N-Methoxy-N-methylbenzamide → Imidazo[1,5-a]pyrazine-1,7(8h)-dicarboxylic acid,3-benzoyl-5,6-dihydro-,7-(1,1-dimethylethyl)ester

HRID 1971102Notes

Reaction equation

HRID 1971102 reaction equation
Br[C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:5]2=[C:4]([C:18]([OH:20])=[O:19])[N:3]=1.CON(C)[C:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([Li])(C)(C)C>C1COCC1>[C:24]([C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:5]2=[C:4]([C:18]([OH:20])=[O:19])[N:3]=1)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 569575N-Methoxy-N-methylbenzamideHCID 576354283-bromo-7-[(tert-butoxy)carbonyl]-5H,6H,7H,8H-imidazo[1,5-a]pyrazine-1-carboxylic acidHCID 178418306HCID 178418306, compound

Product 1

HCID 57635676Imidazo[1,5-a]pyrazine-1,7(8h)-dicarboxylic acid,3-benzoyl-5,6-dihydro-,7-(1,1-dimethylethyl)esterYield 45.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Under a nitrogen atmosphere Compound 11 (0.15 g, 0.43 mmol) was dissolved in THF (2 mL) and N-methoxy-N-methylbenzamide (0.14 g, 0.86 mmol) was added. The resulting solution was cooled to −78° C. and tert-Butyl lithium (1.7M in THF, 1.02 mL, 1.73 mmol) was added dropwise. The resulting mixture was stirred and cooled for 1 h and quenched with NH4Cl saturated solution. The solid was removed by filtration and the filtrate was concentrated, acidified to pH 6 with 5% TFA and extracted with 20% i-PrOH/DCM. The organic layer was concentrated, diluted with DCM, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give product 25A (0.072 g, 45%). LCMS (+ESI) m/z 372.1 [M+H]+.

Workup

  1. temperaturecooled for 1 h
  2. customquenched with NH4Cl saturated solution
  3. customThe solid was removed by filtration
  4. concentrationthe filtrate was concentrated
  5. extractionextracted with 20% i-PrOH/DCM
  6. concentrationThe organic layer was concentrated
  7. additiondiluted with DCM
  8. washwashed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c5966133e04e4ee1972ea0b25e040b28
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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