Diisopropylethylamine → (S)-tert-butyl 1-(1-methoxy-3,3-dimethyl-1-oxobutan-2-ylcarbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate

HRID 535937Notes

Reaction equation

HRID 535937 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:15][C:16]([C:17]([OH:19])=O)=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:26][C@@H:27]([C:32]([CH3:35])([CH3:34])[CH3:33])[C:28]([O:30][CH3:31])=[O:29].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.O>[CH3:31][O:30][C:28](=[O:29])[C@@H:27]([NH:26][C:17]([C:16]1[N:15]=[C:14]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][C:10]=12)=[O:19])[C:32]([CH3:35])([CH3:34])[CH3:33]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11309583Methyl L-tert-leucinateHCID 576351557-(Tert-butoxycarbonyl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxylic acid2×

Product 1

HCID 57635284(S)-tert-butyl 1-(1-methoxy-3,3-dimethyl-1-oxobutan-2-ylcarbamoyl)-3-phenyl-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylateYield 99.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 7-(tert-butoxycarbonyl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxylic acid (Intermediate 3B) (2.0 g, 5.82 mmol) in DMF was added (S)-methyl 2-amino-3,3-dimethylbutanoate (1.18 g, 8.15 mmol), followed by DIEA (2.26 g, 17.47 mmol). The resulting mixture was stirred for 20 min and TBTU (2.43 g, 7.57 mmol) was added and the mixture was stirred overnight. The reaction mixture was diluted with water and extracted with EtOAc, washed with water, brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography eluting with ethyl acetate/hexanes 10-50% gradient to give Intermediate 22A 2.73 g (98%). LCMS (+ESI) m/z 470.0 [M+H]+.

Workup

  1. stirringthe mixture was stirred overnight
  2. extractionextracted with EtOAc
  3. washwashed with water, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography
  8. washeluting with ethyl acetate/hexanes 10-50% gradient

Sources & evidence

ORD record
ord-37cad992d3534ba0bf99e958c8877741
Source dataset
uspto-grants-2014_10
Patent number
US08859538B2

Reaction notes

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