5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide → HCID 22346299, compound

HRID 897310Notes

Reaction equation

HRID 897310 reaction equation
Br[C:2]1[N:11]=[C:10]([C:12]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[O:13])[C:9]([OH:23])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[CH3:24][N:25]([CH3:34])[C:26](=[O:33])[CH2:27][NH:28][S:29]([CH3:32])(=[O:31])=[O:30]>N1C=CC=CC=1.[Cu-]=O>[F:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][NH:14][C:12]([C:10]2[C:9]([OH:23])=[C:8]3[C:3]([CH:4]=[CH:5][CH:6]=[N:7]3)=[C:2]([N:28]([CH2:27][C:26]([N:25]([CH3:34])[CH3:24])=[O:33])[S:29]([CH3:32])(=[O:31])=[O:30])[N:11]=2)=[O:13])=[CH:17][CH:18]=1

Participants

5

Reactant 2

HCID 223464015-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamideHCID 22346487HCID 22346487, compound

Product 1

HCID 22346299HCID 22346299, compound

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 1049PyridineSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-[1,6]naphthyridine-7-carboxamide (0.57 g, 1.5 mmol), N,N-dimethyl-2-[(methylsulfonyl)amino]acetamide from Step 1 (0.25 g, 1.38 mmol) and copper (I) oxide (0.10 g, 0.70 mmol) in pyridine (5 mL) was heated in an oil bath at 115° C. overnight. The resultant mixture was concentrated under vacuum. To the residue, chloroform (200 mL) and a saturated aqueous solution of ethylenediamine tetraacetic acid, disodium salt (75 mL) was added. The mixture was stirred vigorously at room temp for 2 hours in the presence of air, and filtered through a pad of Celite. The organic extract was separated, dried over anhydrous magnesium sulfate, filtered and concentrated under vacuum. The residue was dissolved in DMSO and 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 as white solid.

Workup

  1. concentrationThe resultant mixture was concentrated under vacuum
  2. additionTo the residue, chloroform (200 mL) and a saturated aqueous solution of ethylenediamine tetraacetic acid, disodium salt (75 mL) was added
  3. filtrationfiltered through a pad of Celite
  4. extractionThe organic extract
  5. customwas separated
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. dissolutionThe residue was dissolved in DMSO
  10. customsubjected to HPLC purification on C-18 stationary phase
  11. washeluted with water/acetonitrile/TFA mobile phase
  12. customCollection and lyophilization of appropriate fractions

Sources & evidence

ORD record
ord-b09d4aa033f64e31bb8d028a17f4259b
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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