Phthalimide derivative as well as preparation method and application thereof

[0103] Example 1 Compound H1: 2-(4-morpholinylphenyl)-1,3-dioxoisoindole-4-carboxamide

[0104] The first step, the preparation of 3-carboxyphthalic anhydride (2)

[0105]

[0106] 2.1 g (10 mmol) of 1,2,3-benzenetricarboxylic acid (1) and 30 mL of THF were added to a 100 mL single-necked round-bottomed flask, shaken and shaken. The solvent was distilled off under reduced pressure to make the raw material adherent. Put the open-top round-bottomed flask into a 150°C oil bath for dry burning for 6 hours, and during the process, it is obvious that water droplets are formed on the bottle wall. After the completion of the reaction, the reaction was lowered to room temperature to obtain 21.9 g of white solid with a yield of 99%; 1 H NMR (400MHz, DMSO-d 6 )δ: 7.77(d, J=7.7Hz, 2H), 7.44(t, J=7.7Hz, 1H); 13 C NMR (101MHz, DMSO-d 6 )δ: 169.92, 169.07, 136.26, 131.57, 129.04.

[0107] The second step, the preparation of 2-(4-morpholinylphenyl)-1,3-dioxoisoindole-4-carboxylic acid (

[0113] Example 2 Compound H2: 2-(4-(4-methylpiperazin-1-yl)phenyl)-1,3-dioxoisoindole-4-carboxamide

[0114]

[0115] The reaction conditions for preparing compound H2 are similar to those of compound H1, and the second step of the reaction uses 3-carboxyphthalic anhydride and 4-(4-methylpiperazine)aniline as raw materials. Solid (39.2% yield). 1 H NMR (400MHz, Chloroform-d) δ: 9.98 (s, 1H), 8.76 (dd, J=8.0, 1.2Hz, 1H), 8.13 (dd, J=7.3, 1.2Hz, 1H), 7.92 (t, J=7.7Hz, 1H), 7.27(d, J=6.9Hz, 2H), 7.07~7.00(d, J=8.9Hz, 2H), 6.00(s, 1H), 3.29(t, J=5.1Hz, 4H), 2.61~2.56(m, 4H), 2.37(s, 3H); 13 C NMR (101MHz, DMSO-d 6 )δ: 168.11, 167.08, 166.88, 138.55, 135.21, 134.57, 134.41, 134.21, 133.68, 130.24, 129.51, 125.42, 120.77, 57.54, 53.92, 44.32; HR-MS (ESI-Calc for C for C) m / z 20 H 20 N 4 O 3 {[M+H] +}365.1608, found365.1610.

[0116] Example 3 Compound H3: 2-(4-(trifluoromethoxy)phenyl)-1,3-dioxoisoindole-4-carboxamide

[0117]

[0118] The reaction conditions for preparing compound H3 are similar to those of compound H1, and the second step reaction uses 3-carboxyphthalic anhydride and 4-trifluoromethoxyaniline as raw materials. Solid (47.3% yield). 1 H NMR (400MHz, DMSO-d 6 )δ13.40(s, 1H), 8.39(s, 1H), 8.35–8.23(m, 2H), 7.91(dd, J=8.6, 1.4Hz, 1H), 7.48(s, 2H), 7.25(d , J=5.1Hz, 1H), 7.14(t, J=7.8Hz, 1H), 6.94(d, J=7.5Hz, 1H), 6.88(t, J=1.9Hz, 1H), 6.74(s, 2H ),6.53(dd,J=8.0,2.2Hz,1H),5.66(d,J=5.1Hz,1H),2.76(d,J=4.9Hz,3H). 13 C NMR (101MHz, DMSO-d 6 )δ164.34,164.15,159.51,150.68,143.03,142.06,138.03,135.62,131.25,129.60,122.25,121.43,119.98,119.92,114.78,112.44,109.64,109.27,106.78,30.30.HRMS(ESI-TOF)m / z Calcd for C 20 H 19 N 6 [M+H] + :343.1672,found:343.1678.