C:10]([Cl:9])[C:11]=12

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 67184N-bromobutanimideHCID 86720301benzyl (2S)-2-{8-chloroimidazo[1,5-a]pyrazin-3-yl}pyrrolidine-1-carboxylate

Product 1

HCID 867203031-Pyrrolidinecarboxylic acid, 2-(1-bromo-8-chloroimidazo(1,5-a)pyrazin-3-yl)-, phenylmethyl ester, (2S)-Yield 83.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

N-Bromosuccinimide (24.69 mmol, 4.4 g) was added to a stirred solution of (S)-benzyl 2-(8-chloroimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate (24.94 mmol, 8.9 g) in DMF (145 mL). The reaction was stirred 3 h at rt. The mixture was poured (slowly) in a stirred mixture of water (145 mL), ethyl acetate (145 mL) and brine (145 mL). The mixture was then transferred into a separating funnel and extracted. The water layer was extracted with 2×145 mL ethyl acetate. The combined organic layers were washed with 3×300 mL water, 300 mL brine, dried over sodium sulfate, filtered and evaporated. The product was purified using silica gel chromatography (ethyl acetate/heptane=3/1 v/v %) to give 8.95 g of (S)-benzyl 2-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate (82.3%).

Workup

  1. additionThe mixture was poured (slowly)
  2. customThe mixture was then transferred into a separating funnel
  3. extractionextracted
  4. extractionThe water layer was extracted with 2×145 mL ethyl acetate
  5. washThe combined organic layers were washed with 3×300 mL water, 300 mL brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe product was purified

Sources & evidence

ORD record
ord-de86550b5cee46648d87cef40e0c81c3
Source dataset
uspto-grants-2016_03
Patent number
US09290504B2

Reaction notes

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