Reacción #69773

Ecuación de reacción

4-chlorocarbonylbenzoic acid methyl ester

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

pyridine

dimethyl sulfoxide

→

titled compound

Rendimiento 53.2%

methyl N-[3-(6,7-dimethoxy-2-methylaminoquinazolin-4-yl)phenyl]terephthalamic acid

Rendimiento 53.2%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe mixture was partitioned between a mixed solvent
2. 2
   Otrothe organic layer was separated
3. 3
   ExtracciónThe water layer was further extracted with a mixed solvent
4. 4
   LavadoThe combined organic layer was then washed with 1,000 mL of a saturated sodium hydrogencarbonate solution and 1,000 mL of brine in this order
5. 5
   Secadodried over anhydrous magnesium sulfate
6. 6
   OtroThe desiccant was removed by filtration with 100 g of a basic silica gel pad
7. 7
   Lavadoby well washing with 2,000 mL of ethyl acetate
8. 8
   ConcentraciónThe combined eluent was concentrated under reduced pressure
9. 9
   Otrothe obtained crude product
10. 10
    Otrotriturated in a mixed solvent
11. 11
    FiltraciónThe precipitated crystals were collected by filtration
12. 12
    Lavadowashed twice with 100 mL of diethyl ether
13. 13
    Otrodried under aeration at 50° C. for 5 hours

Procedimiento

To a solution of 16.8 g of [4-(3-aminophenyl)-6,7-dimethoxyquinazolin-2-yl]methylamine and 8.6 g of pyridine dissolved in 300 mL of tetrahydrofuran was added 11.8 g of 4-chlorocarbonylbenzoic acid methyl ester at room temperature, followed by stirring for 24 hours. To the reaction mixture was added 100 mL of dimethyl sulfoxide, the mixture was partitioned between a mixed solvent consisting of 2,000 mL of ethyl acetate and 1,000 mL of tetrahydrofuran, and 1,000 mL of a saturated sodium hydrogencarbonate solution, and the organic layer was separated. The water layer was further extracted with a mixed solvent consisting of 500 mL of ethyl acetate and 500 mL of tetrahydrofuran. The combined organic layer was then washed with 1,000 mL of a saturated sodium hydrogencarbonate solution and 1,000 mL of brine in this order, and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration with 100 g of a basic silica gel pad, followed by well washing with 2,000 mL of ethyl acetate. The combined eluent was concentrated under reduced pressure, and the obtained crude product was suspended and triturated in a mixed solvent consisting of 100 mL of tetrahydrofuran and 500 mL of diethyl ether. The precipitated crystals were collected by filtration, washed twice with 100 mL of diethyl ether, and dried under aeration at 50° C. for 5 hours to yield 13.8 g of the crystals of the titled compound (yield: 53.2%).

Fuente