Reacción #69770

Ecuación de reacción

3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenylamine

tetrahydrofuran

methylamine

isopropanol

→

target product

Rendimiento 38.7%

[4-(3-aminophenyl)-6,7-dimethoxyquinazolin-2-yl]methylamine

Rendimiento 38.7%

Disolventes

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato cool down to 25° C.
2. 2
   Concentraciónconcentrated under reduced pressure
3. 3
   workup.ADDITIONTo the residue were added 1.0 L of water and 4.0 L of chloroform
4. 4
   workup.STIRRINGthe mixture was stirred at 50° C. for 0.5 hours
5. 5
   Temperaturato cool down to 25° C
6. 6
   FiltraciónThe mixture was filtered through celite
7. 7
   Otroto remove the insoluble matter
8. 8
   Otrothe filtrate was transferred to separatory funnel
9. 9
   Otrothe organic layer was separated
10. 10
    workup.ADDITIONTo the organic layer were added 50.0 g of anhydrous magnesium sulfate and 20.0 g of activated carbon
11. 11
    workup.STIRRINGthe mixture was stirred at 50° C. for 1 hour
12. 12
    Temperaturato cool down to 25° C
13. 13
    FiltraciónThe mixture was filtered through celite
14. 14
    Otroto remove the insoluble matter
15. 15
    Concentraciónthe filtrate was concentrated under reduced pressure
16. 16
    workup.ADDITIONTo the residue was added 904 mL of chloroform
17. 17
    workup.STIRRINGthe mixture was stirred at 50° C. for 1 hour
18. 18
    workup.STIRRINGstirred overnight
19. 19
    workup.STIRRINGThen the mixture was stirred in an ice bath for 2 hours
20. 20
    Otroprecipitated crystals
21. 21
    Filtraciónwere filtered
22. 22
    Otrothe crystals were dried at 50° C. under reduced pressure

Procedimiento

Two hundred grams of crude 3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenylamine (content 124 g; 0.394 mol) was suspended in a mixed solution of 1.2 L of tetrahydrofuran and 0.6 L of isopropanol. To the mixture was added 1.2 L of a methylamine solution in methanol, and the mixture was stirred in a SUS autoclave at 90° C. for 15 hours. The reaction mixture was allowed to cool down to 25° C., and concentrated under reduced pressure. To the residue were added 1.0 L of water and 4.0 L of chloroform, and the mixture was stirred at 50° C. for 0.5 hours and allowed to cool down to 25° C. The mixture was filtered through celite to remove the insoluble matter, and the filtrate was transferred to separatory funnel and the organic layer was separated. To the organic layer were added 50.0 g of anhydrous magnesium sulfate and 20.0 g of activated carbon, and the mixture was stirred at 50° C. for 1 hour and allowed to cool down to 25° C. The mixture was filtered through celite to remove the insoluble matter, and the filtrate was concentrated under reduced pressure. To the residue was added 904 mL of chloroform, and the mixture was stirred at 50° C. for 1 hour and stirred overnight after turning off the heater. Then the mixture was stirred in an ice bath for 2 hours and precipitated crystals were filtered, and the crystals were dried at 50° C. under reduced pressure to yield 76.3 g of a target product. Yield: 38.7%

Fuente