Tetrahydrofuran → HCID 69316492, compound

HRID 2114837Notes

Reaction equation

HRID 2114837 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:28]([NH:30][CH3:31])=[O:29])=[C:11]([Br:27])[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.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.Br[CH2:48][CH:49]=[C:50]([CH3:52])[CH3:51]>CN(C=O)C>[CH3:51][C:50]([CH3:52])=[CH:49][CH2:48][N:30]([CH3:31])[C:28]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[C:13]2[C:14](=[O:26])[N:15]([CH2:18][C:19]3[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=3)[CH2:16][CH2:17][N:12]2[C:11]=1[Br:27])=[O:29]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 700922-Butene, 1-bromo-3-methyl-HCID 2733832Lithium HexamethyldisilazideHCID 58857941HCID 58857941, compound

Product 1

HCID 69316492HCID 69316492, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a cold (0° C.) solution of 8-(benzyloxy)-6-bromo-2-(4-fluorobenzyl)-N-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo-[1,2-a]pyrazine-7-carboxamide (0.24 g, 0.50 mmol) in anhydrous DMF (10 mL) under an atmosphere of nitrogen, a solution of lithium bis(trimethylsilyl)amide in THF (1 M, 0.55 mmol) was added. The reaction mixture was stirred at 0° C. for 15 minutes and treated with 4-bromo-2-methyl-2-butene (0.15 mL, 1.5 mmol; passed through activated basic alumina). The reaction mixture was stirred at rt for 40 minutes and concentrated under vacuum. The residue was partitioned between methylene chloride and dilute aqueous HCl. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with ethyl acetate. Collection and concentration of appropriate fractions provided the titled product. ES MS M+1=486,488 (1:1)

Workup

  1. stirringThe reaction mixture was stirred at rt for 40 minutes
  2. concentrationconcentrated under vacuum
  3. customThe residue was partitioned between methylene chloride and dilute aqueous HCl
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. washeluted with ethyl acetate
  10. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-5cf4ab47c60b45f8a4a09cb0fde64baa
Source dataset
uspto-grants-2008_10
Patent number
US07435735B2

Reaction notes

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