Benzyloxyamine hydrochloride → 9,10-dihydro-8H-[1,2]oxazino[2',3':1,2]imidazo[4,5-c][1,5]naphthyridine

HRID 415519Notes

Reaction equation

HRID 415519 reaction equation
Cl[CH2:2][CH2:3][CH2:4][C:5]([NH:7][C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:17]=1Cl)=[N:15][CH:14]=[CH:13][CH:12]=2)=O.Cl.C([O:27][NH2:28])C1C=CC=CC=1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C(O)(C)C>[N:15]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:16]=1[C:17]1[N:28]3[O:27][CH2:2][CH2:3][CH2:4][C:5]3=[N:7][C:8]=1[CH:9]=[N:10]2

Participants

5

Reactant 3

HCID 102312Benzyloxyamine hydrochlorideHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 66620109HCID 66620109, compound

Product 1

HCID 666198299,10-dihydro-8H-[1,2]oxazino[2',3':1,2]imidazo[4,5-c][1,5]naphthyridineYield 5.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 4-chloro-N-(4-chloro[1,5]naphthyridin-3-yl)butanamide (3.1 g, 11 mmol) and O-benzylhydroxylamine hydrochloride (2.1 g, 13 mmol) in isopropanol (75 mL) was heated at reflux for 24 hours, then pyridinium p-toluenesulfonate (0.25 g, 1.0 mmol) was added and reflux continued for 48 more hours. The reaction mixture was then concentrated under reduced pressure and dichloromethane (50 mL) and saturated aqueous sodium carbonate (25 mL) were added and the mixture was stirred for 72 hours. The dichloromethane layer was then separated, concentrated under reduced pressure, and the residue purified by chromatography (silica gel eluted with 10% methanol in dichloromethane containing 5 mL of ammonium hydroxide solution per liter) to provide 0.13 g of 9,10-dihydro-8H-[1,2]oxazino[2′,3′:1,2]imidazo[4,5-c][1,5]naphthyridine.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 24 hours
  3. temperaturereflux
  4. concentrationThe reaction mixture was then concentrated under reduced pressure and dichloromethane (50 mL) and saturated aqueous sodium carbonate (25 mL)
  5. additionwere added
  6. customThe dichloromethane layer was then separated
  7. concentrationconcentrated under reduced pressure
  8. customthe residue purified by chromatography (silica gel eluted with 10% methanol in dichloromethane containing 5 mL of ammonium hydroxide solution per liter)

Sources & evidence

ORD record
ord-5b235e9df7744ec3991a5655baa4c94f
Source dataset
uspto-grants-2012_01
Patent number
US08088788B2

Reaction notes

Loading…