Diethyl Oxalate → 4-[(1,1-dioxido-1,2-thiazinan-2-yl)methyl]-2-(4-fluorobenzyl)-8,9-dihydroxy-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione

HRID 2109849Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2109849
[C:1]([N:4]1[CH:9]([CH2:10][N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][S:12]2(=[O:18])=[O:17])[CH2:8][N:7]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[C:6](=[O:27])[CH2:5]1)(=[O:3])[CH3:2].[C:28](OCC)(=[O:34])[C:29](OCC)=[O:30].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1>CN(C=O)C>[O:17]=[S:12]1(=[O:18])[CH2:13][CH2:14][CH2:15][CH2:16][N:11]1[CH2:10][CH:9]1[N:4]2[C:1](=[O:3])[CH:2]=[C:28]([OH:34])[C:29]([OH:30])=[C:5]2[C:6](=[O:27])[N:7]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[CH2:8]1

Komponenten

6

Edukt 4

HCID 7268Diethyl OxalateHCID 8028Tetrahydrofuran2×HCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 576346514-Acetyl-5-[(1,1-Dioxido-1,2-thiazinan-2-yl)methyl]-1-(4-fluorobenzyl)-piperazin-2-one

Produkt 1

HCID 547052744-[(1,1-dioxido-1,2-thiazinan-2-yl)methyl]-2-(4-fluorobenzyl)-8,9-dihydroxy-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a cold (0° C.) solution of 4-acetyl-5-[(1,1-dioxido-1,2-thiazinan-2-yl)methyl]-1-(4-fluorobenzyl)-piperazin-2-one (75 mg, 0.19 mmol) and diethyl oxalate (29 μL, 0.21 mmol) in DMF (3 mL) under an atmosphere of nitrogen, a solution of sodium bis(trimethylsilyl)amide in THF (1M, 0.21 mL, 0.21 mmol) was added over a period of 0.5 h and stirred at the temperature for 30 min. Then additional sodium bis(trimethylsilyl)amide in THF (1M, 0.21 mL, 0.21 mmol) was added over a period of 0.5 h and stirred at the temperature for 1 h. The product mixture was concentrated under vacuum, and the residue partitioned between aqueous HCl and ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to HPLC purification on C-18 stationary phase eluted with water/acetonitrile/TFA mobile phase. Collection and lyophilization of appropriate fractions provided the title compound.

Aufarbeitung

  1. stirringstirred at the temperature for 1 h
  2. concentrationThe product mixture was concentrated under vacuum
  3. customthe residue partitioned between aqueous HCl and ethyl acetate
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was subjected to HPLC purification on C-18 stationary phase
  9. washeluted with water/acetonitrile/TFA mobile phase
  10. customCollection and lyophilization of appropriate fractions

Quellen und Nachweise

ORD-Eintrag
ord-fb74c6886a72467d887c50102143032b
Quelldatensatz
uspto-grants-2009_04
Patentnummer
US07517532B2

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