Reaction #607452

Reaction equation

Xanthine Adenosine

3-Nitro-4-hydroxyquinoline

3-nitro-4-hydroxyquinoline

phosphorus oxychloride

→

Compound 6

3-nitro-4-chloroquinoline

Conditions

Workup

1. 1
   TemperatureThe mixture was refluxed for 30 minutes
2. 2
   TemperatureAfter cooling the solvent
3. 3
   workup.ADDITIONwas poured
4. 4
   Otherover crushed ice
5. 5
   workup.STIRRINGwhile stirring
6. 6
   OtherAfter 1 hour the solid that was formed
7. 7
   Filtrationwas filtered off
8. 8
   Washwashed with cold water
9. 9
   workup.DISSOLUTIONdissolved in ethyl acetate
10. 10
    ExtractionThe solution was extracted with ice-cold NaOH (1 M) till pH=8-9
11. 11
    Dryingdried over MgSO4
12. 12
    OtherThe solvent was evaporated
13. 13
    Otherthe residue was dried

Procedure

Compound 6 was prepared as described elsewhere [Van Galen, P. J. M. et. al. 1-H-imidazo[4,5-c]quinolin-4-amines: Novel Non-Xanthine Adenosine Antagonists. J. Med. Chem. 1991, 34, 1202-1206]. In brief, 3-Nitro-4-hydroxyquinoline 5 (5.7 g, 30 mmol) was added to phosphorus oxychloride (70.0 g, 41.2 ml, 450 mmol) with stirring. The mixture was refluxed for 30 minutes. After cooling the solvent was poured over crushed ice while stirring. After 1 hour the solid that was formed was filtered off, washed with cold water and dissolved in ethyl acetate. The solution was extracted with ice-cold NaOH (1 M) till pH=8-9 and dried over MgSO4. The solvent was evaporated and the residue was dried. Yield: 5.05 g (81%). Mp.: 118°-119° C. 1H NMR (DMSO-d6): δ 7.94-8.11 (m, 2H, Ar); 8.25 (d, 1H, J=8.0 Hz, Ar); 8.47 (d, 1H, J=9.5 Hz, Ar); 9.42 (s, 1H, Ar).

Source