Sodium hydride → 6-Bromo-1-methyl-2,2-dioxo-pyrido[3,2-c]thiazin-4-one

HRID 1478535Notes

Reaction equation

HRID 1478535 reaction equation
[H-].[Na+].[Br:3][C:4]1[N:9]=[C:8]([C:10](OCC)=[O:11])[C:7]([N:15]([CH3:20])[S:16]([CH3:19])(=[O:18])=[O:17])=[CH:6][CH:5]=1>CN(C=O)C>[Br:3][C:4]1[CH:5]=[CH:6][C:7]2[N:15]([CH3:20])[S:16](=[O:18])(=[O:17])[CH2:19][C:10](=[O:11])[C:8]=2[N:9]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 90044112Ethyl 6-bromo-3-[methyl(methylsulfonyl)amino]pyridine-2-carboxylate

Product 1

HCID 900430806-Bromo-1-methyl-2,2-dioxo-pyrido[3,2-c]thiazin-4-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a three necked flask flushed with argon was added NaH (60%, 0.75 g, 18.7 mmol) followed by DMF (10 ml) and stirring was continued for 5 min followed by addition of a solution of ethyl 6-bromo-3-[methyl(methylsulfonyl)amino]pyridine-2-carboxylate (3.16 g, 9.37 mmol) in DMF (35 ml, rinsed with 2×2.5 ml) at ambient temperature giving a reddish solution under effervescence. After stirring for 1 hour the reaction mixture was concentrated under reduced pressure followed by addition of water and ethyl acetate then the phases were separated. The acqueous phase was made slightly acidic using H2SO4 (95-97%) followed by extraction with methylene chloride. The combined organic phases were dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography eluting with ethyl acetate/heptane, gradient, afforded 6-bromo-1-methyl-2,2-dioxo-pyrido[3,2-c]thiazin-4-one as a yellow solid.

Workup

  1. customTo a three necked flask flushed with argon
  2. customgiving a reddish solution under effervescence
  3. stirringAfter stirring for 1 hour the reaction mixture
  4. concentrationwas concentrated under reduced pressure
  5. additionfollowed by addition of water and ethyl acetate
  6. customthe phases were separated
  7. extractionfollowed by extraction with methylene chloride
  8. dry with materialThe combined organic phases were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by flash chromatography
  12. washeluting with ethyl acetate/heptane, gradient

Sources & evidence

ORD record
ord-045a1adc4601465499405fbce72f7ccc
Source dataset
uspto-grants-2016_08
Patent number
US09403845B2

Reaction notes

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