Methyl 5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylate → 5-(1,1-dioxothiazinan-2-yl)-N-[(4-fluoro-2-methylsulfonyl-phenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

HRID 897367Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 897367
[O:1]=[S:2]1(=[O:23])[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[N:17]=[C:16]([C:18]([O:20]C)=O)[C:15]([OH:22])=[C:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[N:13]2.[Cl-].[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][NH3+:33])=[C:28]([S:34]([CH3:37])(=[O:36])=[O:35])[CH:27]=1>C(O)C>[O:23]=[S:2]1(=[O:1])[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8]1[N:17]=[C:16]([C:18]([NH:33][CH2:32][C:29]2[CH:30]=[CH:31][C:26]([F:25])=[CH:27][C:28]=2[S:34]([CH3:37])(=[O:36])=[O:35])=[O:20])[C:15]([OH:22])=[C:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[N:13]2

Komponenten

4

Edukt 2

HCID 11325194Methyl 5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylateHCID 223464531-[4-fluoro-2-(methylsulfonyl)phenyl]methanaminium Chloride

Produkt 1

HCID 101182515-(1,1-dioxothiazinan-2-yl)-N-[(4-fluoro-2-methylsulfonyl-phenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a slurry of methyl 5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxylate (2.11 g, 6.26 mmol) in ethanol (30 mL) in a pressure flask was added 1-[4-fluoro-2-(methylsulfonyl)phenyl]methanaminium chloride followed by N,N,N-diisopropylethylamine (2.17 mL, 12.52 mmol). The pressure flask was purged with nitrogen and closed. The reaction was heated to 80 degrees C. for 16 hours. The reaction containing residual solids was cooled and determined to be incomplete by LCMS analysis. Added degassed DMF (10 mL) to solubilize the remaining solids, resealed the pressure tube and reheated to 80 degrees C. overnight. The reaction was cooled, transferred to a round bottom flask and reduced to a small volume in vacuo. The residue was partitioned between methylene chloride and saturated aqueous sodium bicarbonate. The organic layer was washed with water, dried over Na2SO4, filtered and reduced to a small volume in vacuo. The residue was crystallized via the addition of 5 mL of methanol. The crystals were filtered and dried in vacuo to afford the title compound.

Aufarbeitung

  1. customThe pressure flask was purged with nitrogen
  2. customclosed
  3. additionThe reaction containing residual solids
  4. temperaturewas cooled
  5. additionAdded
  6. customdegassed DMF (10 mL)
  7. customreheated to 80 degrees C
  8. customovernight
  9. temperatureThe reaction was cooled
  10. customtransferred to a round bottom flask
  11. customThe residue was partitioned between methylene chloride and saturated aqueous sodium bicarbonate
  12. washThe organic layer was washed with water
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. customThe residue was crystallized via the addition of 5 mL of methanol
  16. filtrationThe crystals were filtered
  17. customdried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-34015fe8a118425c8e0b2f4353fdd2a7
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06921759B2

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