Ammonium Chloride → 1-cyano-3-ethyl-8-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester

HRID 1929715Notes

Reaction equation

HRID 1929715 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH2:18][CH3:19])=[N:15][C:16](I)=[C:10]2[CH:9]1[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[C:24]([F:32])[CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.C1(C)C=CC(S([C:47]#[N:48])(=O)=O)=CC=1.[NH4+].[Cl-]>C1COCC1.CCOCC.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH2:18][CH3:19])=[N:15][C:16]([C:47]#[N:48])=[C:10]2[CH:9]1[CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[C:24]([F:32])[CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 87946p-Toluenesulphonyl cyanideHCID 667341783-ethyl-8-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-1-iodo-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 667338051-cyano-3-ethyl-8-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A cooled (−78° C.) solution of 3-ethyl-8-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-1-iodo-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester (1.040 g; 1.833 mmol) in anhydrous THF (50 ml) was treated dropwise with 1.6M n-BuLi in hexanes (1.6 ml; 2.560 mmol). The resulting reaction mixture was further stirred at −78° C., under nitrogen, for 3 min., and a solution of para-toluenesulfonyl cyanide (0.576 g; 3.025 mmol) in anhydrous THF (5 ml) was then added dropwise. Stirring at −78° C. was continued for 20 min. before aq. sat. NH4Cl (2 ml) was added. The resulting mixture was allowed to warm-up to rt, and water (50 ml), followed by ether (50 ml) were added. The organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH, 25/1) afforded 1-cyano-3-ethyl-8-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester as a pale yellow solid (0.233 g; 27%). LC-MS: tR=1.12 min.; [M+H]+=467.23 g/mol.

Workup

  1. customThe resulting reaction mixture
  2. stirringStirring at −78° C.
  3. additionwas added
  4. temperatureto warm-up to rt
  5. additionwere added
  6. dry with materialThe organic layer was dried over anh. MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure
  9. customPurification by FC (DCM/MeOH, 25/1)

Sources & evidence

ORD record
ord-37558fc25f3e437497dff2dd3da406d4
Source dataset
uspto-grants-2012_05
Patent number
US08188082B2

Reaction notes

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