Ammonium Chloride → HCID 66734075, compound

HRID 1929716Notes

Reaction equation

HRID 1929716 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH3:18])=[N:15][C:16](I)=[C:10]2[CH:9]1[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[C:23]([F:31])[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.C1(C)C=CC(S([C:46]#[N:47])(=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]([CH3:18])=[N:15][C:16]([C:46]#[N:47])=[C:10]2[CH:9]1[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[C:23]([F:31])[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 87946p-Toluenesulphonyl cyanideHCID 66734224HCID 66734224, compoundHCID 178418339Butyllithium

Product 1

HCID 66734075HCID 66734075, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A cooled (−78° C.) solution of 8-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-1-iodo-3-methyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester (0.666 g; 1.204 mmol) in anhydrous THF (20 ml) was treated dropwise with 1.6M n-BuLi in hexanes (0.76 ml; 1.204 mmol). The resulting reaction mixture was further stirred at −78° C., under nitrogen, for 15 min., and a solution of para-toluenesulfonyl cyanide (0.379 g; 1.987 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, 50/1) afforded 1-cyano-8-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-3-methyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester as a pale yellow solid (0.271 g; 50%). LC-MS: tR=0.96 min.; [M+H]+=453.31 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, 50/1)

Sources & evidence

ORD record
ord-7c245000eb484f2a998f8834b794739e
Source dataset
uspto-grants-2012_05
Patent number
US08188082B2

Reaction notes

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