2-phenyl-4-pinacol boryl-2, 1-boron aza-naphthalene, 2-phenyl-4-pyrimidinyl-2, 1-boron aza-naphthalene compound and preparation method of 2-phenyl-4-pinacol boryl-2, 1-boron aza-naphthalene compound

Abstract

The invention discloses 2-phenyl-4-pinacol boryl-2, 1-boron aza-naphthalene, a 2-phenyl-4-pyrimidinyl-2, 1-boron aza-naphthalene compound and a preparation method of the 2-phenyl-4-pinacol boryl-2, 1-boron aza-naphthalene compound, and belongs to the technical field of organic synthetic chemistry. According to the preparation method, 2-phenyl-4-pinacolboryl-2, 1-boronaphthalene and bis (pinacol) diboron diboron ester are taken as raw materials, CuCl is taken as a catalyst, 4, 5-bis (diphenylphosphine)-9, 9-dimethyl xanthene is taken as a ligand, 2-adamantanone is taken as an additive, p-xylene is taken as a solvent, and the 2-phenyl-4-pinacolboryl-2, 1-boronaphthalene is efficiently obtained. The 2-phenyl-4-pyrimidinyl-2, 1-boron aza-naphthalene compound can be used as a key intermediate, the 2-phenyl-4-pyrimidinyl-2, 1-boron aza-naphthalene compound can be conveniently synthesized through efficient conversion of a C-B bond, and a new way is provided for functional modification of the boron-nitrogen heterocyclic compound.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthetic chemistry, and particularly relates to a 2-phenyl-4-pinacolbornyl-2,1-borazaanthracene, a 2-phenyl-4-pyrimidinyl-2,1-borazaanthracene compound and a preparation method thereof. Background Art

[0002] In recent years, more and more research on borazacyclic compounds has attracted people's attention. Among them, 2,1-borazacycles, as a class of unique benzene bioisosteres, have many excellent physical and chemical properties and are widely present in drugs, bioactive molecules, optoelectronic materials and novel ligands. For example, the N-H bond in 2,1-borazacyclic compounds has a donor property and can bind to proteins, which makes it of great value in the field of drug research and development; 2,1-borazacyclic derivatives can be used to prepare materials with special optical properties, etc. Using the bioisosteric B-N bond to simulate the bionic C=C bond to synthesize 1,2-borazacycles has become one of the research hotspots in the chemical community. Therefore, it is very necessary to develop an effective method for synthesizing novel borazacyclic compounds.

[0003] Regarding the synthesis of boron-nitrogen heterocyclic compounds, although some progress has been made, in previous studies, noble metal palladium and iridium catalytic systems were mostly used to synthesize diverse boron-nitrogen heterocyclic compounds (Davies, G. H. M.; Jouffroy, M.; Sherafat, F.; Saeednia, B.; Howshall, C.; Molander, G. A. J. Org. Chem. 2017, 82, 8072-8084. Choi, S.; Dong, G. J. Am. Chem. Soc. 2024, 146, 9512-9518.). The catalysts are relatively expensive and prone to polluting the environment. Additionally, methods where the reaction site occurs 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). The method of the present invention utilizes a copper-catalyzed dehydrogenative borylation strategy to regioselectively introduce a boronic ester group at the C4 position, synthesizing a novel class of boron-nitrogen heterocyclic compounds, which has not been reported yet. Furthermore, as one of the special types of 2,1-borazoles, 2-phenyl-4-pinacolboronic acid-2,1-borazaindene has a relatively reactive boronic ester group in its molecular structure, making the molecule prone to functional group transformation, providing more possibilities for subsequent structural modification and derivatization. Compared with other synthesis methods of various boron-nitrogen heterocyclic compounds, the method described in the present invention is more simple and cost-effective, and is expected to provide important guiding significance and reference value for the synthesis research of structurally diverse boron-nitrogen heterocyclic compounds. Summary of the Invention

[0004] The object of the present invention is to provide a 2-phenyl-4-pinacolboronic acid-2,1-borazaindene, a 2-phenyl-4-pyrimidinyl-2,1-borazaindene compound and a preparation method thereof.

[0005] The following technology is adopted to achieve the object of the present invention: A 2-phenyl-4-pinacolboronic acid-2,1-borazaindene, the structural formula of which is shown as follows: .

[0006] A preparation method of 2-phenyl-4-pinacolboronic acid-2,1-borazaindene, comprising the following steps: Step 1: Under an argon protection atmosphere, successively add the catalyst CuCl, the ligand 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), the base lithium tert-butoxide (LiOtBu), and the solvent p-xylene into a 25 mL reaction tube equipped with a magnetic 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 protection atmosphere, add bis(pinacolato)diboron (B2pin2) to the catalyst pre-stirred solution, and react at 25 ± 3 °C for 10 min to 15 min. Subsequently, successively add 2-phenyl-2,1-borazaanthracene and 2-adamantanone, seal the reaction tube, and react at 100 ± 3 °C for 12 h to 72 h. The crude product obtained from the reaction is purified by silica gel column chromatography to obtain 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1-borazaanthracene.

[0007] In the above technical solution: 2-phenyl-2,1-borazaanthracene and B2pin2 are used as reaction raw materials, CuCl is used as the catalyst, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) is used as the ligand, 2-adamantanone is used as an additive, lithium tert-butoxide (LiOtBu) is used as the base, and p-xylene is used as the solvent. Through a copper-catalyzed selective dehydrogenative borylation strategy, 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1-borazaanthracene is efficiently synthesized.

[0008] Further: In a preparation method of 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1-borazaanthracene, the molar amount of the catalyst CuCl is 15% of 2-phenyl-2,1-borazaanthracene, the molar amount of the ligand Xantphos is 20% of 2-phenyl-2,1-borazaanthracene, and the molar amount of the base LiOtBu is 30% of 2-phenyl-2,1-borazaanthracene.

[0009] Further: In a preparation method of 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1-borazaanthracene, the molar ratio of 2-phenyl-2,1-borazaanthracene, bis(pinacolato)diboron (B2pin2) to 2-adamantanone is 1.0 : 3.0 : 2.5, and the concentration of 2-phenyl-2,1-borazaanthracene in p-xylene is 0.1 M.

[0010] Further: In a preparation method of 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1-borazaanthracene, the eluent used in the column chromatography is petroleum ether / ethyl acetate with a volume ratio of 45:1.

[0011] Further: In a preparation method of 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1-borazaanthracene, the reaction temperature after sealing the reaction tube is 100 ± 3 °C, and the reaction time is 12 h.

[0012] Furthermore, in the preparation method of 2-phenyl-4-pinacolboronic acid-2,1-borazaanthracene, the structural formula of the ligand 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) is as follows: .

[0013] A 2-phenyl-4-pyrimidinyl-2,1-borazaanthracene compound, the structural formula of which is as follows: .

[0014] A preparation method of a 2-phenyl-4-pyrimidinyl-2,1-borazaanthracene compound includes the following steps: Step 1: Under an argon protection atmosphere, successively add the catalyst CuCl, the ligand 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), the base lithium tert-butoxide (LiOtBu), and the solvent p-xylene into a 25 mL reaction tube equipped with a magnetic stirrer, 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 protection atmosphere, add bis(pinacolato)diboron (B2pin2) to the catalyst pre-stirred solution, and react at 25 ± 3 °C for 10 min to 15 min. Subsequently, successively add 2-phenyl-2,1-borazaanthracene and 2-adamantanone, seal the reaction tube, and react at 100 ± 3 °C for 12 h to 72 h. The obtained crude product is purified by silica gel column chromatography to obtain 2-phenyl-4-pinacolboronic acid-2,1-borazaanthracene.

[0015] Step 3: Under an argon protection atmosphere, add a mixed solvent of tert-butanol (tBuOH) and deionized water (H2O) to a 25 mL reaction tube equipped with 2-phenyl-4-pinacolboronic acid-2,1-borazaanthracene, 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, K2CO3, and a magnetic stirrer, seal the reaction tube, and react at 50 ± 3 °C for 12 h to 18 h. After the reaction is completed, extract with ethyl acetate, wash the obtained organic phase with saturated sodium chloride solution, dry with anhydrous Na2SO4, filter, concentrate under reduced pressure to obtain a crude product, and then obtain 2-phenyl-4-pyrimidinyl-2,1-borazaanthracene molecules by column chromatography.

[0016] In the above technical solution: 2-phenyl-4-pinacolboronic acid-2,1-borazaanthracene is further synthesized and transformed to obtain 2-phenyl-4-pyrimidinyl-2,1-borazaanthracene, and the total synthesis route is as follows: .

[0017] Furthermore, in a preparation method of a 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene compound, the CAS number of the catalyst chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (Xphos-Pd-G2) is: 1310584-14-5, and the structural formula is: .

[0018] Furthermore, in a preparation method of a 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene compound, the molar amount of the catalyst Xphos-Pd-G2 is 2% of 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene.

[0019] Furthermore, in a preparation method of a 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene compound, the molar ratio of 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene, 5-iodopyrimidine to K2CO3 is 1.0 : 1.1 : 3.0.

[0020] Furthermore, in a preparation method of a 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene compound, the eluent used in column chromatography is: petroleum ether / ethyl acetate with a volume ratio of 6:1, and the concentration of 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene in the tert-butanol / deionized water mixed solvent is 0.1 M.

[0021] Furthermore, in a preparation method of a 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene compound, the reaction temperature of the tert-butanol (tBuOH) and deionized water (H2O) mixed solvent with 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene, 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 is 50 ± 3 °C, and the reaction time is 12 h.

[0022] Compared with the prior art, the present invention has the following advantages: (1) The present invention uses stable and easily accessible 2-phenyl-2,1-borazaanaphthalene and bis(pinacolato)diboron (B2pin2) as raw materials, and for the first time synthesizes 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene (Compound 3) under simple and feasible reaction conditions, and further performs synthetic transformation on 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene (Compound 3) to obtain 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene (Compound 5) for the first time.

[0023] (2) The present invention utilizes a copper-catalyzed selective dehydrogenative borylation functionalization strategy to enable the borylation reaction of 2-phenyl-2,1-borazaanaphthalene compounds at the C4 position, and for the first time prepares 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene compounds (Compound 3). The method has the advantages of simple operation, environmental friendliness, low cost, stable and easily available raw materials, good regioselectivity of the reaction, and high yield, providing a new idea for the synthesis of novel borazacyclic compounds.

[0024] (3) The 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene compound (Compound 3) synthesized by the present invention can be used as a key intermediate to conveniently synthesize 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene compounds (Compound 5) through efficient transformation of the C-B bond, providing a new approach for the functional modification of borazacyclic compounds. Description of the Drawings

[0025] Figure 1 It is a synthetic route diagram of 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene (Compound 5) prepared in Example 1; Figure 2 It is the 1H NMR spectrum of 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene (Compound 3) prepared in Example 1; Figure 3 It is the 13C NMR spectrum of 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene (Compound 3) prepared in Example 1; Figure 4 It is the 11B NMR spectrum of 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene (Compound 3) prepared in Example 1; Figure 5 It is the 1H NMR spectrum of 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene (Compound 5) prepared in Example 1; Figure 6 It is the 13C NMR spectrum of 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene (Compound 5) prepared in Example 1; Figure 7 It is the 11B NMR spectrum of 2-phenyl-4-pyrimidinyl-–2,1-borazaanaphthalene (Compound 5) prepared in Example 1. Detailed Description of the Invention

[0026] The present invention will be further described in detail below through examples and drawings.

[0027] In the following examples, 2-phenyl-2,1-benzazaborole (Compound 1) was prepared according to the references (Dewar, M. J. S.; Dietz, R. J. Chem. Soc. 1959, 2728 - 2730; Huang, H. N.; Pan, Z. X.; Cui, C. M. Chem. Commun. 2016, 52, 4227 - 4230). Bis(pinacolato)diboron (B2pin2) (Compound 2), catalyst CuCl, ligand 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), additive 2-adamantanone, base lithium tert-butoxide (LiOtBu), potassium carbonate (K2CO3), Xphos-Pd-G2, 5-iodopyrimidine (Compound 4), etc. were all commercially available. Example

[0028] A method for preparing 2-phenyl-4-(pinacolboronic acid)-2,1-benzazaborole and 2-phenyl-4-pyrimidinyl-2,1-benzazaborole compounds: Step 1: The reaction was carried out in a double-tube system. Under an argon atmosphere, 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 magnetic stirrer, and the mixture was reacted at 25 °C for 10 min to form a pale white pre-stirred catalyst solution. Step 2: Under an argon atmosphere, bis(pinacolato)diboron (B2pin2) (Compound 2) (76.2 mg, 3.0 eq.) was added to the pre-stirred catalyst solution, and the mixture was reacted at 25 °C for 10 min. The reaction system turned milky white. Subsequently, 2-phenyl-2,1-benzazaborole (Compound 1) (21 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) were added in sequence, and the reaction system turned yellowish-brown. Finally, the reaction tube was sealed and reacted 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-(pinacolboronic acid)-2,1-benzazaborole (Compound 3) with a yield of 86%. 1 1H 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); 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; 11 B NMR (160 MHz, Chloroform- d ) δ 31.23; HRMS(ESI) m / z: calculated for [C 20 H 23 B2NO2 + Na] + 354.1807, found 354.1812.

[0029] Step 3: The reaction was carried out in a double-tube system. Under an argon atmosphere, 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1-benzoxaborole (Compound Ⅲ) (33.2 mg, 1.0 eq.), Xphos-Pd-G2 (1.6 mg, 2 mol%), 5-iodopyrimidine (Compound Ⅳ) (22.7 mg, 1.1 eq.), K2CO3 (41.5 mg, 3.0 eq.), the reaction solvent tert-butanol (0.5 mL) and deionized water (0.5 mL) were added to a 25 mL reaction tube equipped with a magnetic stirrer. The reaction system turned brown. The reaction tube was sealed and reacted at 50 ± 3 °C for 12 h. After the reaction, it was extracted three times with ethyl acetate (EA). The obtained organic phase was washed three times with saturated sodium chloride solution, dried over anhydrous Na2SO4, filtered, and the solvent was evaporated to obtain the crude product, which was further purified by column chromatography to obtain 2-phenyl-4-pyrimidinyl-2,1-benzoxaborole (Compound Ⅴ) with a yield of 55%; The synthetic route of 2-phenyl-4-pyrimidinyl-2,1-benzoxaborole (Compound Ⅴ) is as follows: .

[0030] 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); 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; 11 B NMR (160 MHz, Chloroform- d ) δ 33.71; HRMS(ESI) m / z: calculated for [C 18 H 14 BN3 + H] + 284.1354, found 284.1362.

[0031] Comparative Example 1: The first and second steps of this Comparative Example 1 are basically the same as those of Example 1. The only difference is that (Compound 1) is replaced with 2-phenyl-3-bromo-2,1-borazaindene (Compound 6). The structural formula of 2-phenyl-3-bromo-2,1-borazaindene (Compound 6) is: .

[0032] The specific steps are as follows: 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%), the ligand Xantphos (12 mg, 20 mol%), the base lithium tert-butoxide LiOtBu (2.4 mg, 30 mol%), the reaction solvent p-xylene (1.0 mL) were added to a 25 mL reaction tube equipped with a magnetic stir bar, and the mixture was reacted at 25 °C for 10 min to form a pre-stirred catalyst solution; Step 2, under an argon protective atmosphere, bis(pinacolato)diboron (B2pin2) (Compound 2) (76.2 mg, 3.0 eq.) was added to the catalyst pre-stirred solution, and the reaction was carried out at 25 °C for 10 min. Subsequently, 2-phenyl-3-bromo-2,1-borazaindene (Compound 6) (28.5 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) were added in sequence. Finally, the reaction tube was sealed and the reaction was carried out at 100 °C for 12 h. Detection by thin layer chromatography (TLC) showed that no obvious spots of the target product 2-phenyl-3-bromo-4-pinacolboranyl-2,1-borazaindene were observed in the reaction system, and the main spot position was consistent with that of the raw material substrate Compound 6.

[0033] Comparative Example 2: This Comparative Example 2 was basically the same as Steps 1 and 2 of Example 1, and the only difference was that the reaction solvent in Step 1 was mesitylene. The specific steps were as follows: Step 1, the reaction was carried out in a double-tube system. Under an argon protective atmosphere, copper(I) chloride (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 mesitylene (1.0 mL) were added to a 25 mL reaction tube equipped with a magnetic stir bar, and the reaction was carried out at 25 °C for 10 min to form a catalyst pre-stirred solution; Step 2, under an argon protective atmosphere, bis(pinacolato)diboron (B2pin2) (Compound 2) (76.2 mg, 3.0 eq.) was added to the catalyst pre-stirred solution, and the reaction was carried out at 25 °C for 10 min. Subsequently, 2-phenyl-2,1-borazaindene (Compound 1) (21 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) were added in sequence. 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-pinacolboranyl-2,1-borazaindene (Compound 3) with a yield of 61%.

[0034] Comparative Example 3: This Comparative Example 3 was basically the same as Steps 1 and 2 of Example 1, and the only difference was the molar ratio of 2-phenyl-2,1-borazaindene (Compound 1), bis(pinacolato)diboron (B2pin2) (Compound 2) to 2-adamantanone in Step 2. The specific steps were as follows: Step 1: The reaction is 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%), reaction solvent p-xylene (1.0 mL) are added to a 25 mL reaction tube equipped with a magnetic stir bar, and the reaction is carried out at 25 °C for 10 min to form a catalyst pre-stirred solution. Step 2: Under an argon protective atmosphere, bis(pinacolato)diboron (B2pin2) (Compound 2) (50.8 mg, 2.0 eq.) is added to the catalyst pre-stirred solution, and the reaction is carried out at 25 °C for 10 min. Subsequently, 2-phenyl-2,1-borazaindole (Compound 1) (21 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) are added in sequence. Finally, the reaction tube is sealed and the reaction is carried out at 100 °C for 12 h. After the reaction is completed, the crude product is purified by silica gel column chromatography to obtain 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1-borazaindole (Compound 3) with a yield of 65%.

[0035] Comparative Example 4: This Comparative Example 4 is basically the same as Steps 1 and 2 of Example 1, and the only difference is that lithium tert-butoxide (LiOtBu) in Step 1 is replaced by potassium tert-butoxide (KOtBu). The specific steps are as follows: Step 1: The reaction is 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%), reaction solvent p-xylene (1.0 mL) are added to a 25 mL reaction tube equipped with a magnetic stir bar, and the reaction is carried out at 25 °C for 10 min to form a catalyst pre-stirred solution. Step 2: Under an argon protective atmosphere, bis(pinacolato)diboron (B2pin2) (Compound 2) (76.2 mg, 3.0 eq.) is added to the catalyst pre-stirred solution, and the reaction is carried out at 25 °C for 10 min. Subsequently, 2-phenyl-2,1-borazaindole (Compound 1) (21 mg, 1.0 eq.) and 2-adamantanone (37.6 mg, 2.5 eq.) are added in sequence. Finally, the reaction tube is sealed and the reaction is carried out at 100 °C for 12 h. After the reaction is completed, the crude product is purified by silica gel column chromatography to obtain 2-phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1-borazaindole (Compound 3) with a yield of 66%.

[0036] Comparative Example 5: This comparative example 5 is basically the same as Example 1, except that potassium carbonate (K2CO3) in step 3 is replaced by potassium tert-butoxide (KOtBu). The specific steps are: Step 3: The reaction was carried out in a double-row tube system. Under an argon atmosphere, 2-phenyl-4-pinacol boryl-2,1-borazine (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.) were added to a 25 mL reaction tube equipped with a stirrer. The reaction solvents were tert-butanol (0.5 mL) and deionized water (0.5 mL). The reaction system turned brown. The reaction tube was sealed and reacted at 50±3°C for 12 h. After the reaction, the mixture was extracted three times with ethyl acetate (EA). The resulting organic phase was washed three times with saturated sodium chloride solution, dried over anhydrous Na2SO4, filtered, and the solvent was spin-dried to obtain the crude product. The crude product was then purified by column chromatography to obtain the 2-phenyl-4-pyrimidinyl-2,1-borazine molecule (compound 5) with a yield of 9%.

Claims

1. A method for preparing a 2-phenyl-4-pinacolboronic acid-2,1-borazaanaphthalene compound, characterized in that, The specific steps are as follows: Step 1: Under an argon protection atmosphere, successively add the catalyst CuCl, the ligand 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), the base lithium tert-butoxide (LiOtBu), and the solvent p-xylene into a 25 mL reaction tube equipped with a magnetic stirrer, and react at 25 ± 3 °C for 10 min to 15 min to generate a light white pre-stirred catalyst solution; Step 2: Under an argon protection atmosphere, add bis(pinacolato)diboron (B2pin2) to the pre-stirred catalyst solution, and react at 25 ± 3 °C for 10 min to 15 min. Subsequently, successively add 2-phenyl-2,1-benzoxaborole and 2-adamantanone, seal the reaction tube, and react at 100 ± 3 °C for 12 h to 72 h. The crude product obtained from the reaction is purified by silica gel column chromatography to obtain 2-phenyl-4-pinacolbornyl-2,1-benzoxaborole.

2. The preparation method of the 2-phenyl-4-pinacolboronic-2,1-borazaanthracene compound according to claim 1, characterized in that The molar amount of the catalyst CuCl is 15% of 2-phenyl-2,1-benzoxaborole, the molar amount of the ligand Xantphos is 20% of 2-phenyl-2,1-benzoxaborole, and the molar amount of the base LiOtBu is 30% of 2-phenyl-2,1-benzoxaborole.

3. The preparation method of the 2-phenyl-4-pinacolboronic-2,1-borazaanaphthalene compound according to claim 1, characterized in that, The molar ratio of 2-phenyl-2,1-benzoxaborole, bis(pinacolato)diboron (B2pin2) to 2-adamantanone is 1.0 : 3.0 : 2.5, and the concentration of 2-phenyl-2,1-benzoxaborole in p-xylene is 0.1 M.

4. The preparation method of the 2-phenyl-4-pinacolboronic group-2,1-borazaphenanthrene compound according to claim 1, characterized in that, The eluent used in the column chromatography is: petroleum ether / ethyl acetate with a volume ratio of 45:

1.

5. A method for preparing a 2-phenyl-4-pyrimidinyl-2,1-borazaindene compound, characterized in that, It includes the following steps: Step 1: Prepare 2-phenyl-4-pinacolbornyl-2,1-benzoxaborole according to any one of the claims 1-4; Step 2: Under an argon protection atmosphere, add a mixed solvent of tert-butanol (tBuOH) and deionized water (H2O) into a 25 mL reaction tube equipped with 2-phenyl-4-pinacolbornyl-2,1-benzoxaborole, 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, K2CO3 and a magnetic stirrer, seal the reaction tube, and react at 50 ± 3 °C for 12 h to 18 h. After the reaction is completed, extract with ethyl acetate, wash the obtained organic phase with saturated sodium chloride solution, dry with anhydrous Na2SO4, filter, concentrate under reduced pressure to obtain a crude product, and then obtain 2-phenyl-4-pyrimidinyl-2,1-benzoxaborole molecules through column chromatography.

6. The preparation method of the 2-phenyl-4-pyrimidinyl-2,1-borazaindene compound according to claim 5, characterized in that, The molar amount of the catalyst Xphos-Pd-G2 is 2% of 2-phenyl-4-pinacolbornyl-2,1-benzoxaborole.

7. The preparation method of the 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene compound according to claim 5, characterized in that, The molar ratio of 2-phenyl-4-pinacolbornyl-2,1-benzoxaborole, 5-iodopyrimidine to K2CO3 is 1.0 : 1.1 : 3.

0.

8. The preparation method of the 2-phenyl-4-pyrimidinyl-2,1-borazaanaphthalene compound according to claim 5, characterized in that, The eluent used in column chromatography is: petroleum ether / ethyl acetate with a volume ratio of 6:1, and the concentration of 2-phenyl-4-pinacolboranyl-2,1-benzoxaborole in the mixed solvent of tert-butanol / deionized water is 0.1 M.

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