Hydrochloric Acid → HCID 57518479, compound

HRID 1895667Notes

Reaction equation

HRID 1895667 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([C:20]([F:23])([F:22])[F:21])=[N:15][C:16]([C:17]([OH:19])=[O:18])=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24]N(C)CCN(C)C.C([Li])CCC.IC.[Cl-].[NH4+].Cl>C1(C)C=CC=CC=1.O1CCCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([C:20]([F:21])([F:22])[F:23])=[N:15][C:16]([C:17]([OH:19])=[O:18])=[C:10]2[CH:9]1[CH3:24])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 25517Ammonium ChlorideHCID 575184537-[(tert-Butoxy)carbonyl]-3-(trifluoromethyl)-5H,6H,7H,8H-imidazo[1,5-a]pyrazine-1-carboxylic acidHCID 178418339Butyllithium

Product 1

HCID 57518479HCID 57518479, compoundYield 24.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

3-Trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester 27d (0.85 g, 2.54 mmol) was dissolved in a mixture of 25 mL of anhydrous toluene and 8 mL of anhydrous tetrahydrofuran. The reaction flask was placed in a dry ice-acetone bath and cooled to −78° C., and then tetramethyl-ethylenediamine (1.32 mL, 8087 mmol) was added to the flask. n-Butyllithium (5.55 mL, 8.87 mmol) was added dropwise in 5 minutes. After reacting at −78° C. for 15 minutes, iodomethane (0.4 mL, 6.34 mmol) was added dropwise. The reaction mixture was reacted at −78° C. for 10 minutes, then was allowed to warm up to room temperature and reacted for 2 hours until thin lay chromatography showed the starting material disappeared. 15 mL of saturated ammonium chloride and 20 mL of water were added to the reaction mixture successively. The mixture was adjusted to pH 3-4 with 2 N hydrochloric acid, and extracted with ethyl acetate (30 mL×3). The combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 8-methyl-3-trifluoromethyl-5,6-dihydro-8H-imidazo[1,5-a]pyrazine-1,7-dicarboxylic acid 7-tert-butyl ester 39a (0.215 g, yield 24.3%) as a white solid.

Workup

  1. customThe reaction flask was placed in a dry ice-acetone bath
  2. customThe reaction mixture was reacted at −78° C. for 10 minutes
  3. temperatureto warm up to room temperature
  4. customreacted for 2 hours
  5. extractionextracted with ethyl acetate (30 mL×3)
  6. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-189731f1e7d24d7d9c893386febc10ba
Source dataset
uspto-grants-2013_08
Patent number
US08513411B2

Reaction notes

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