A method for synthesizing B(4)-aryl-B(9)-amide-o-carborane derivatives

Abstract

The present invention relates to a method for synthesizing a B(4)-aryl-B(9)-amide-o-carborane derivative. The method discloses a method for synthesizing a B(9)-amide-o-carborane derivative. The method comprises the following steps: using B(9)-amide-o-carborane as a raw material, reacting in tetrahydrofuran at 50° C. for 24 hours under an argon atmosphere with 10 mol% Pd(MeCN)4(BF4)2 as a catalyst, 2 eq Cu(OAc)2 and 1 eq Ag2O as oxidants, and selectively oxidative coupling of potassium aryltrifluoroborate with B(4)-H to prepare the B(4)-aryl-B(9)-amide-o-carborane derivative. The method has the advantages of simple operation and a wide range of substrate applicability.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthetic chemistry and relates to a method for synthesizing a B(4)-aryl-B(9)-amide-o-carborane derivative. Background Art

[0002] In the field of medicine, it can be used in boron neutron capture therapy, which is one of the methods to achieve effective precision treatment in cancer treatment. In addition, in drug discovery, structural diversity is a key factor in therapeutic innovation. Independent or "first-in-class" molecular entities that have not been used in drug design before can discover new therapies with significant clinical benefits. Despite the high level of investment in drug research and development, only relatively few new molecular entities are approved for clinical use each year, and carborane can provide structural diversity of compounds that are different from the skeletons of conventional compounds, which promotes the development of new and effective biologically active compounds. In recent years, studies have shown that replacing phenyl groups with carborane can improve drug efficacy by promoting special hydrophobic interactions with protein binding sites and promoting passage through the blood-brain barrier. Carborane is more hydrophobic than adamantyl and phenyl groups. Their combination with drug analogs can favorably regulate some physical and chemical properties of the compound. Moreover, the amide group contained in the molecule can serve as an activation group for the drug target, while improving the bioavailability and stability of the drug. 1 It has been reported that amide-containing carborane derivatives can interact with receptors or enzymes such as epoxide hydrolase receptors, translocase receptors, nicotinamide phosphoribosyltransferase, and cyclooxygenase, and exhibit significant biological activities. 2 In the future, carborane will have more applications in drug discovery, chemical biology, and biomolecular imaging.

[0003] Since o-carborane contains ten BH bonds with similar chemical environments and little difference in reactivity, its selective functionalization is very difficult. The present invention introduces an amide at the B(9) position, using the amide as a positioning group to control the selectivity of the BH bond on the one hand, and on the other hand, using the electron-withdrawing effect of the amide to induce the activation of the B(4)-H bond. On this basis, potassium aryl trifluoroborate is used as a coupling unit, and palladium-catalyzed oxidative coupling is used to achieve selective arylation of B(4)-H, providing a material and technical basis for exploring the application of B(4)-aryl-B(9)-amide-o-carborane derivatives in the preparation of anti-tumor drugs.

[0004] This method provides an economical and efficient method for the selective functionalization of the BH bond of o-carborane, lays a theoretical and technical foundation for the further design of the selective functionalization of B(9)-amide-o-carborane B(4)-H, and provides a material basis for exploring the application of B(4)-aryl-B(9)-amide-o-carborane in related disciplines.

[0005] 1. Kumari, S.; Carmona, AV; Tiwari, AK; Trippier, PC. Amide BondBioisosteres: Strategies, Synthesis, and Successes. J. Med. Chem. 2020, 63, 12290-12358.

[0006] 2. Marfavi, A.; Kavianpour, P.; Rendina, LM, Carboranes in drug discovery, chemical biology and molecular imaging. Nat Rev Chem. 2022, 6, 486-504. Summary of the Invention

[0007] The purpose of the present invention is to utilize the electron-withdrawing effect of amide to induce the activation of B(4)-H, use potassium aryl trifluoroborate as the aryl source, and achieve the selective arylation of B(9)-amide-o-carborane B(4)-H under mild conditions, thereby obtaining a series of B(4)-aryl-B(9)-amide-o-carborane derivatives.

[0008] In a first aspect, the present invention provides a B(4)-aryl-B(9)-amide-o-carborane derivative, which is represented by the following general formula (1).

[0009]

[0010] Wherein, R1 is one of phenyl, substituted phenyl, benzyl, benzylnaphthalene or cyclopropyl;

[0011] The R2 is one of phenyl, substituted phenyl or naphthyl.

[0012] Preferably, the substituent of the substituted phenyl group is one of halogen, methyl, methoxy, trifluoromethyl, tert-butyl and acetyl.

[0013] Preferably, the substituent of the substituted phenyl group in R1 is one of halogen, methyl, methoxy, trifluoromethyl, and tert-butyl; the substituent of the substituted phenyl group in R2 is one of halogen, methyl, methoxy, trifluoromethyl, tert-butyl, and acetyl.

[0014] In a second aspect, the present invention provides a method for preparing a B(4)-aryl-B(9)-amide-o-carborane derivative, wherein the method for preparing the derivative is represented by the following general formula (2):

[0015]

[0016] Using B(9)-amide-o-carborane as raw material, in an argon atmosphere, with 10 mol% Pd(MeCN)4(BF4)2 as catalyst, 2 eq Cu(OAc)2 and 1 eq Ag2O as oxidants, the reaction was carried out in tetrahydrofuran at 50°C for 24 h. The selective oxidative coupling of potassium aryl trifluoroborate with B(4)-H was used to efficiently achieve the diversified synthesis of B(4)-aryl-B(9)-amide-o-carborane derivatives.

[0017] Wherein, R1 is one of phenyl, substituted phenyl, benzyl, benzylnaphthalene or cyclopropyl;

[0018] The R2 is one of phenyl, substituted phenyl or naphthyl.

[0019] Preferably, the substituent of the substituted phenyl group is one of halogen, methyl, methoxy, trifluoromethyl, tert-butyl and acetyl.

[0020] Preferably, the substituent of the substituted phenyl group in R1 is one of halogen, methyl, methoxy, trifluoromethyl, and tert-butyl; the substituent of the substituted phenyl group in R2 is one of halogen, methyl, methoxy, trifluoromethyl, tert-butyl, and acetyl.

[0021] Preferably, the reaction temperature is 50°C.

[0022] Preferably, the reaction atmosphere is argon.

[0023] Preferably, the method for preparing the B(4)-aryl-B(9)-amide-o-carborane derivative further comprises a method for preparing a raw material 9-amide-o-carborane derivative, the method comprising:

[0024] (1) reacting an o-carborane derivative with dichloromethane, I2 and AlCl3 catalyst to obtain a 9-Io-carborane derivative;

[0025] (2) 9-Io-carborane derivatives react with benzamide, Pd2(dba)3, K3PO4, DavePhos and toluene to obtain 9-amide-o-carborane derivatives;

[0026] Preferably, the method further comprises:

[0027] (3) Filtration, concentration, and separation: After the reaction in step (2) is completed, the system temperature is cooled to room temperature, and then filtered through a short silica gel column using ethyl acetate as the eluent. The filtrate is concentrated under reduced pressure and then purified by column chromatography using petroleum ether / ethyl acetate = 5:1 as the eluent to obtain a B(4)-aryl-B(9)-amide-o-carborane derivative.

[0028] Preferably, taking 9-Io-carborane as an example, the formula is:

[0029] Step 1: reacting an o-carborane derivative with dichloromethane, I2 and AlCl3 catalyst to obtain a 9-Io-carborane derivative;

[0030]

[0031] Under argon, an o-carborane derivative (1.44 g, 10 mmol), dry dichloromethane (DCM) (30 mL), I2 (2.54 g, 10 mmol), and a catalytic amount of AlCl3 were added to a dry 100 mL round-bottom flask. The magnetic stirrer was adjusted to a desired speed and the reaction flask was placed in a 40°C oil bath. The reaction was monitored by TLC. After completion, the reaction was quenched with water. The reaction system was extracted with ethyl acetate, washed several times with saturated aqueous NaHCO3 and NaCl solutions, and dried over anhydrous Na2SO4. After concentration under reduced pressure, the crude product was recrystallized to yield 2.45 g of the desired product in a 90% yield.

[0032] Step 2: 9-Io-carborane reacts with benzamide, Pd2(dba)3, K3PO4, DavePhos and toluene to obtain 9-amide-o-carborane derivatives;

[0033]

[0034] Under argon, a dry 100 mL round-bottom flask was charged with 9-Io-carborane (1 g, 3.7 mmol), benzamide (1343 mg, 11.1 mmol), Pd2(dba)3 (84 mg, 2.5 mol%), K3PO4 (3.92 g, 18.5 mmol), davephos (72 mg, 0.05 mmol), and 15 mL of toluene. The stirrer speed was adjusted and the reaction flask was placed in a 100°C oil bath for reaction. The reaction progress was monitored by TLC. After the reaction was completed and the system was cooled to room temperature, it was filtered through a short silica gel column using ethyl acetate as the eluent. The filtrate was concentrated under reduced pressure and purified by column chromatography using petroleum ether / ethyl acetate = 5:1 as the eluent. 537.2 mg of the product was obtained by column chromatography with a yield of 55%.

[0035] In a third aspect, the present invention provides the use of the B(4)-aryl-B(9)-amide-o-carborane derivative described in the first aspect in the preparation of anti-tumor drugs.

[0036] Beneficial effects:

[0037] 1) The method for arylating B(9)-amide-o-carborane B(4)-H designed in the present invention is simple to operate. The reaction uses stable potassium phenyltrifluoroborate as the aryl source and achieves selective arylation of B(4)-H with excellent regioselectivity under anhydrous conditions.

[0038] 2) The present invention provides a novel method for the selective functionalization of o-carborane, and offers new ideas for further designing the selective functionalization of o-carborane B(4)-H and the diversified synthesis of o-carborane derivatives. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 is the general formula of B(4)-aryl-B(9)-amide-o-carborane derivative;

[0040] Figure 2 is the general formula for the preparation of B(4)-aryl-B(9)-amide-o-carborane derivatives;

[0041] Figure 3 A method for preparing 9-Io-carborane derivatives;

[0042] Figure 4 A method for preparing 9-amide-o-carborane derivatives;

[0043] Figure 5 The reaction formula for preparing B(4)-aryl-B(9)-amide-o-carborane is shown below:

[0044] Figure 6 Reaction conditions for the preparation of B(4)-aryl-B(9)-amide-o-carborane;

[0045] Figure 7 It is a substrate expansion for B(4)-aryl-B(9)-amide-o-carborane derivatives;

[0046] Figure 8 is the preparation reaction formula of compound 2a;

[0047] Figure 9 is the preparation reaction formula of compound 2b;

[0048] Figure 10 is the preparation reaction formula of compound 2c;

[0049] Figure 11 is the preparation reaction formula of compound 2d;

[0050] Figure 12 is the preparation reaction formula of compound 2e;

[0051] Figure 13 is the preparation reaction formula of compound 2f;

[0052] Figure 14 is the preparation reaction formula of compound 2g;

[0053] Figure 15 is the reaction formula for the preparation of compound 2h;

[0054] Figure 16 is the preparation reaction formula of compound 2i;

[0055] Figure 17 is the preparation reaction formula of compound 2j;

[0056] Figure 18 is the preparation reaction formula of compound 2k;

[0057] Figure 19 is the preparation reaction formula of compound 21;

[0058] Figure 20 is the reaction formula for the preparation of compound 2m;

[0059] Figure 21 is the preparation reaction formula of compound 2n;

[0060] Figure 22 is the reaction formula for the preparation of compound 2o;

[0061] Figure 23 is the reaction formula for the preparation of compound 2p;

[0062] Figure 24 is the preparation reaction formula of compound 2q;

[0063] Figure 25 is the preparation reaction formula of compound 2r;

[0064] Figure 26 is the preparation reaction formula of compound 2s;

[0065] Figure 27 is the preparation reaction formula of compound 2t;

[0066] Figure 28 is the reaction formula for the preparation of compound 2u;

[0067] Figure 29 is the preparation reaction formula of compound 2v;

[0068] Figure 30 is the preparation reaction formula of compound 2w;

[0069] Figure 31 is the preparation reaction formula of compound 2y;

[0070] Figure 32 This is the reaction formula for the preparation of compound 2z. DETAILED DESCRIPTION

[0071] Example 1 Evaluation of different preparation processes:

[0072] Taking B(9)-amide-o-carborane (1a) and potassium phenyltrifluoroborate as raw materials to prepare B(4)-aryl-B(9)-amide-o-carborane (2a) as an example, the reaction conditions were evaluated as follows. The reaction conditions are shown in Table 1 below:

[0073]

[0074] Table 1 Reaction conditions

[0075] Entry Catalyst Oxidant Solvent <![CDATA[Yield b ]]> 1 <![CDATA[Pd(OAc)2]]> <![CDATA[Cu(OAc)2]]> THF 42.8 2 <![CDATA[Pd(OAc)2]]> <![CDATA[Cu(OAc)2]]> toluene 23.3 3 <![CDATA[Pd(OAc)2]]> <![CDATA[Cu(OAc)2]]> <![CDATA[CH3CN]]> 32.2 4 <![CDATA[Pd(OAc)2]]> <![CDATA[Cu(OAc)2]]> HFIP 26.7 5 <![CDATA[Pd(MeCN)2Cl2]]> <![CDATA[Cu(OAc)2]]> THF 33.3 6 <![CDATA[Pd(TFA)2]]> <![CDATA[Cu(OAc)2]]> THF 36.6 7 <![CDATA[Pd(MeCN)4(BF4)2]]> <![CDATA[Cu(OAc)2]]> THF 50 8 <![CDATA[Pd(MeCN)4(BF4)2]]> <![CDATA[Ag2O]]> THF 53.2 9 <![CDATA[Pd(MeCN)4(BF4)2]]> <![CDATA[Ag2CO3]]> THF 40.4 10 <![CDATA[Pd(MeCN)4(BF4)2]]> <![CDATA[AgNO3]]> THF 46 11 <![CDATA[Pd(MeCN)4(BF4)2]]> AgOAc THF 51.5 12 <![CDATA[Pd(MeCN)4(BF4)2]]> <![CDATA[AgBF4]]> THF 45.6 13 <![CDATA[Pd(MeCN)4(BF4)2]]> <![CDATA[AgOAc+Cu(OAc)2 d ]]> THF 68.9 14 <![CDATA[Pd(MeCN)4(BF4)2]]> <![CDATA[Ag2O+Cu(OAc)2 d ]]> THF <![CDATA[75(69 c )]]>

[0076] Note: All reactions were performed using 0.1 mmol of 1a, 0.3 mmol of potassium phenyltrifluoroborate, 10 mol% of catalyst, 0.2 mmol of oxidant, and 1 mL of solvent under argon atmosphere for 24 h. b GC yield, c Isolated yield, d 0.2mmol silver salt and 0.1mmol copper salt.

[0077] The results showed that B(4)-aryl-B(9)-amide-o-carborane derivatives could be prepared under the above different preparation process conditions. Among them, taking B(4)-aryl-B(9)-amide-o-carborane (2a) as an example, the optimal synthesis conditions were the reaction conditions corresponding to number 14 in Table 1: B(9)-amide-o-carborane 1a (0.1mmol, 26.3mg), potassium phenyltrifluoroborate (0.3mmol, 55.2mg), Pd(MeCN)4(BF4)2 (10mol%, 4.5mg) as catalyst, Ag2O (2eq, 46mg) and Cu(OAc)2 (1eq, 20mg) as oxidants, and the reaction was carried out in 1mLTHF at 50℃ for 24h.

[0078] Example 2 Substrate expansion:

[0079] According to the reaction conditions of the above different preparation processes, after replacing other reaction substrates, the reaction formula and the corresponding synthetic products are as follows:

[0080]

[0081] The specific synthesis method and results are as follows:

[0082] 1. Preparation of compound 2a:

[0083]

[0084] Under argon atmosphere, B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol), dry THF (1 mL), potassium phenyltrifluoroborate (55.2 mg, 0.3 mmol), palladium tetraacetonitrile tetrafluoroborate (4.5 mg, 10 mol%), silver oxide (46 mg, 0.2 mmol), and copper acetate (20 mg, 0.1 mmol) were added to a dry 10 mL round-bottom flask in sequence. The round-bottom flask was placed in a 50° C. oil bath for 24 h (the reaction equation is shown above). The reaction was monitored by TLC. After the reaction, the system was filtered with filter paper, concentrated under reduced pressure, and then purified by column chromatography using petroleum ether / ethyl acetate = 4:1 to 3:1 as eluent. Column chromatography gave 23.4 mg of product 2a with a yield of 69%, as expected.

[0085] NMR data: 1HNMR (500MHz, CDCl3, ppm): δ7.63-7.61 (m, 4H), 7.43-7.39 (m, 1H), 7.35-7.28 (m, 5H), 5.69 (s, 1H), 3.71 (s, 2H); 13C{1H}NMR (125MHz, CDCl3, ppm): δ169.3, 135.8, 134 .1,131.0,128.9,128.3,128.0,127.0,52.3,47.5; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.5(1B),-2.3(2B),-3.7(2B),-9.8(2B),-14.2(1B),-16.8(2B); HRMS(ESI)m / zcalcd for C 15 H 22 B 10 NO + (M+H) + 340.26991,found 340.27090.

[0086] 2. Preparation of compound 2b:

[0087]

[0088] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 3-fluorophenyl trifluoroborate (60.6 mg, 0.3 mmol). The other methods were the same as those described in the above 1.

[0089] (The reaction equation is shown above). Column chromatography separation gave 19.7 mg of product 2b with a yield of 58%, which was in line with expectations.

[0090] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ7.75-7.74 (d, 2H, J = 12 Hz), 7.63-7.62 (m, 2H), 7.54-7.53 (d, 2H, J = 12 Hz), 7.44-7.41 (m, 1H), 7.37-7.34 (m, 2H), 5.70 (s, 1H), 3.74 (s, 2H); 13C{1H} NMR (150 MHz, CDCl3, ppm): δ169.2, 163.3-161.7 (J = 245 Hz),135.7,131.1,129.8-129.7(J=6Hz),129.7,128.4,127.0,120.6-120.5(J=21Hz),115.9-115.8(J=20Hz),52.3,47 .5; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.6(1B),-2.3(1B),-4.4(2B),-9.9(2B),-14.4(1B),-17.1(3B); HRMS(ESI)m / z calcd for C 15 H 19 B 10 FNO - (MH) - 357.24230,found 357.24359.

[0091] 3. Preparation of compound 2c

[0092]

[0093] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above step 1 was replaced with potassium 4-fluorophenyl trifluoroborate (60.6 mg, 0.3 mmol). The other procedures were the same as those described in the above step 1 (the reaction equation is shown above). Column chromatography was performed to obtain 15.9 mg of the product 2c in a yield of 47%, which was in line with the expected result.

[0094] NMR data: 1H NMR (600 MHz, CDCl 3 , ppm): δ 7.63-7.59 (m, 4H), 7.43-7.41 (dd, 1H, J = 12 Hz), 7.36-7.33 (dd, 2H, J = 12 Hz), 7.00-6.97 (dd, 2H, J = 12 Hz), 5.68 (s, 1H), 3.72 (s, 1H), 3.68 (s, 1H); 13C{1H} NMR (150 MHz, CDCl 3 , ppm): δ 169. 3,164.5-162.8(J=248Hz),136.1-136.1(J=9Hz),131.2,128.4,127.0,115.1-115.0(21Hz),52.5,47.5; 11B{ 1H}NMR (160MHz, CDCl3, ppm): δ6.6(1B),-2.3(2B),-3.9(2B),-9.8(2B),-14.7(1B),-17.0(2B); HRMS(ESI)m / z calcd for C 15 H 19 B 10 FNO - (MH) - 357.24230,found 357.24356.

[0095] 4. Preparation of Compound 2d

[0096]

[0097] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 4-chlorophenyl trifluoroborate (65.5 mg, 0.3 mmol). The other methods were the same as described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 15.7 mg of the product 2d with a yield of 42%, which was in line with expectations.

[0098] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ7.63-7.62 (d, 2H, J = 6 Hz), 7.56-7.54 (d, 2H, J = 6 Hz), 7.44-7.41 (m, 1H), 7.36-7.34 (m, 2H), 7.27-7.26 (m, 2H), 5.68 (s, 1H), 3.72 (s, 1H), 3.69 (s, 1H); 13C{1H} NMR (150 M Hz, CDCl3, ppm): δ169.3,135.6,135.5,135.4,131.2,128.4,128.2,127.0,52.4,47.5; 11B{1H}NMR(1 60MHz, CDCl3, ppm): δ6.5(1B),-2.3(2B),-4.1(2B),-9.8(2B),-14.4(1B),-17.1(2B); HRMS(ESI)m / z calcd for C 15 H 19 B 10 ClNO - (MH) - 373.21275,found373.21262.

[0099] 5. Preparation of compound 2e

[0100]

[0101] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above step 1 was replaced with potassium 3-bromophenyl trifluoroborate (78.9 mg, 0.3 mmol). The other procedures were the same as those described in the above step 1 (the reaction equation is shown above). Column chromatography was performed to obtain 15.7 mg of the product 2e in a yield of 38%, which was in line with the expected result.

[0102] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ7.73 (s, 1H), 7.65-7.61 (m, 2H), 7.55-7.54 (d, 1H, J = 6 Hz), 7.46-7.41 (m, 2H), 7.37-7.33 (m, 2H), 7.17-7.15 (dd, 1H, J = 6 Hz), 5.69 (s, 1H), 3.72 (s, 2H); 13C{1H} NMR (150 MHz , CDCl3, ppm): δ169.4,136.6,132.7,132.0,131.2,129.8,128.4,127.0,122.6,52.2,47.5; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.5(1B),-2.3(2B),-4.6(2B),-9.8(2B),-14.3(1B),-16.9(2B); HRMS(ESI)m / z calcd forC 15 H 19 B 10 BrNO - (MH) - 416.16587,found 416.16794.

[0103] 6. Preparation of Compound 2f

[0104]

[0105] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 4-bromophenyl trifluoroborate (78.9 mg, 0.3 mmol). The other methods were the same as described in the above 1 (the reaction equation is shown above). The product 2f was separated by column chromatography to obtain 16.6 mg of the product 2f with a yield of 40%, which was in line with the expectation.

[0106] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ 7.64-7.62 (m, 2H), 7.50-7.48 (m, 2H), 7.44-7.41 (m, 3H), 7.37-7.33 (m, 2H), 5.68 (s, 1H), 3.71 (s, 1H), 3.68 (s, 1H); 13C{1H} NMR (150 MHz, CDCl3, ppm): δ169.2,135.8,135.6,131.2,131.2,128.4,127.0,123.9,52.3,47.5; 11B{1H}NMR (160MHz, C DCl3, ppm): δ6.6(1B),-2.2(2B),-4.0(2B),-9.8(2B),-14.4(1B),-17.0(2B); HRMS(ESI)m / z calcd for C 15 B 10 H 19 NOBr - (MH) - 418.16382,found418.16357.

[0107] 7. Preparation of compound 2g

[0108]

[0109] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 4-CF3 phenyl trifluoroborate (75.6 mg, 0.3 mmol). The other methods were the same as those described in the above 1 (the reaction equation is shown above). The product was separated by column chromatography to obtain 2 g 24 mg, with a yield of 59%, which was in line with expectations.

[0110] NMR data: 1H NMR (500 MHz, CDCl3, ppm): δ 7.75-7.74 (d, 2H, J = 10 Hz), 7.63-7.62 (m, 2H), 7.54-7.53 (d, 2H, J = 10 Hz), 7.44-7.41 (m, 1H), 7.37-7.34 (dd, 2H, J = 8 Hz), 5.70 (s, 1H), 3.74 (s, 2H); 13C{1H} NMR (125 MHz) , CDCl3, ppm): δ169.2,134.4,131.2,128.4,127.0,124.7-124.6 (J=3.8Hz),52.3,47.5; 11B{1H}NMR( 160MHz, CDCl3, ppm): δ6.6(1B),-2.2(2B),-4.5(2B),-9.8(2B),-14.4(1B),-17.0(2B); HRMS(ESI)m / z calcd forC 16 H 19 B 10 F3NO - (MH) - 407.23911,found 407.24017.

[0111] 8. Preparation of Compound 2h

[0112]

[0113] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 4-acetylphenyl trifluoroborate (67.8 mg, 0.3 mmol). The other methods were the same as described in the above 1 (the reaction equation is shown above). The product 2h was separated by column chromatography (13 mg). The yield was 33.1%, which was in line with the expectation.

[0114] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ 7.87-7.85 (m, 2H), 7.73-7.72 (m, 2H), 7.63-7.62 (m, 2H), 7.44-7.41 (m, 1H), 7.36-7.33 (m, 2H), 5.71 (s, 1H), 3.74 (s, 2H), 2.56 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3, ppm): δ198.2,169.3,137.2,134.3,131.2,128.4,127.6,127.5,127.0,127.0,52.2,47.5,26.6; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.6(1B),-2.3(2B),-4.5(2B),-9.7(2B),-14.2(1B),-16.9(2B); HRMS(ESI)m / z calcd for C 17 H 24 B 10 NO2 + (M+H) + 382.28047,found 382.28088.

[0115] 9. Preparation of Compound 2i

[0116]

[0117] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 2-methylphenyl trifluoroborate (59.4 mg, 0.3 mmol). The other methods were the same as described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 25 mg of the product 2i with a yield of 71%, which was in line with expectations.

[0118] NMR data: 1HNMR (500 MHz, CDCl3, ppm): δ7.64-7.63 (d, 1H, J = 10 Hz), 7.61-7.59 (m, 2H), 7.42-7.39 (m, 1H), 7.34-7.31 (m, 2H), 7.22-7.19 (m, 1H), 7.14-7.12 (dd, 2H, J = 10 Hz), 5.69 (s, 1H), 3.90 (s, 1H), 3.67 (s, 1H), 2.58 (s, 3H); 13C{1H}N MR (125MHz, CDCl3, ppm): δ169.1,142.2,136.7,135.9,131.1,131.0,128.8,128.3,127.0,125.5,51.8,47.2,23.8; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.6(1B),-3.1(1B),-4.1(1B),-9.6(2B),-14.0(1B),-17.2(4B); HRMS(ESI)m / z calcd for C 16 H 22 B 10 NO - (MH) - 353.26737,found353.26849.

[0119] 10. Preparation of Compound 2j

[0120]

[0121] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 3-methylphenyl trifluoroborate (59.4 mg, 0.3 mmol). The other procedures were the same as those described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 26.5 mg of the product 2j with a yield of 75%, which was in line with expectations.

[0122] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ7.64-7.62 (m, 2H), 7.41-7.39 (m, 3H), 7.35-7.32 (m, 2H), 7.22-7.18 (dd, 1H, J = 12 Hz), 7.15-7.13 (d, 1H, J = 12 Hz), 5.69 (s, 1H), 3.70 (s, 1H), 2.31 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3, ppm): δ7.64-7.62 (m, 2H), 7.41-7.39 (m, 3H), 7.35-7.32 (m, 2H), 7.22-7.18 (dd, 1H, J = 12 Hz), 7.15-7.13 (d, 1H, J = 12 Hz), 5.69 (s, 1H), 3.70 (s, 1H), 2.31 (s, 3H); l3, ppm): δ169.2,137.4,135.9,134.8,131.2,131.0,129.7,128.3,128.0,127.0,52.2,47.4,21.4; 11B{1 H}NMR (160MHz, CDCl3, ppm): δ6.5 (1B), -2.4 (2B), -3.7 (1B), -9.8 (2B), 14.2 (1B), 17.0 (3B); HRMS (ESI) m / z calcdfor C 16 B 10 H 22 NO - (MH) - 352.27101,found 352.27127.

[0123] 11. Preparation of Compound 2k

[0124]

[0125] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 4-methylphenyl trifluoroborate (59.4 mg, 0.3 mmol). The other methods were the same as described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 23 mg of the product 2k with a yield of 65%, which was in line with expectations.

[0126] NMR data: 1HNMR (600 MHz, CDCl3, ppm): δ7.64-7.62 (m, 2H), 7.52-7.50 (d, 2H, J = 12 Hz), 7.43-7.39 (m, 1H), 7.36-7.32 (m, 2H), 7.13-7.11 (d, 2H, J = 12 Hz), 5.69 (s, 1H), 3.70 (s, 1H), 3.67 (s, 1H), 2.31 (s, 3H); 13C{1H}NMR ( 150MHz, CDCl3, ppm): δ169.2,138.9,135.8,134.2,131.0,128.9,128.3,127.1,52.3,47.5,21.3; 11B{1H} NMR (160MHz, CDCl3, ppm): δ6.5 (1B), -2.4 (1B), -3.7 (2B), -9.9 (2B), -14.4 (1B), -17.1 (3B); HRMS (ESI) m / z calcd forC 16 B 10 H 22 NO - (MH) - 352.27101,found 352.27145.

[0127] 12. Preparation of Compound 21

[0128]

[0129] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 4-tert-butylphenyl trifluoroborate (72 mg, 0.3 mmol). The other methods were the same as described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 24 mg of the product 21 with a yield of 61%, which was in line with expectations.

[0130] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ 7.65-7.62 (m, 2H), 7.57-7.55 (d, 2H, J = 12 Hz), 7.43-7.40 (m, 1H), 7.36-7.32 (dd, 4H, J = 12 Hz), 5.70 (s, 1H), 3.69 (s, 2H), 1.29 (s, 9H); 13C{1H} NMR (150 MHz, CDCl3, ppm): δ169.2,151.9,135.9,134.2,134.0,131.0,128.3,127.1,125.0,52.3,47.4,34.6,31.2; 11B{1H}NMR ( 160MHz, CDCl3, ppm): δ6.5(1B),-2.3(1B),-3.6(2B),-9.9(2B),-14.3(1B),-17.2(3B); HRMS(ESI)m / z calcd for C 19 B 10 H 28 NO - (MH) - 394.31796, found 394.31775.

[0131] 13. Preparation of Compound 2m

[0132]

[0133] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 3-methoxyphenyl trifluoroborate (64.2 mg, 0.3 mmol). The other methods were the same as described in the above 1 (the reaction equation is shown above). The product 2m was separated by column chromatography (29.2 mg). The yield was 79%, which was in line with expectations.

[0134] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ7.65-7.63 (m, 2H), 7.43-7.40 (m, 2H), 7.35-7.33 (dd, 2H, J = 6 Hz), 7.24-7.21 (dd, 1H, J = 6 Hz), 7.19-7.18 (m, 2H), 5.71 (s, 1H), 3.75 (s, 3H), 3.70 (s, 2H); 13C{1H} NMR (150 MHz, CDCl3, p pm): δ169.2,159.1,135.8,131.1,129.2,128.3,127.0,126.3,119.5,114.6,55.1,52.3,47.4; 11B{1H}NMR ( 160MHz, CDCl3, ppm): δ6.5(1B),-2.4(1B),-3.9(2B),-9.9(2B),-14.3(1B),-17.3(3B); HRMS(ESI)m / zcalcd for C 16 H 22 B 10 NO2 - (MH) - 369.26229,found 369.26340.

[0135] 14. Preparation of Compound 2n

[0136]

[0137] The potassium phenyl trifluoroborate (55.2 mg, 0.3 mmol) in the above 1 was replaced by potassium 1-naphthylphenyl trifluoroborate (71 mg, 0.3 mmol). The other methods were the same as described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 29.6 mg of the product 2n with a yield of 75.6%, which was in line with expectations.

[0138] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ 8.75-8.73 (d, 1H, J = 6 Hz), 7.95 (m, 1H), 7.85-7.83 (dd, 2H, J = 6 Hz), 7.52-7.49 (m, 3H), 7.48-7.45 (dd, 1H, J = 6 Hz), 7.43-7.40 (m, 1H), 7.35-7.33 (m, 1H), 7.26-7.23 (m, 2H), 5.70 (s, 1H), 3.93 (s, 1H), 3.71 (s, 1H); 13C{1H} NMR (150MHz, CDCl3, ppm): δ169.2,136.1,135.8,133.8,131.0,130.2,130.2,129.2,128.2,127.1,127.0,127.0,126.2,125.3,125. 2,52.5,47.3; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.8(1B),-2.7(2B),-4.0(2B),-9.5(2B),-13.6(1B),-16.9(2B); HRMS(ESI)m / z calcd forC 19 H 22 B 10 NO - (MH) - 389.26737,found 389.26923.

[0139] 15. Preparation of compound 2o

[0140]

[0141] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with 4-methyl-B(9)-amide-o-carborane 1a (27.7 mg, 0.1 mmol). The other procedures were the same as those described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 19.1 mg of the product 2o in a yield of 54%, which was in line with the expected value.

[0142] NMR data: 1HNMR (600 MHz, CDCl3, ppm): δ7.62-7.61 (d, 2H, J = 6 Hz), 7.53-7.51 (d, 2H, J = 6 Hz), 7.32-7.28 (m, 3H), 7.14-7.12 (d, 2H, J = 6 Hz), 5.67 (s, 1H), 3.70 (s, 2H), 2.34 (s, 3H); 13C{1H}NMR (150 MHz, CDCl3, p pm): δ169.3,141.4,134.1,132.9,129.0,128.9,128.0,127.9,127.0,52.3,47.4,21.3; 11B{1H}NMR ( 160MHz, CDCl3, ppm): δ6.5(1B),-2.4(1B),-3.8(2B),-9.8(2B),-14.4(1B),-17.2(3B); HRMS(ESI)m / z calcd for C 16 H 22 B 10 NO - (MH) - 353.26737,found 353.26849.

[0143] 16 Preparation of compound 2p

[0144]

[0145] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with 3-methyl-B(9)-amide-o-carborane 1a (27.7 mg, 0.1 mmol). The other methods were the same as those described in the above 1 (the reaction equation is shown above). Under argon atmosphere, 3-methyl-B(9)-amide-o-carborane 1a (27.7 mg, 0.1 mmol), dry THF (1 mL), potassium phenyltrifluoroborate (55.2 mg, 0.3 mmol), palladium tetraacetonitrile tetrafluoroborate (4.5 mg, 10 mol%), silver oxide (46 mg, 0.2 mmol), and copper acetate (20 mg, 0.1 mmol) were added sequentially to a dry 10 mL round-bottom flask. The round-bottom flask was placed in an oil bath at 50° C. for 24 h, and the progress of the reaction was monitored by TLC. After the reaction, the system was filtered with filter paper, concentrated under reduced pressure, and then purified by column chromatography using petroleum ether / ethyl acetate = 4:1 to 3:1 as eluent. The product 2p19.1 mg was obtained by column chromatography with a yield of 54%, which was in line with expectations.

[0146] NMR data: 1HNMR (600MHz, CDCl3, ppm): δ7.63-7.62 (d, 2H, J=6Hz), 7.45 (s, 1H), 7.40-7.39 (m, 1H), 7.33-7.30 (m, 3H), 7.22-7.21 (m, 2H), 5.68 (s, 1H), 3.70 (s, 2H), 2.32 (s, 3H), 13C{1H}NMR (150MHz, CDCl3, ppm): δ169.5,138.1,135.7,134.2,131.8,128.9,128.2,128.0,127.9,124.0,52.3,47.5,21.3; 11B{1H}NMR ( 160MHz, CDCl3, ppm): δ6.5(1B),-2.4(2B),-3.7(2B),-10.1(2B),-14.6(1B),-17.8(2B); HRMS(ESI)m / z calcd for C 16 H 22 B 10 NO - (MH) - 353.26737,found 353.26855.

[0147] 17. Preparation of Compound 2q

[0148]

[0149] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with 4-methoxy-B(9)-amide-o-carborane 1a (29.3 mg, 0.1 mmol). The other methods were the same as those described in the above 1 (the reaction equation is shown above). The product 2q was separated by column chromatography to obtain 19.2 mg of the product with a yield of 52%, which was in line with the expected value.

[0150] NMR data: 1HNMR (600MHz, CDCl3, ppm): δ7.62-7.59 (m, 4H), 7.33-7.30 (m, 3H), 6.83-6.82 (m, 2H), 5.62 (s, 1H), 3.80 (s, 3H), 3.69 (s, 2H), 13C{1H}NMR (150MHz, CDCl3, ppm): δ168.7, 161.9,134.2,128.9,128.8,128.0,113.5,55.3,52.2,47.3; 11B{1H}NMR (160MHz, CDCl3 ,ppm): δ6.6(1B),-2.3(2B),-3.8(2B),-9.8(2B),-14.2(1B),-17.0(2B); HRMS(ESI)m / z calcd for C 16 H 22 B 10 NO2 - (MH) - 369.26229,found 369.26358.

[0151] 18. Preparation of Compound 2r

[0152]

[0153] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with 2-methoxy-B(9)-amide-o-carborane 1a (29.3 mg, 0.1 mmol). The other methods were the same as those described in the above 1 (the reaction equation is shown above). The product r was separated by column chromatography to obtain 14.4 mg of the product with a yield of 39%, which was in line with the expectation.

[0154] NMR data: 1HNMR (600MHz, CDCl3, ppm): δ7.62-7.59 (m, 4H), 7.33-7.28 (m, 3H), 6.83-6.82 (m, 2H), 5.62 (s, 1H), 3.80 (s, 3H), 3.69 (s, 2H); 13C{1H}NMR (150MHz, CDCl3, ppm): δ166.9, 157.5, 134 .2,133.0,132.5,132.4,128.8,128.0,121.1,111.4,55.6,51.9,47.3; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.8(1B),-2.5(2B),-4.2(2B),-9.6(2B),-14.0(1B),-16.8(2B); HRMS(ESI)m / z calcd for C 16H 22 B 10 NO2 - (MH) - 369.26229,found369.26352.

[0155] 19. Preparation of Compound 2s

[0156]

[0157] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with 4-tert-butyl-B(9)-amide-o-carborane 1a (31.9 mg, 0.1 mmol). The other methods were the same as described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 20.1 mg of the product 2s with a yield of 51%, which was in line with expectations.

[0158] NMR data: 1H NMR (600 MHz, CDCl 3 , ppm): δ 7.63-7.61 (d, 2H, J = 6 Hz), 7.57-7.56 (d, 2H, J = 6 Hz), 7.36-7.35 (m, 1H), 7.34 (s, 1H), 7.33-7.31 (m, 2H), 7.30-7.29 (m, 1H), 5.68 (s, 1H), 3.70 (s, 2H); 13C{1H} NMR (150 MHz, CDCl 3 , ppm): δ169.1,154.5,134.1,133.5,132.9,128.9,128.1,128.0,126.9,125.4,125.2,52.3,47.4,34.8,31.1; 11B{1 H}NMR (160MHz, CDCl3, ppm): δ6.6(1B),-2.4(1B),-3.8(2B),-9.8(2B),-14.3(1B),-17.1(3B); HRMS(ESI)m / z calcd for C 19 H 28 B 10 NO - (MH) - 395.31432,found 395.31573.

[0159] 20. Preparation of Compound 2t

[0160]

[0161] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with B(9)-cyclopropylamide-o-carborane 1a (22.7 mg, 0.1 mmol). The other procedures were the same as those described in the above 1 (the reaction equation is shown above). The product 2t was separated by column chromatography to obtain 20.6 mg of the product 2t in a yield of 68%, which was in line with the expected value.

[0162] NMR data: 1HNMR (600 MHz, CDCl3, ppm): δ7.60-7.58 (m, 2H), 7.36-7.32 (m, 3H), 5.19 (s, 1H), 3.66 (s, 1H), 3.63 (s, 1H), 1.19-1.17 (m, 1H), 0.91-0.88 (m, 1H), 0.84-0.83 (m, 1H), 0.64-0.59 (m, 2H); 13C{1H} NMR (150MHz, CDCl3, ppm): δ175.6,134.3,128.9,128.0,52.2,47.1,16.0,7.5,7.3; 11B{1H}NMR(16 0MHz, CDCl3, ppm): δ6.3(1B),-2.5(1B),-3.9(2B),-9.9(2B),-14.4(2B),-17.2(2B); HRMS(ESI)m / z calcd for C 12 H 20 B 10 NO - (MH) - 302.25536,found 302.25620.

[0163] 21. Preparation of Compound 2u

[0164]

[0165] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with B(9)-benzylamide-o-carborane 1a (22.7 mg, 0.1 mmol). The other methods were the same as those described in the above 1 (the reaction equation is shown above). The product 2u was separated by column chromatography to obtain 18.7 mg of the product 2u. The yield was 53%, which was in line with the expectation.

[0166] NMR data: 1HNMR (600 MHz, CDCl3, ppm): δ7.47-7.46 (d, 2H, J = 6 Hz), 7.37-7.34 (dd, 1H, J = 6 Hz), 7.29-7.27 (dd, 2H, J = 6 Hz), 7.20-7.19 (m, 3H), 7.00-6.99 (m, 2H), 4.93 (s, 1H), 3.65 (s, 1H), 3.62 (s, 1H), 3.42 (s, 2H); 13C{1H}N MR (150MHz, CDCl3, ppm): δ173.2,135.4,134.0,129.2,128.8,128.7,128.0,126.9,52.1,47.5,45.1; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.2(1B),-2.7(1B),-3.9(2B),-10.0(2B),-14.4(1B),-17.0(3B); HRMS(ESI)m / z calcd for C 16 H 22 B 10 NO - (MH) - 353.26737,found 353.26840.

[0167] 22. Preparation of compound 2v

[0168]

[0169] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with B(9)-benzylnaphthaleneamide-o-carborane 1a (22.7 mg, 0.1 mmol). The other procedures were the same as those described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 23.4 mg of the product 2v with a yield of 58%, which was in line with expectations.

[0170] NMR data: 1H NMR (500 MHz, CDCl3, ppm): δ 7.82-7.80 (d, 1H, J = 10 Hz), 7.73-7.71 (d, 2H, J = 10 Hz), 7.46-7.43 (m, 1H,), 7.37-7.33 (m, 1H), 7.32-7.29 (m, 4H), 7.18-7.15 (m, 3H), 4.92 (s, 1H), 3.86 (m, 2H), 3.59 (s, 1H), 3.55 (s, 1H); 13C{1H} NMR (125 M Hz, CDCl3, ppm): δ168.0,139.2,134.1,133.4,132.9,132.6,129.1,128.1,127.4,125.4,125.4,124.8,122.6,52.4,47 .9; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.3(1B),-2.4(2B),-3.7(1B),-9.9(2B),-14.4(1B),-17.1(3B); HRMS(ESI)m / z calcd for C 20 H 26 B 10 NO + (M+H) + 406.29395,found 406.29556.

[0171] 23. Preparation of Compound 2w

[0172]

[0173] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with 2-fluoro B(9)-amide-o-carborane 1a (28.1 mg, 0.1 mmol). The other methods were the same as those described in the above 1 (the reaction equation is shown above). The product 2w was separated by column chromatography to obtain 17.9 mg of the product 2w with a yield of 50%, which was in line with the expectation.

[0174] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ 8.00-7.97 (m, 1H), 7.62-7.61 (m, 2H), 7.37-7.36 (m, 1H), 7.33-7.29 (m, 3H), 7.18-7.15 (m, 1H), 7.01-6.97 (m, 1H), 6.27-6.25 (d, 1H, J = 12 Hz), 3.71 (s, 2H); 13C{1H} NMR (150 MHz, CDCl3, ppm): 165.0-165.0 (J = 3 Hz) ,161.4,159.7,134.0,132.9-132.8(J=9Hz),132.2-132.2(J=5Hz),128.9,128.0,124.5,124.5,115.9-115.8(J=24Hz),52. 1,47.6; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.4(1B),-2.4(2B),-3.9(2B),-9.8(2B),-14.2(1B),-17.1(3B); HRMS(ESI)m / z calcd forC 15 H 19 B 10 FNO - (MH) - 357.24230,found 357.24350.

[0175] 24. Preparation of Compound 2x

[0176]

[0177] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced by 3-fluoro B(9)-amide-o-carborane 1a (28.1 mg, 0.1 mmol). Other methods were the same as described in the above 1. Column chromatography was used to obtain the product 2 x 16.8 mg with a yield of 47%, which was in line with expectations.

[0178] NMR data: 1H NMR (600 MHz, CDCl3, ppm): δ 7.62-7.61 (m, 2H), 7.35-7.35 (m, 1H), 7.34-7.33 (m, 2H), 7.32-7.31 (m, 2H), 7.30-7.29 (m, 1H), 7.12-7.09 (m, 1H), 5.63 (s, 1H), 3.73 (s, 2H); 13C{1H} NMR (150 MHz, CDCl3, ppm): 168.0, 163.4-161.8 (J = 246 Hz) ,134.1,129.9,129.9-129.0(J=8Hz),128.1,122.4-122.4(J=3Hz),118.1-118.0(J=21Hz),114.5-114.4(J=23Hz),52.3, 47.1; 11B{1H}NMR (160MHz, CDCl3, ppm): δ6.4(1B),-2.3(1B),-3.7(2B),-9.8(2B),-14.3(1B),-16.9(3B); HRMS(ESI)m / z calcd for C 15 H 19 B 10 FNO - (MH) - 357.24230,found 357.24356.

[0179] 25. Preparation of compound 2y:

[0180]

[0181] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with 4-fluoro B(9)-amide-o-carborane 1a (29.8 mg, 0.1 mmol). The other procedures were the same as those described in the above 1 (the reaction equation is shown above). Column chromatography was performed to obtain 18.3 mg of the product 2y in a yield of 49%, which was in line with the expected value.

[0182] NMR data: 1HNMR (600MHz, CDCl3, ppm): δ7.61-7.60 (m, 2H), 7.55-7.54 (m, 2H), 7.35-7.32 (m, 1H), 7.31-7.29 (m, 4H), 5.62 (s, 1H), 3.72 (s, 2H); 13C{1H}NMR (150MHz, CDCl3, ppm): 168.2 ,137.3,134.2,134.1,129.0,128.5,128.5,128.1,52.3,47.7; 11B{1H}NMR (160MHz, CDCl 3, ppm): δ6.4(1B),-2.4(1B),-3.7(2B),-9.8(2B),-14.3(1B),-17.0(3B); HRMS(ESI)m / z calcd for C 15 H 19 B 10 ClNO - (MH) - 373.21275,found 373.21371.

[0183] 26. Preparation of compound 2z:

[0184]

[0185] The B(9)-amide-o-carborane 1a (26.3 mg, 0.1 mmol) in the above 1 was replaced with 4-trifluoromethyl-B(9)-amide-o-carborane 1a (34.3 mg, 0.1 mmol). The other methods were the same as those described in the above 1 (the reaction equation is shown above). The product 2z (16.3 mg) was separated by column chromatography. The yield was 39%, which was in line with the expectation.

[0186] NMR data: 1H NMR (500 MHz, CDCl3, ppm): δ 7.70 - 7.69 (d, 2H, J = 10 Hz), 7.62 - 7.58 (m, 4H), 7.34 - 7.29 (m, 3H), 5.67 (s, 1H), 3.74 (s, 2H); 13C{1H} NMR (125 MHz, CDCl3, ppm): 173.0, 128.7 - 128.5 (J = 25 Hz), 128.0 - 128.0 (J = 8 Hz), 127.9, 126.5, 125.8, 125.4, 123.8, 52.0, 47.4, 43.1; 11B{1H} NMR (160 MHz, CDCl3, ppm): δ 6.2 (1B), -2.9 (1B), -4.2 (1B), -10.1 (2B), -14.7 (1B), -17.7 (4B); HRMS (ESI) m / z calcd for C 16 H 19 B 10 F3NO - (M - H) - 407.23856, found 407.24042。

Claims

1. A method for preparing a B(4)-aryl-B(9)-amide-o-carborane derivative, characterized in that: The preparation method of the derivative is represented by the following general formula (2): Using 9-amide-o-carborane derivatives as raw materials, in an argon atmosphere, with Pd(MeCN)4(BF4)2 as catalyst, Cu(OAc)2 and Ag2O as oxidants, the reaction was carried out in tetrahydrofuran, and potassium aryl trifluoroborate was used to undergo selective oxidative coupling with B(4)-H to prepare B(4)-aryl-B(9)-amide-o-carborane derivatives; Wherein, R1 is one of phenyl, substituted phenyl, benzyl, benzylnaphthalene or cyclopropyl; The R2 is one of phenyl, substituted phenyl or naphthyl.

2. The method for preparing a B(4)-aryl-B(9)-amide-o-carborane derivative according to claim 1, wherein: The substituent of the substituted phenyl group is one of halogen, methyl, methoxy, trifluoromethyl, tert-butyl and acetyl.

3. The B(4)-aryl-B(9)-amide-o-carborane derivative according to claim 2, characterized in that: The substituent of the substituted phenyl group in R1 is one of halogen, methyl, methoxy, trifluoromethyl, and tert-butyl; the substituent of the substituted phenyl group in R2 is one of halogen, methyl, methoxy, trifluoromethyl, tert-butyl, and acetyl.

4. The preparation method according to claim 1, wherein: The preparation method of the 9-amide-o-carborane derivative is as follows: (1) reacting an o-carborane derivative with dichloromethane, I2 and AlCl3 catalyst to obtain a 9-Io-carborane derivative; (2) 9-Io-Carborane derivatives react with R1 formamide, Pd2(dba)3, K3PO4, DavePhos and toluene to obtain 9-amide-o-Carborane derivatives.

5. The preparation method according to claim 4, wherein The method further comprises: Filtration, concentration, and separation: After the reaction is completed, the system temperature is cooled to room temperature and filtered through a short silica gel column using ethyl acetate as the eluent. The filtrate is concentrated under reduced pressure and purified by column chromatography using petroleum ether / ethyl acetate = 5:1 as the eluent to obtain a B(4)-aryl-B(9)-amide-o-carborane derivative.

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