Water → HCID 86640827, compound

HRID 1929713Notes

Reaction equation

HRID 1929713 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])=[CH:24][CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN([CH:35]=[O:36])C.O.CC(=O)OCC>C1COCC1>[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]([CH:35]=[O:36])=[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])=[CH:24][CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 66734220HCID 66734220, compound

Product 1

HCID 86640827HCID 86640827, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A cooled (−30° C.) solution of 3-ethyl-1-iodo-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester (1.000 g; 1.820 mmol) in anhydrous THF (10 ml) was treated dropwise with 1-Methylmagnesium bromide in THF (4.0 ml; 4.0 mmol), and the resulting suspension was then allowed to warm-up to rt in 10 min. After cooling to −35° C., a mixture of anhydrous DMF (2.0 ml; 25.831 mmol) and anhydrous THF (2 ml) was added dropwise, and the resulting mixture was then allowed to warm-up to rt (in 30 min.), and was further stirred at rt for 16 h. Water (2 ml) and EA were then successively added, and this mixture was washed with aq. sat. NH4Cl. The organic extract was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure (yellow oil; 950 mg). Purification by FC (EA/heptane=1/9 to 1/1) gave the pure product 3-ethyl-1-formyl-8-[2-(4-trifluoromethyl-phenyl)-ethyl]-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester as a colorless oil (640 mg; 78%). LC-MS: tR=1.01 min.; [M+H]+=452.12 g/mol.

Workup

  1. temperatureAfter cooling to −35° C.
  2. additionwas added dropwise
  3. temperatureto warm-up to rt (in 30 min.)
  4. washthis mixture was washed with aq. sat. NH4Cl
  5. extractionThe organic extract
  6. dry with materialwas dried over anh. MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure (yellow oil; 950 mg)
  9. customPurification by FC (EA/heptane=1/9 to 1/1)

Sources & evidence

ORD record
ord-2f1ef673d8934dcf9a78168b60b87eb0
Source dataset
uspto-grants-2012_05
Patent number
US08188082B2

Reaction notes

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