2-phenyl-4-pinanoylboronyl-2,1-borazaphenanthrene, 2-phenyl-4-pyrimidinyl-2,1-borazaphenanthrene compounds and methods for their preparation

Abstract

The application discloses a 2-phenyl-4-pinacol boron-based-2,1-boronazanaphthalene, a 2-phenyl-4-pyrimidyl-2,1-boronazanaphthalene compound and a preparation method thereof, and belongs to the technical field of organic synthesis chemistry. The method is based on a copper-catalyzed selective dehydrogenation boronation reaction strategy, 2-phenyl-2,1-boronazanaphthalene and pinacol diboron ester are used as raw materials, CuCl is used as a catalyst, 4,5-bis(diphenylphosphino)-9,9-dimethyloxyanthracene is used as a ligand, 2-adamantanone is used as an additive, p-xylene is used as a solvent, and 2-phenyl-4-pinacol boron-based-2,1-boronazanaphthalene is efficiently obtained. The 2-phenyl-4-pinacol boron-based-2,1-boronazanaphthalene compound synthesized by the application can be used as a key intermediate, is efficiently converted through a C-B bond, and is convenient for synthesizing a 2-phenyl-4-pyrimidyl-2,1-boronazanaphthalene compound, thereby providing a new way for functional modification of boronazacyclic compounds.

Description

Technical Field

[0001] This invention belongs to the field of organic synthetic chemistry technology, specifically relating to a 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene compound, a 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound, and its preparation method. Background Technology

[0002] In recent years, research on boron-nitrogen heterocyclic compounds has attracted increasing attention. Among them, 2,1-boron-nitrogen heterocycles, as a unique class of isosteres with electrons of benzene, possess many excellent physical and chemical properties and are widely found in drugs, bioactive molecules, optoelectronic materials, and novel ligands. For example, the NH bond in 2,1-boron-nitrogen heterocycles has donor properties and can bind to proteins, making it valuable in drug development. 2,1-boron-nitrogen heterocycle derivatives can be used to prepare materials with special optical properties. The synthesis of 1,2-boron-nitrogen heterocycles by simulating biomimetic C=C bonds using isosteric BN bonds has become a research hotspot in the chemical community. Therefore, developing efficient methods for synthesizing novel boron-nitrogen heterocyclic compounds is essential.

[0003] While some progress has been made in the synthesis of boron-nitrogen heterocyclic compounds, previous studies have mostly employed noble metal palladium and iridium catalytic systems to synthesize diverse boron-nitrogen heterocyclic compounds (Davies, GHM; Jouffroy, M.; Sherafat, F.; Saeednia, B.; Howshall, C.; Molander, GAJ Org. Chem. 2017, 82, 8072-8084. Choi, S.; Dong, GJ Am. Chem. Soc. 2024, 146, 9512-9518.). These catalysts are relatively expensive and can easily cause environmental pollution. Furthermore, methods involving reaction sites at the C4 position are relatively rare (Zhuang, F.; Han, J.; Tang, S.; Yang, J.; Chen, Q.; Wang, J.; Pei, J. Organometallics 2017, 36, 14, 2479-2482). This invention utilizes a copper-catalyzed dehydrogenation-boronization strategy to regioselectively introduce a borate ester group at the C4 position, synthesizing a novel class of boron-nitrogen heterocyclic compounds, which has not been previously reported. Furthermore, 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, as a special type of 2,1-boron-nitrogen heterocycle, exhibits greater versatility due to the relatively reactive borate ester group in its molecule, facilitating functional group transformation and providing more possibilities for subsequent structural modification and derivatization. Compared to the synthetic methods of other boron-nitrogen heterocyclic compounds, the method described in this invention is simpler and less expensive, and is expected to provide important guidance and reference value for the synthetic research of structurally diverse boron-nitrogen heterocyclic compounds. Summary of the Invention

[0004] The purpose of this invention is to provide a compound of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene and 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene and its preparation method.

[0005] The following techniques are used to achieve the objectives of this invention:

[0006] A 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, the structural formula of which is shown below: .

[0007] A method for preparing 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene includes the following steps:

[0008] Step 1: Under an argon protective atmosphere, add the catalyst CuCl, ligand 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (Xantphos), base lithium tert-butoxide (LiOtBu), and solvent p-xylene sequentially to a 25 mL reaction tube equipped with a stir bar, and react at 25±3 °C for 10 min to 15 min to generate a light white catalyst pre-stirred solution;

[0009] Step 2: Under an argon protective atmosphere, pinacol ester (B2pin2) of borate was added to the pre-stirred catalyst solution and reacted at 25±3 °C for 10 min to 15 min. Subsequently, 2-phenyl-2,1-borazanaphthalene and 2-adamantanone were added sequentially. The reaction tube was sealed and reacted at 100±3 °C for 12 h to 72 h. The crude product obtained from the reaction was purified by silica gel column chromatography to obtain 2-phenyl-4-pinacol boron-2,1-borazanaphthalene.

[0010] In the above technical solution: 2-phenyl-2,1-boronazonaphthalene and B2pin2 are used as reactants, CuCl is used as catalyst, 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (Xantphos) is used as ligand, 2-adamantanone is used as additive, lithium tert-butoxide (LiOtBu) is used as base, and p-xylene is used as solvent. 2-Phenylene-4-pinacolboryl-2,1-boronazonaphthalene is synthesized efficiently through a copper-catalyzed selective dehydrogenation boronization strategy.

[0011] Furthermore, in a method for preparing 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, the molar amount of the catalyst CuCl is 15% of 2-phenyl-2,1-borazonaphthalene, the molar amount of the ligand Xantphos is 20% of 2-phenyl-2,1-borazonaphthalene, and the molar amount of the base LiOtBu is 30% of 2-phenyl-2,1-borazonaphthalene.

[0012] Further: In a method for preparing 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, the molar ratio of 2-phenyl-2,1-borazonaphthalene, pinacolboryl diborate (B2pin2), and 2-adamantanone is 1.0 : 3.0 : 2.5, and the concentration of 2-phenyl-2,1-borazonaphthalene in p-xylene is 0.1 M.

[0013] Further: In the preparation method of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, the eluent used in the column chromatography is petroleum ether / ethyl acetate with a volume ratio of 45:1.

[0014] Further: In the preparation method of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, the reaction temperature after sealing the reaction tube is 100±3 ℃ and the reaction time is 12 h.

[0015] Furthermore: In a method for preparing 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, the ligand 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (Xantphos) has the following structural formula: .

[0016] A 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound, the structural formula of which is shown below: .

[0017] A method for preparing a 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound includes the following steps:

[0018] Step 1: Under an argon protective atmosphere, add the catalyst CuCl, ligand 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (Xantphos), base lithium tert-butoxide (LiOtBu), and solvent p-xylene sequentially to a 25 mL reaction tube equipped with a stir bar, and react at 25±3 °C for 10 min to 15 min to generate a light white catalyst pre-stirred solution;

[0019] Step 2: Under an argon protective atmosphere, pinacol ester (B2pin2) of borate was added to the pre-stirred catalyst solution and reacted at 25±3 °C for 10 min to 15 min. Subsequently, 2-phenyl-2,1-borazanaphthalene and 2-adamantanone were added sequentially. The reaction tube was sealed and reacted at 100±3 °C for 12 h to 72 h. The crude product obtained from the reaction was purified by silica gel column chromatography to obtain 2-phenyl-4-pinacol boron-2,1-borazanaphthalene.

[0020] Step 3: Under an argon protective atmosphere, a mixture of tert-butanol (tBuOH) and deionized water (H2O) was added to a 25 mL reaction tube containing 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, catalyst chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (Xphos-Pd-G2), 5-iodopyrimidine, K2CO3, and a stir bar. The reaction tube was sealed and reacted at 50±3 °C for 12 h ~ 18 h. After the reaction was completed, the mixture was extracted with ethyl acetate, the resulting organic phase was washed with saturated sodium chloride solution, dried with anhydrous Na2SO4, filtered, concentrated under reduced pressure to obtain the crude product, and then subjected to column chromatography to obtain 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene molecules.

[0021] In the above technical solution: 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene is further synthesized and transformed to obtain 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene. The overall synthetic route is shown below: .

[0022] Further: The catalyst used in the preparation method of a 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound, chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (Xphos-Pd-G2), has the CAS number 1310584-14-5 and the structural formula: .

[0023] Further: In a method for preparing a 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound, the molar amount of the catalyst Xphos-Pd-G2 is 2% of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene.

[0024] Further: In a method for preparing a 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound, the molar ratio of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, 5-iodopyrimidine, and K2CO3 is 1.0 : 1.1 : 3.0.

[0025] Further: In a method for preparing a 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound, the eluent used in column chromatography is petroleum ether / ethyl acetate with a volume ratio of 6:1, and the concentration of the 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene in the tert-butanol / deionized water mixed solvent is 0.1 M.

[0026] Further: In a method for preparing a 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound, a mixed solvent of tert-butanol (tBuOH) and deionized water (H2O) reacts with 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, the catalyst chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (Xphos-Pd-G2), 5-iodopyrimidine, and K2CO3 at a temperature of 50±3 °C for 12 h.

[0027] Compared with the prior art, the present invention has the following advantages:

[0028] (1) Using stable and readily available 2-phenyl-2,1-borazonaphthalene and pinacol ester (B2pin2) as raw materials, the present invention synthesized 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene (compound 3) for the first time under simple and easy reaction conditions. Further synthesis and transformation of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene (compound 3) were carried out to obtain 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene (compound 5) for the first time.

[0029] (2) This invention utilizes a copper-catalyzed selective dehydrogenation and boronization functionalization strategy to induce the 2-phenyl-2,1-borazonaphthalene compound to undergo a boronization reaction at the C4 position, thus obtaining the 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene compound (compound 3) for the first time. The method is simple to operate, environmentally friendly, and low in cost. The raw materials used are stable and readily available, and the reaction regioselectivity is good, with a high yield. This provides a new approach for the synthesis of novel boron-nitrogen heterocyclic compounds.

[0030] (3) The 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene compound (compound 3) synthesized in this invention can be used as a key intermediate to efficiently and conveniently synthesize the 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound (compound 5) through CB bond conversion, providing a new approach for the functionalization modification of boron-nitrogen heterocyclic compounds. Attached Figure Description

[0031] Figure 1 The synthetic route diagram for 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene (compound 5) obtained in Example 1 is shown.

[0032] Figure 2 The 1H NMR spectrum of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene (compound 3) prepared in Example 1;

[0033] Figure 3 The carbon spectrum of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene (compound 3) prepared in Example 1;

[0034] Figure 4 The boron spectrum of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene (compound 3) prepared in Example 1;

[0035] Figure 5 The 1H NMR spectrum of 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene (compound 5) prepared in Example 1;

[0036] Figure 6 The carbon spectrum of 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene (compound 5) prepared in Example 1;

[0037] Figure 7The boron spectrum of 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene (compound 5) prepared in Example 1 is shown. Detailed Implementation

[0038] The present invention will be further described in detail below with reference to embodiments and accompanying drawings.

[0039] In the following examples, 2-phenyl-2,1-boronazonaphthalene (compound 1) was prepared according to references (Dewar, MJS; Dietz, RJ Chem. Soc. 1959, 2728-2730; Huang, HN; Pan, ZX; Cui, CM Chem. Commun. 2016, 52, 4227-4230.), pinacol diboronate (B2pin2) (compound 2), catalyst CuCl, ligand 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (Xantphos), additive 2-adamantanone, base lithium tert-butoxide (LiOtBu), potassium carbonate (K2CO3), Xphos-Pd-G2, 5-iodopyrimidine (compound 4), etc., are all commercially available. Example

[0040] A method for preparing 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene and 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compounds:

[0041] Step 1: The reaction was carried out in a double-tube system. Under an argon protective atmosphere, the catalyst CuCl (1.5 mg, 15 mol%), ligand Xantphos (12 mg, 20 mol%), base lithium tert-butoxide LiOtBu (2.4 mg, 30 mol%), and reaction solvent p-xylene (1.0 mL) were added to a 25 mL reaction tube equipped with a stir bar. The reaction was carried out at 25 °C for 10 min to generate a light white catalyst pre-stirred solution.

[0042] Step 2: Under an argon protective atmosphere, pinacol ester (B2pin2) (compound 2) (76.2 mg, 3.0 eq.) was added to the pre-stirred catalyst solution, and the reaction was carried out at 25 °C for 10 min. The reaction system was milky white. Subsequently, 2-phenyl-2,1-borazonaphthalene (compound 1) (21 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) were added sequentially, and the reaction system turned yellowish-brown. Finally, the reaction tube was sealed and the reaction was carried out at 100 °C for 12 h. During the reaction, the reaction system gradually turned black. After the reaction was completed, the crude product was purified by silica gel column chromatography to obtain 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene (compound 3) with a yield of 86%.

[0043] 1 H NMR (500 MHz, Chloroform- d ) δ 8.46 (d, J = 8.0 Hz, 1H), 8.15 (s,1H), 8.03 (s, 1H), 7.91 (d, J = 6.0 Hz, 2H), 7.42 – 7.34 (m, 4H), 7.22 – 7.18(m, 2H), 1.37 (s, 12H);

[0044] 13 C NMR (126 MHz, Chloroform- d ) δ 140.89, 139.72, 138.02, 132.89,129.96, 129.68, 128.22, 128.09, 127.74, 121.29, 118.72, 84.13, 25.02;

[0045] 11 B NMR (160 MHz, Chloroform- d ) δ 31.23;

[0046] HRMS(ESI) m / z: calculated for [C 20 H 23 B2NO2 + Na] + 354.1807, found354.1812.

[0047] Step 3: The reaction was carried out in a double-tube system. Under an argon protective atmosphere, 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene (compound 3) (33.2 mg, 1.0 eq.), Xphos-Pd-G2 (1.6 mg, 2 mol%), 5-iodopyrimidine (compound 4) (22.7 mg, 1.1 eq.), K2CO3 (41.5 mg, 3.0 eq.), tert-butanol (0.5 mL), and deionized water (0.5 mL) were added to a 25 mL reaction tube equipped with a stir bar. The reaction system was brown. The reaction tube was sealed and reacted at 50±3℃ for 12 h. After the reaction was completed, the mixture was extracted three times with ethyl acetate (EA). The obtained organic phase was washed three times with saturated sodium chloride solution, dried with anhydrous Na2SO4, filtered, and the solvent was evaporated to obtain the crude product. The crude product was then subjected to column chromatography to obtain 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene (compound 5) with a yield of 55%.

[0048] The synthetic route for 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene (compound 5) is as follows: .

[0049] 1 H NMR (500 MHz, Chloroform- d ) δ 9.32 (s, 1H), 8.88 (s, 2H), 8.32 (s,1H), 7.94 – 7.92 (m, 2H), 7.54 – 7.45 (m, 6H), 7.20 – 7.16 (m, 2H);

[0050] 13 C NMR (126 MHz, Chloroform- d ) 158.03, 156.64, 149.31, 140.89, 136.31, 132.85, 131.75, 130.23, 129.38, 128.53, 127.17, 124.02, 121.82, 119.27;

[0051] 11 B NMR (160 MHz, Chloroform- d ) δ 33.71;

[0052] HRMS(ESI) m / z: calculated for [C 18 H 14 BN3 + H] +284.1354. found284.1362.

[0053] Comparative Example 1:

[0054] Comparative Example 1 is essentially the same as Step 1 and Step 2 of Example 1, except that (Compound 1) is replaced with 2-phenyl-3-bromo-2,1-borazonaphthalene (Compound 6). The structural formula of 2-phenyl-3-bromo-2,1-borazonaphthalene (Compound 6) is as follows: .

[0055] The specific steps are as follows:

[0056] Step 1: The reaction was carried out in a double-tube system. Under an argon protective atmosphere, the catalyst CuCl (1.5 mg, 15 mol%), ligand Xantphos (12 mg, 20 mol%), base lithium tert-butoxide LiOtBu (2.4 mg, 30 mol%), and reaction solvent p-xylene (1.0 mL) were added to a 25 mL reaction tube equipped with a stir bar. The reaction was carried out at 25 °C for 10 min to generate a catalyst pre-stirred solution.

[0057] Step 2: Under an argon protective atmosphere, pinacol diboronate (B2pin2) (compound 2) (76.2 mg, 3.0 eq.) was added to the pre-stirred catalyst solution, and the reaction was carried out at 25 °C for 10 min. Subsequently, 2-phenyl-3-bromo-2,1-borazanaphthalene (compound 6) (28.5 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) were added sequentially. Finally, the reaction tube was sealed and reacted at 100 °C for 12 h. Thin-layer chromatography (TLC) analysis showed that no obvious spots of the target product 2-phenyl-3-bromo-4-pinacol boron-2,1-borazanaphthalene were observed in the reaction system, and the main spot positions were consistent with those of the starting substrate compound 6.

[0058] Comparative Example 2:

[0059] Comparative Example 2 is basically the same as Step 1 and Step 2 of Example 1, the only difference being that the reaction solvent in Step 1 is mesitylene. The specific steps are as follows:

[0060] Step 1: The reaction was carried out in a double-tube system. Under an argon protective atmosphere, the catalyst CuCl (1.5 mg, 15 mol%), ligand Xantphos (12 mg, 20 mol%), base lithium tert-butoxide LiOtBu (2.4 mg, 30 mol%), and reaction solvent tricresylbenzene (1.0 mL) were added to a 25 mL reaction tube equipped with a stir bar. The reaction was carried out at 25 °C for 10 min to generate a catalyst pre-stirred solution.

[0061] Step 2: Under an argon protective atmosphere, pinacol diboronate (B2pin2) (compound 2) (76.2 mg, 3.0 eq.) was added to the pre-stirred catalyst solution, and the reaction was carried out at 25 °C for 10 min. Subsequently, 2-phenyl-2,1-borazanaphthalene (compound 1) (21 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) were added sequentially. Finally, the reaction tube was sealed and reacted at 100 °C for 12 h. After the reaction was completed, the crude product was purified by silica gel column chromatography to obtain 2-phenyl-4-pinacolboron-2,1-borazanaphthalene (compound 3) in 61% yield.

[0062] Comparative Example 3:

[0063] Comparative Example 3 is essentially the same as Step 1 and Step 2 of Example 1, except for the molar ratio of 2-phenyl-2,1-borazonaphthalene (Compound 1), pinacol diboronate (B2pin2) (Compound 2), and 2-adamantanone in Step 2. The specific steps are as follows:

[0064] Step 1: The reaction was carried out in a double-tube system. Under an argon protective atmosphere, the catalyst CuCl (1.5 mg, 15 mol%), ligand Xantphos (12 mg, 20 mol%), base lithium tert-butoxide LiOtBu (2.4 mg, 30 mol%), and reaction solvent p-xylene (1.0 mL) were added to a 25 mL reaction tube equipped with a stir bar. The reaction was carried out at 25 °C for 10 min to generate a catalyst pre-stirred solution.

[0065] Step 2: Under an argon protective atmosphere, pinacol diboronate (B2pin2) (compound 2) (50.8 mg, 2.0 eq.) was added to the pre-stirred catalyst solution, and the reaction was carried out at 25 °C for 10 min. Subsequently, 2-phenyl-2,1-borazanaphthalene (compound 1) (21 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) were added sequentially. Finally, the reaction tube was sealed and reacted at 100 °C for 12 h. After the reaction was completed, the crude product was purified by silica gel column chromatography to obtain 2-phenyl-4-pinacolboron-2,1-borazanaphthalene (compound 3) in 65% yield.

[0066] Comparative Example 4:

[0067] Comparative Example 4 is basically the same as Step 1 and Step 2 of Example 1, except that lithium tert-butoxide (LiOtBu) in Step 1 is replaced with potassium tert-butoxide (KOtBu). The specific steps are as follows:

[0068] Step 1: The reaction was carried out in a double-tube system. Under an argon protective atmosphere, the catalyst CuCl (1.5 mg, 15 mol%), ligand Xantphos (12 mg, 20 mol%), base KOtBu (3.4 mg, 30 mol%), and reaction solvent p-xylene (1.0 mL) were added to a 25 mL reaction tube equipped with a stir bar. The reaction was carried out at 25 °C for 10 min to generate a catalyst pre-stirred solution.

[0069] Step 2: Under an argon protective atmosphere, pinacol diboronate (B2pin2) (compound 2) (76.2 mg, 3.0 eq.) was added to the pre-stirred catalyst solution, and the reaction was carried out at 25 °C for 10 min. Subsequently, 2-phenyl-2,1-borazanaphthalene (compound 1) (21 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) were added sequentially. Finally, the reaction tube was sealed and the reaction was carried out at 100 °C for 12 h. After the reaction was completed, the crude product was purified by silica gel column chromatography to obtain 2-phenyl-4-pinacolboron-2,1-borazanaphthalene (compound 3) in 66% yield.

[0070] Comparative Example 5:

[0071] Comparative Example 5 is basically the same as Example 1, except that potassium carbonate (K2CO3) in step 3 is replaced with potassium tert-butoxide (KOtBu). The specific steps are as follows:

[0072] Step 3: The reaction was carried out in a double-tube system. Under an argon protective atmosphere, 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene (compound 3) (33.2 mg, 1.0 eq.), Xphos-Pd-G2 (1.6 mg, 2 mol%), 5-iodopyrimidine (compound 4) (22.7 mg, 1.1 eq.), KOtBu (33.7 mg, 3.0 eq.), tert-butanol (0.5 mL), and deionized water (0.5 mL) were added to a 25 mL reaction tube equipped with a stir bar. The reaction system was brown. The reaction tube was sealed and reacted at 50±3 °C for 12 h. After the reaction was completed, the mixture was extracted three times with ethyl acetate (EA). The obtained organic phase was washed three times with saturated sodium chloride solution, dried with anhydrous Na2SO4, filtered, and the solvent was evaporated to obtain the crude product. The crude product was then subjected to column chromatography to obtain 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene (compound 5) in 9% yield.

Claims

1. A method for preparing a 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene compound, characterized in that, The specific steps are as follows: Step 1: Under an argon protective atmosphere, add the catalyst CuCl, ligand 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene (Xantphos), base lithium tert-butoxide (LiOtBu), and solvent p-xylene sequentially to a 25 mL reaction tube equipped with a stir bar, and react at 25±3 °C for 10 min to 15 min to generate a light white catalyst pre-stirred solution; Step 2: Under an argon protective atmosphere, pinacol ester (B2pin2) of borate was added to the pre-stirred catalyst solution and reacted at 25±3 °C for 10 min to 15 min. Subsequently, 2-phenyl-2,1-borazanaphthalene and 2-adamantanone were added sequentially. The reaction tube was sealed and reacted at 100±3 °C for 12 h to 72 h. The crude product obtained from the reaction was purified by silica gel column chromatography to obtain 2-phenyl-4-pinacol boron-2,1-borazanaphthalene.

2. The method for preparing the 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene compound according to claim 1, characterized in that, The catalyst CuCl has a molar amount of 15% of 2-phenyl-2,1-borazonaphthalene, the ligand Xantphos has a molar amount of 2-phenyl-2,1-borazonaphthalene, and the base LiOtBu has a molar amount of 30% of 2-phenyl-2,1-borazonaphthalene.

3. The method for preparing the 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene compound according to claim 1, characterized in that, The molar ratio of 2-phenyl-2,1-borazonaphthalene, pinacol diboronate (B2pin2), and 2-adamantanone is 1.0 : 3.0 : 2.5, and the concentration of 2-phenyl-2,1-borazonaphthalene in p-xylene is 0.1 M.

4. The method for preparing the 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene compound according to claim 1, characterized in that, The eluent used in the column chromatography was petroleum ether / ethyl acetate at a volume ratio of 45:

1.

5. A method for preparing a 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound, characterized in that, Includes the following steps: Step 1: Prepare 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene according to any one of claims 1-4; Step 2: Under an argon protective atmosphere, a mixture of tert-butanol (tBuOH) and deionized water (H2O) was added to a 25 mL reaction tube containing 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, catalyst chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (Xphos-Pd-G2), 5-iodopyrimidine, K2CO3, and a stir bar. The reaction tube was sealed and reacted at 50±3 °C for 12 h ~ 18 h. After the reaction was completed, the mixture was extracted with ethyl acetate, the resulting organic phase was washed with saturated sodium chloride solution, dried with anhydrous Na2SO4, filtered, concentrated under reduced pressure to obtain the crude product, and then subjected to column chromatography to obtain 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene molecules.

6. The method for preparing the 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound according to claim 5, characterized in that, The molar amount of the catalyst Xphos-Pd-G2 is 2% of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene.

7. The method for preparing the 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound according to claim 5, characterized in that, The molar ratio of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene, 5-iodopyrimidine to K2CO3 is 1.0 : 1.1 : 3.

0.

8. The method for preparing the 2-phenyl-4-pyrimidinyl-2,1-borazonaphthalene compound according to claim 5, characterized in that, The eluent used in column chromatography was petroleum ether / ethyl acetate at a volume ratio of 6:1, and the concentration of 2-phenyl-4-pinacolboryl-2,1-borazonaphthalene in the tert-butanol / deionized water mixed solvent was 0.1 M.

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