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 897367Notes

Reaction equation

HRID 897367 reaction equation
[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

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-34015fe8a118425c8e0b2f4353fdd2a7
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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