Dimethylformamide → Ethyl 8-(benzyloxy)-6-cyano-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate

HRID 494106Notes

Reaction equation

HRID 494106 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:11](Br)[N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:14](=[O:26])[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:52][N:53](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:8][C:9]1[C:10]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[C:11]([C:52]#[N:53])[N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:14](=[O:26])[C:13]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 11776TriphenylphosphineHCID 68864116Ethyl 8-(benzyloxy)-6-bromo-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate

Product 1

HCID 68864512Ethyl 8-(benzyloxy)-6-cyano-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

A solution of ethyl 8-(benzyloxy)-6-bromo-2-(4-fluorobenzyl)-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]-pyrazine-7-carboxylate (1.40 g, 2.79 mmol; Example 1, Step 7), zinc cyanide (0.26 g, 2.23 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.51 g, 0.56 mmol), triphenylphosphine (0.15 g, 0.56 mmol) in DMF (4.5 mL) was purged with nitrogen for 5 minutes. The reaction mixture was heated at 100° C. overnight and concentrated under vacuum. The reaction mixture was partitioned between dichloromethane and brine. The organic extract was dried over sodium sulfate, filtered and concentrated. The residue was subjected to column chromatography on silica gel eluted with 0-10% methanol in chloroform gradient to provide titled product.

Workup

  1. concentrationconcentrated under vacuum
  2. customThe reaction mixture was partitioned between dichloromethane and brine
  3. extractionThe organic extract
  4. dry with materialwas dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. washeluted with 0-10% methanol in chloroform gradient

Sources & evidence

ORD record
ord-fd3ea4ca3a4646e4b1c6b6078d159930
Source dataset
uspto-grants-2009_05
Patent number
US07538112B2

Reaction notes

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