1,4-Butanesultam → L 870810

HRID 897316Notes

Reaction equation

HRID 897316 reaction equation
[CH2:1]1[CH2:8][NH:7][S:4](=[O:6])(=[O:5])[CH2:3][CH2:2]1.Br[C:10]1[N:19]=[C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[O:21])[C:17]([OH:31])=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2>N1C=CC=CC=1>[O:5]=[S:4]1(=[O:6])[CH2:3][CH2:2][CH2:1][CH2:8][N:7]1[C:10]1[N:19]=[C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[O:21])[C:17]([OH:31])=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

Participants

4

Reactant 2

HCID 3035081,4-ButanesultamHCID 223464015-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide

Product 1

HCID 457930L 870810

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a mixture of 1,4 butanesultam (prepared as in White et al, J. Org Chem. 1987, 52: 2162) (1.00 g, 7.40 mmol), 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (3.06 g, 8.14 mmol), and Cu2O (1.06 g, 7.40 mmol) under an atmosphere of argon was added pyridine (50 mL), and the suspension was stirred at reflux for 16 hr. The reaction was allowed to cool to room temperature and filtered to remove the solids. The solids were washed with chloroform (500 mL). The resulting filtrate was evaporated to dryness and the residue was dissolved in chloroform (1L) and vigorously stirred with a slurry of EDTA (4.0 g) in water (150 mL). After a period of 16 hr, the chloroform extracts were dried (Na2SO4) and evaporated in vacuo. The residue was purified by reverse phase HPLC. (Waters PrePak 500 cartridge C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 75 mL/min over 45 mins). Lyophilization of the pure fractions afforded the title compound as an off-white solid.

Workup

  1. temperatureat reflux for 16 hr
  2. filtrationfiltered
  3. customto remove the solids
  4. washThe solids were washed with chloroform (500 mL)
  5. customThe resulting filtrate was evaporated to dryness
  6. dissolutionthe residue was dissolved in chloroform (1L)
  7. stirringvigorously stirred with a slurry of EDTA (4.0 g) in water (150 mL)
  8. dry with materialthe chloroform extracts were dried (Na2SO4)
  9. customevaporated in vacuo
  10. customThe residue was purified by reverse phase HPLC
  11. wash(Waters PrePak 500 cartridge C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 75 mL/min over 45 mins)

Sources & evidence

ORD record
ord-eb1eca7e6c8b4747aee7ae7083e34651
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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