Acrylonitrile → Methyl 4-(3-(4-cyano-1-methoxy-1-oxobutan-2-yl)-8-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]pyrazin-1-yl)benzoate

HRID 62456Notes

Reaction equation

HRID 62456 reaction equation
[CH3:1][O:2][C:3]1[CH:34]=[C:33]([O:35][CH3:36])[CH:32]=[CH:31][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[N:9]([C:13]([CH2:26][C:27]([O:29][CH3:30])=[O:28])=[N:14][C:15]=2[C:16]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][CH:17]=2)[CH:10]=[CH:11][N:12]=1.[C:37](#[N:40])[CH:38]=[CH2:39].CC([O-])(C)C.[K+].CCOC(C)=O>C1COCC1.C(Cl)Cl>[C:37]([CH2:38][CH2:39][CH:26]([C:13]1[N:9]2[CH:10]=[CH:11][N:12]=[C:7]([NH:6][CH2:5][C:4]3[CH:31]=[CH:32][C:33]([O:35][CH3:36])=[CH:34][C:3]=3[O:2][CH3:1])[C:8]2=[C:15]([C:16]2[CH:17]=[CH:18][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:24][CH:25]=2)[N:14]=1)[C:27]([O:29][CH3:30])=[O:28])#[N:40]

Participants

7

Reactant 4

HCID 7855AcrylonitrileHCID 8857Ethyl Acetate2×HCID 23665647Potassium tert-butoxideHCID 90304136Methyl 4-(8-((2,4-dimethoxybenzyl)amino)-3-(2-methoxy-2-oxoethyl)imidazo[1,5-a]pyrazin-1-yl)benzoate

Product 1

HCID 90304033Methyl 4-(3-(4-cyano-1-methoxy-1-oxobutan-2-yl)-8-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]pyrazin-1-yl)benzoateYield 94.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-(8-((2,4-dimethoxybenzyl)amino)-3-(2-methoxy-2-oxoethyl) imidazo[1,5-a]pyrazin-1-yl)benzoate (11.4 g, 23.3 mmol) in THF (100 mL) was added acrylonitrile (1.4 g, 25.6 mmol) and t-BuOK (2.3 mL, 1M in THF). The mixture was stirred at RT for 2 hrs. The reaction was complete detected by TLC (PE/EtOAc 1:1). The mixture was extracted with EA and water, the organic layer was dried and concentrated, the residue was purified by column chromatography on silica gel eluted with PE:EA:DCM=2:1:1 to give methyl 4-(3-(4-cyano-1-methoxy-1-oxobutan-2-yl)-8-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]pyrazin-1-yl)benzoate (12 g, yield 94%).

Workup

  1. extractionThe mixture was extracted with EA and water
  2. customthe organic layer was dried
  3. concentrationconcentrated
  4. customthe residue was purified by column chromatography on silica gel
  5. washeluted with PE

Sources & evidence

ORD record
ord-c566c6bf11e34b46b98eeec272d381f1
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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