3-Bromoaniline → 6-Amino-4-(3-bromo-phenylamino)-[1,5]naphthyridine-3-carbonitrile

HRID 1266277Notes

Reaction equation

HRID 1266277 reaction equation
C([NH:4][C:5]1[N:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][C:9]([C:15]#[N:16])=[C:8]2Cl)(=O)C.[Br:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=1)[NH2:22].Cl.N1C=CC=CC=1>C(OC(O)C)C>[NH2:4][C:5]1[N:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[CH:10][C:9]([C:15]#[N:16])=[C:8]2[NH:22][C:21]1[CH:23]=[CH:24][CH:25]=[C:19]([Br:18])[CH:20]=1

Participants

5

Reactant 3

HCID 115623-BromoanilineHCID 10176127Pyridinium chlorideHCID 129691036-Acetamido-4-chloro-[1,5]naphthyridine-3-carbonitrile

Product 1

HCID 129691046-Amino-4-(3-bromo-phenylamino)-[1,5]naphthyridine-3-carbonitrileYield 56%

Reagents, catalysts & solvents 1

HCID 101298981-EthoxyethanolSolvent

Procedure

A solution of 6-acetamido-4-chloro-[1,5]naphthyridine-3-carbonitrile (200 mg, 0.81 mmol), 3-bromoaniline (0.5 ml) and pyridine HCl (188 mg) in ethoxyethanol (20 ml) was heated at reflux for 3 hrs. After cooling, the solvent was removed by rotary evaporation, and the residue was cooled and made basic with NH4OH. The aqueous layer was extracted with ethyl acetate. The combined extracts were washed (brine), dried (Na2SO4), and concentrated. The residue was chromatographed (flash column, silica gel, CH2Cl2: ether: MeOH=5:2:0.5) giving the title compound as a yellow solid (229 mg, 56%). mass spectrum (electrospray, m/e): 341.8 (M+H); IR cm-1: 2215, 1628; H-NMR δ (DMSO-d6): 6.816 (2H, bs, NH2), 7.093 (1H, d, C7-H), 7.35-7.43 (3H, m), 7.567 (1H, s), 7.931 (1H, d, C8-H), 8.333 (1H, s, C2-H), 9.236 (1H, s, NH).

Workup

  1. temperatureat reflux for 3 hrs
  2. temperatureAfter cooling
  3. customthe solvent was removed by rotary evaporation
  4. temperaturethe residue was cooled
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washThe combined extracts were washed (brine)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was chromatographed (flash column, silica gel, CH2Cl2: ether: MeOH=5:2:0.5)

Sources & evidence

ORD record
ord-89ed97a4ef44425e9a2849e1909a6237
Source dataset
uspto-grants-2003_04
Patent number
US06548496B2

Reaction notes

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