Ammonium Chloride → 1-cyclopentanecarbonyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester

HRID 1895645

Reaction equation

HRID 1895645 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([C:23]([F:26])([F:25])[F:24])=[N:15][C:16]([C:17](=[O:22])N(OC)C)=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:27]1([Mg]Br)[CH2:31][CH2:30][CH2:29][CH2:28]1.[Cl-].[NH4+]>O1CCCC1.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([C:23]([F:25])([F:24])[F:26])=[N:15][C:16]([C:17]([CH:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)=[O:22])=[C:10]2[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 575184541-(methoxy-methyl-carbamoyl)-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl esterHCID 178419650HCID 178419650, compound

Product 1

HCID 575184581-cyclopentanecarbonyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl esterYield 32.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

1-(Methoxy-methyl-carbamoyl)-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester 27e (0.3 g, 0.79 mmol) was dissolved in 20 mL of tetrahydrofuran under stirring, and then cyclopentylmagnesium bromide (0.79 mL, 1.58 mmol) was added dropwise to the solution at 0° C. The reaction mixture was stirred at 0° C. for 3 hours and monitored by thin layer chromatography until the disappearance of the starting materials. 50 mL of saturated ammonium chloride and 10 mL of saturated brine were added. The crude mixture was extracted with ethyl acetate (100 mL×3), and then the combined organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 1-cyclopentanecarbonyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-7-carboxylic acid tert-butyl ester 28a (0.1 g, yield 30%) as a yellow oil.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 3 hours
  2. extractionThe crude mixture was extracted with ethyl acetate (100 mL×3)
  3. dry with materialthe combined organic phase was dried with anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-8576c1afbcf7493db335f3dd819d5180
Source dataset
uspto-grants-2013_08
Patent number
US08513411B2

Linked notes

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