A kind of indazole compound and its preparation method and application
A technology of compound and indazole, which is applied in the field of indazole compound and its preparation and application, and can solve problems such as unsuccessful development
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Embodiment 1
[0084] This embodiment is used to illustrate the preparation method of the indazole compound of the present invention
[0085] Indazole compounds of the present invention are synthesized through the following synthetic routes:
[0086]
[0087] 1) Synthesis of compound 2
[0088] In a 500 mL three-necked flask, 2,4-difluoroaniline (100 mmol) was dissolved in 200 mL of concentrated hydrochloric acid. Keeping the external temperature of the system at -9°C, a mixed solution of sodium nitrite (8.28 g, 120 mmol) and water (50 mL) was slowly added dropwise to the above system, and the addition was completed within 25 minutes. After stirring for about 1 hour, the SnCl 2 A mixed solution of (45.1g, 200mmol) and concentrated hydrochloric acid (100mL) was slowly added dropwise to the above system, and the dropwise addition was completed within 2h. Afterwards, the ice-salt bath was continued to keep the reaction at low temperature for 2 hours, and then filtered, and the filter resi...
Embodiment 2
[0117] This embodiment is used to illustrate the preparation method of the indazole compound of the present invention
[0118] According to the method in Example 1, the difference is that in step 1, 2,4-difluoroaniline is replaced by 2,4-dichloroaniline, to obtain the target compounds I-15~I-27 shown in Table 1 .
[0119] The confirmed data of compounds I-15~I-27 are as follows:
[0120] I-15: solid; m.p.155-156°C. 1 H NMR (600MHz, CDCl 3 )δ7.90(s,1H),7.86(s,1H),4.24(q,J=7.2Hz,2H),4.16(s,2H),2.74(d,J=6.0Hz,2H),2.55( d, J=6.0Hz, 2H), 1.85(q, J=6.0Hz, 4H), 1.29(t, J=7.2Hz, 3H).ESI-MS: 464.1(M+Na) + .
[0121] I-16: solid; m.p.102-103°C. 1 H NMR (600MHz, CDCl 3 )δ7.88(s,1H),7.87(s,1H),4.19(q,J=7.1Hz,2H),3.61(t,J=7.2Hz,2H),2.91(t,J=7.2Hz, 2H), 2.75(t, J=6.0Hz, 2H), 2.54(t, J=6.0Hz, 2H), 1.85(dd, J=6.6Hz, 4H), 1.28(t, J=7.2Hz, 3H) .ESI-MS: 478.2 (M+Na) + .
[0122] I-17: solid; 1 H NMR (600MHz, CDCl 3 )δ7.88(s,1H),7.86(s,1H),4.15(q,J=7.2Hz,2H),3.42(t,J=7.2Hz,2H),2.74(t...
Embodiment 3
[0134] This embodiment is used to illustrate the preparation method of the indazole compound of the present invention
[0135] According to the method in Example 1, the difference is that 2,4-difluoroaniline is replaced by 2-bromo-4-fluoroaniline in step 1 to obtain the target compounds I-28~I- 40.
[0136] The confirmed data of compounds I-28~I-40 are as follows:
[0137] I-28: solid; m.p.108-110°C. 1 H NMR (600MHz, CDCl 3 )δ8.07(s,1H),7.85(s,1H),4.24(q,J=7.2Hz,2H),4.16(s,2H),2.75(s,2H),2.54(s,2H), 1.85(q, J=6.0Hz, 4H), 1.29(t, J=7.2Hz, 3H).ESI-MS: 486.2(M+H) + .
[0138] I-29: solid; m.p.108-109°C. 1 H NMR (600MHz, CDCl 3 )δ8.05(s,1H),7.86(s,1H),4.18(q,J=7.2Hz,2H),3.61(t,J=7.2Hz,2H),2.91(t,J=7.2Hz, 2H), 2.74(t, J=6.0Hz, 2H), 2.54(t, J=6.0Hz, 2H), 1.85(q, J=6.0Hz, 4H), 1.27(t, J=7.2Hz, 3H) .ESI-MS:522.1(M+Na) + .
[0139] I-30::Oil. 1 H NMR (600MHz, CDCl 3 )δ8.05(s,1H),7.85(s,1H),4.15(q,J=7.2Hz,2H),3.42(t,J=7.2Hz,2H),2.76(t,J=6.0Hz, 2H), 2.54(t, J=6.0Hz, 2H), 2....
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