Reacción #532627

Ecuación de reacción

NH4SCN

4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenylamine

NH4SCN

Br2

Br2

→

6-(6,7-dimethoxy-quinolin-4-yloxy)-5-fluoro-benzothiazol-2-ylamine

Rendimiento 48.1%

Disolventes

AcOH

AcOH

AcOH

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturathe mixture cooled in an ice bath
2. 2
   workup.ADDITIONAfter addition
3. 3
   workup.STIRRINGthe reaction mixture was stirred at room temperature
4. 4
   workup.STIRRINGdropwise with stirring
5. 5
   TemperaturaThe reaction mixture was then heated
6. 6
   Temperaturato reflux for several minutes
7. 7
   Filtraciónsolids were filtered
8. 8
   Lavadowashed with AcOH
9. 9
   FiltraciónThe resulting solids were filtered
10. 10
    Lavadowashed with H2O
11. 11
    Otrodried under high vacuum

Procedimiento

4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenylamine (1.00 g, 3.18 mmol) was dissolved in AcOH (8.0 ml), to which was added NH4SCN (486 mg, 6.38 mmol) and the mixture cooled in an ice bath. Br2 (0.33 ml, 6.42 mmol) in AcOH (0.33 ml) was added dropwise with stirring. After addition was complete, the reaction mixture was stirred at room temperature. After one hour, more NH4SCN (1.0 g, 13.1 mmol) was added, followed by more Br2 (0.33 ml, 6.42 mmol) in AcOH (0.33 ml), dropwise with stirring. The reaction mixture was then heated to reflux for several minutes. Upon cooling to room temperature, solids were filtered and washed with AcOH, followed by H2O. The volume of the filtrate was reduced in vacuo and the pH adjusted to pH 9-10 with 1.0N NaOH. The resulting solids were filtered, washed with H2O, and dried under high vacuum to give 6-(6,7-dimethoxy-quinolin-4-yloxy)-5-fluoro-benzothiazol-2-ylamine (568 mg, 48%). 1H-NMR (400 MHz, DMSO): 8.45 (d, 1H), 7.82 (d, 1H), 7.73 (br s, 2H), 7.53 (s, 1H), 7.38 (m, 2H), 6.44 (d, 1H), 3.94 (s, 6H). LC/MS Calcd for [M+H]+ 372.1, found 372.2

Fuente