A quinazoline-containing chalcone phosphonate derivative, its preparation method and use
A technology of chalcone phosphonic acid and quinazoline, which is applied to quinazoline-containing chalcone phosphonate derivatives, the fields of preparation and use thereof, and can solve the problem of low selectivity and poor biological activity selectivity. Advanced problems, to achieve the effect of good activity
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Embodiment 1
[0044] The preparation method of diethyl (3-OXO-1-phenyl-3-(4-(quinazoline-4-amino) phenyl) propyl) phosphonate (compound number is a), comprises the following steps:
[0045] (1) Preparation of quinazoline-4(3H)-one:
[0046] In a 100mL three-necked flask, add 9.30g of methyl anthranilate, 14.9g of formamide and 4mL of formic acid, mix and heat to 130-140°C, stop the reaction after 7 hours of reaction, slowly add 30mL of water, cool to room temperature, and a large amount of The solid precipitated and was filtered by suction to obtain a white solid, which was recrystallized from absolute ethanol to obtain 7.50 g of the white flocculent target product with a yield of 78.0%.
[0047] (2) The preparation of 4-chloroquinazoline:
[0048] In a 100mL three-necked flask, add 2.0g of quinazolin-4(3H)-one, 15mL of thionyl chloride, 8mL of 1,2-dichloroethane, 1mL of N,N-dimethylformamide, and start Heat to reflux, distill off the solvent under reduced pressure after 4h, add 40mL of c...
Embodiment 2
[0056] The preparation method of diethyl (1-(3-bromophenyl)-3-OXO-3-(4-(quinazoline-4-amino)phenyl)propyl) phosphonate (compound number is b) , including the following steps:
[0057] (1) Preparation of quinazoline-4(3H)-one:
[0058] As in the first (1) step of Example 1.
[0059] (2) The preparation of 4-chloroquinazoline:
[0060] As in embodiment 1 (2) step.
[0061] (3) Preparation of 1-(4-(quinazoline-2-amino)phenyl)ethanone:
[0062] As in embodiment 1 (3) step.
[0063] (4) Preparation of (E)-3-(3-bromophenyl)-1-(4-(quinazoline-4-amino)phenyl)prop-2-en-1-one:
[0064] As in the (4) step of embodiment 1, the difference is that 3-bromobenzaldehyde is used as raw material;
[0065] (5) Preparation of diethyl (1-(3-bromophenyl)-3-OXO-3-(4-(quinazoline-4-amino)phenyl)propyl) phosphonate:
[0066] As in step (5) of Example 1, the difference is that (E)-3-(3-bromophenyl)-1-(4-(quinazoline-4-amino)phenyl)prop-2-ene- 1-ketone as raw material;
Embodiment 3
[0068] The preparation method of diethyl (2-chlorophenyl)-3-OXO-3-(4-(quinazoline-4-amino) phenyl) propyl) phosphonate (compound number is c), comprises following step:
[0069](1) Preparation of quinazoline-4(3H)-one:
[0070] As in the first (1) step of Example 1.
[0071] (2) The preparation of 4-chloroquinazoline:
[0072] As in embodiment 1 (2) step.
[0073] (3) Preparation of 1-(4-(quinazoline-2-amino)phenyl)ethanone:
[0074] As in embodiment 1 (3) step.
[0075] (4) Preparation of (E)-3-(2-chlorophenyl)-1-(4-(quinazoline-4-amino)phenyl)prop-2-en-1-one:
[0076] As in the (4) step of embodiment 1, the difference is that 2-chlorobenzaldehyde is used as raw material;
[0077] (5) Preparation of diethyl (2-chlorophenyl)-3-OXO-3-(4-(quinazoline-4-amino)phenyl)propyl) phosphonate:
[0078] As in step (5) of Example 1, the difference is that (E)-3-(2-chlorophenyl)-1-(4-(quinazoline-4-amino)phenyl)prop-2-ene-1 - ketone as raw material;
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