Methyl 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylate → Methyl 5-(1,1-dioxido-5-methyl-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy[1,6]-naphthyridine-7-carboxylate

HRID 897338Notes

Reaction equation

HRID 897338 reaction equation
Br[C:2]1[N:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[C:9]([OH:16])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[CH3:17][N:18]1[CH2:24][CH2:23][S:22](=[O:26])(=[O:25])[NH:21][CH2:20][C:19]1=[O:27]>N1C=CC=CC=1.[Cu-]=O>[O:26]=[S:22]1(=[O:25])[CH2:23][CH2:24][N:18]([CH3:17])[C:19](=[O:27])[CH2:20][N:21]1[C:2]1[N:11]=[C:10]([C:12]([O:14][CH3:15])=[O:13])[C:9]([OH:16])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2

Participants

5

Reactant 2

HCID 22343006Methyl 5-bromo-8-hydroxy-1,6-naphthyridine-7-carboxylateHCID 223463175-Methyl-1,2,5-thiadiazepan-4-one 1,1-dioxide

Product 1

HCID 22346441Methyl 5-(1,1-dioxido-5-methyl-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy[1,6]-naphthyridine-7-carboxylate

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 1049PyridineSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of methyl 5-bromo-8-hydroxy[1,6]naphthyridine-7-carboxylate (0.28 g, 1.0 mmol), 5-methyl-1,2,5-thiadiazepan-4-one 1,1-dioxide from step 2 (0.178 g, 1.0 mmol) and copper (I) oxide (0.143 g, 1.0 mmol) in pyridine (5 mL) was heated in an oil bath at 115° C. overnight. The resultant mixture was filtered, and the filtrate concentrated under vacuum. The residue was treated with a mixture of chloroform (50 mL) and ethylenediamine tetraacetic acid, disodium salt (5 g) in water (30 mL) and stirred vigorously at room temp in the presence of air for 5 hours. The slurry was filtered through a pad of Celite. The organic extract was separated, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was triturated with methanol (25 mL) and the resultant suspension stirred at room temperature overnight. The solid was filtered, washed with cold (0° C.) methanol, and dried under vacuum to provide methyl 5-(1,1-dioxido-5-methyl-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy[1,6]-naphthyridine-7-carboxylate as light brown solid.

Workup

  1. filtrationThe resultant mixture was filtered
  2. concentrationthe filtrate concentrated under vacuum
  3. additionThe residue was treated with a mixture of chloroform (50 mL) and ethylenediamine tetraacetic acid, disodium salt (5 g) in water (30 mL)
  4. filtrationThe slurry was filtered through a pad of Celite
  5. extractionThe organic extract
  6. customwas separated
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was triturated with methanol (25 mL)
  11. stirringthe resultant suspension stirred at room temperature overnight
  12. filtrationThe solid was filtered
  13. washwashed with cold (0° C.) methanol
  14. customdried under vacuum

Sources & evidence

ORD record
ord-1b719b32ae9f471196c0c9620cc69403
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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