Reaktion #69773

Reaktionsgleichung

4-chlorocarbonylbenzoic acid methyl ester

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

pyridine

dimethyl sulfoxide

→

titled compound

Ausbeute 53.2%

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

Ausbeute 53.2%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe mixture was partitioned between a mixed solvent
2. 2
   Sonstigethe organic layer was separated
3. 3
   ExtraktionThe water layer was further extracted with a mixed solvent
4. 4
   WaschenThe 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
   Trocknendried over anhydrous magnesium sulfate
6. 6
   SonstigeThe desiccant was removed by filtration with 100 g of a basic silica gel pad
7. 7
   Waschenby well washing with 2,000 mL of ethyl acetate
8. 8
   EinengenThe combined eluent was concentrated under reduced pressure
9. 9
   Sonstigethe obtained crude product
10. 10
    Sonstigetriturated in a mixed solvent
11. 11
    FiltrationThe precipitated crystals were collected by filtration
12. 12
    Waschenwashed twice with 100 mL of diethyl ether
13. 13
    Sonstigedried under aeration at 50° C. for 5 hours

Vorschrift

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%).

Quelle