Reacción #634376

Ecuación de reacción

tributylphosphine

1,1′-(Azodicarbony)dipiperidine

3-(methylthio)-1-propanol

4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline

→

4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(3-methylthiopropoxy)quinazoline

Rendimiento 50.0%

Disolventes

methylene chloride

Condiciones de reacción

Tratamiento posterior

1. 1
   Otro(prepared
2. 2
   Otroat 5° C
3. 3
   workup.WAITfor 18 hours at ambient temperature
4. 4
   OtroThe insolubles were removed by filtration
5. 5
   Otrothe volatiles were removed from the filtrate by evaporation
6. 6
   OtroThe residue was purified by column chromatography
7. 7
   Lavadoeluting with ethyl acetate/methanol (100/0 increasing to 95/5)

Procedimiento

1,1′-(Azodicarbony)dipiperidine (1.56 g, 6.2 mmol) followed by 3-(methylthio)-1-propanol (0.32 ml, 3 mmol) was added to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (225 mg, 7.0 mmol), (prepared as described for the starting material in Example 48), and tributylphosphine (1.42 mL 6.1 mmol) in methylene chloride (20 ml) at 5° C. The mixture was stirred at 5° C. for 1 hour and then for 18 hours at ambient temperature. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with ethyl acetate/methanol (100/0 increasing to 95/5) to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(3-methylthiopropoxy)quinazoline (400 mg, 50%).

Fuente