Active functional group-containing disubstituted tribranched BODIPY compound, preparation method thereof and nucleophilic substitution product

Abstract

The invention discloses a disubstituted tribranched BODIPY compound containing an active functional group, a preparation method thereof and a nucleophilic substitution product, aromatic aldehyde containing a phenol protecting group is used for synthesizing a fluorescent nucleus, phenolic hydroxyl is obtained through deprotection, then a disubstituted compound containing the active functional group in a side chain is sequentially prepared step by step, and the disubstituted tribranched BODIPY compound containing the active functional group is obtained. A novel disubstituted tribranched BODIPY structure which cannot be prepared so far and contains an aldehyde group or a Boc-group on a side chain can be obtained, and a corresponding trisubstituted product can be obtained after nucleophilic substitution reaction. The side chain aldehyde group and Boc-can respectively provide active sites for further chemical coupling, so that the diversity of molecular structures and physical properties can be increased, the application range of the BODIPY fluorescent compound is expanded, and the BODIPY fluorescent compound particularly has extremely important application value in the field of bimodal imaging probe molecular structure design and preparation. The synthesized product belongs to a fluorescent dye, is easily dissolved in a common organic solvent, and has the characteristics of high fluorescence quantum yield, high molar extinction coefficient, narrow absorption and emission band and the like.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical synthetic dyes, and in particular relates to a disubstituted tris-fluoroboron dipyrrole compound containing an active functional group, a preparation method thereof and a nucleophilic substitution product. Background Art

[0002] The structure of boron dipyrrole (BODIPY) fluorescent dye has the characteristics of high fluorescence quantum yield, high molar extinction coefficient, narrow absorption and emission bands, etc. It is widely used in research fields such as fluorescence labeling, chemical sensors, solar energy conversion and photodynamic therapy. In order to pursue the wider application performance, better photostability, higher fluorescence quantum efficiency and near-infrared emission performance of fluoroboranedipyrrole structure, chemists have carried out a lot of chemical design and synthesis of fluoroboranedipyrrole molecules in three main aspects: pyrrole ring (Jiang, XD; Zhang, HJ; Zhang, YL; Zhao, WL Tetrahedron 2012, 68, 9795.), 8-position derivatives (Lee, HY; Bae, DR; Park, JC; Song, HJ; Han, WS; Jung, JH Angew. Chem. Int. Ed. 2009, 48, 1239.) and replacement of fluorine atoms (Bonardi, L.; Ulrich, G.; Ziessel, R. Org. Lett. 2008, 10, 2183.). In the past decade, fluoroborane dipyrrole structures have attracted attention as optical / nuclear medicine dual-modal imaging probes in the field of molecular imaging technology (Berhard, C.; Goze, C.; Rousselin, Y.; Denat, F. Chem. Commun. 2010, 46(43): 8267; Kim, H.; Kim, K.; Son, SH et al. ACS Chem. Neurosci. 2019, 10: 1445), and the presence of active functional groups in the structure has become a necessary factor in the construction of dual-modal probes.

[0003] The three-branched fluoroborane dipyrrole structure is a type of fluorescent compound with 1,3,5-s-triazine as a three-branched bridging group, which is connected to the fluoroborane dipyrrole fluorophore and the auxiliary group respectively. So far, its synthesis method is: using cyanuric chloride as a raw material, using temperature control, sequentially synthesizing a three-branched intermediate containing an aromatic aldehyde group (a necessary group for condensation), and then introducing the BODIPY fluorescent core at the aromatic aldehyde through condensation, oxidation and coordination processes (Route 1, see Appendix Fig.21), and many research works have been published (Qi, X.; Kim, SK; Han, SJ et al. Supramol. Chem. 2009, 21, 455; Lu, JH,; Qi, X.; Yue, T. et al. Tetrahedron 2015, 71, 1304; Wang, HB; Qi, X.; Huang, TY Synth. Commun. 2022, 52, 1705).

[0004] In the above route, the active groups on other side chain groups of the three-arm intermediate must be stable under acidic condensation, oxidant and boron trifluoride conditions. If a temporary protecting group is selected, the BODIPY fluorescent core also needs to remain stable during the subsequent related deprotection process. These requirements will inevitably greatly restrict the selection range of active functional groups. Therefore, developing a more general three-arm fluoroborane dipyrrole synthesis route that can avoid the above restrictive conditions is of great significance for expanding the diversity of its molecular structure and expanding its application in optical / nuclear medicine dual-modality imaging probes. Summary of the invention

[0005] Technical problems solved: In response to the above technical problems, the present invention provides a disubstituted tri-branched fluoroborane dipyrrole compound containing active functional groups, a preparation method thereof and a nucleophilic substitution product. The synthetic route is more versatile, which allows a wider range of active functional groups to be selected, and can increase the diversity of the tri-branched fluoroborane dipyrrole molecular structure to meet the requirements of application conditions.

[0006] Technical solution: A method for preparing a disubstituted tris-fluoroborane dipyrrole compound containing an active functional group comprises the following steps:

[0007] Step 1. Place fluoroborane dipyrrole containing acetyl group and lithium hydroxide in a water-tetrahydrofuran solution and stir for 0.5-10 hours to obtain fluoroborane dipyrrole containing phenolic hydroxyl group, which is recorded as dye A;

[0008] Step 2. Under ice-water bath and stirring, cyanuric chloride, dye A and diisopropylethylamine are reacted in dichloromethane solution for 0.5-4h to obtain a substitution reaction solution;

[0009] Step 3. Add a substitution reactant having a side chain with an active functional group, diisopropylethylamine and dichloromethane to the substitution reaction solution. The reaction solution is gradually heated to 15° C. within 1 hour. The reaction mixture is concentrated and purified by column chromatography to obtain a disubstituted tris-fluoroborane dipyrrole compound containing an active functional group.

[0010] Preferably, the structural formulas of the dye A and the acetyl-containing fluoroboron dipyrrole in step 1 are respectively:

[0011]

[0012] Among them, R1 is alkyl; R2 is hydrogen or alkyl; R3 is hydrogen, alkyl or alkoxy.

[0013] Furthermore, R1 is methyl; R2 is hydrogen or ethyl; R3 is hydrogen, methyl or ethoxy.

[0014] Preferably, the substitution reactant having a side chain containing an active functional group in step 3 is a p-hydroxybenzaldehyde derivative, and its structural formula is as follows:

[0015]

[0016] Wherein, R4 is hydrogen, alkyl, alkoxy or halogen.

[0017] Furthermore, the structural formula of the disubstituted three-branched fluoroboron dipyrrole compound containing an active functional group is as follows:

[0018]

[0019] Among them, R1 is alkyl; R2 is hydrogen or alkyl; R3 is hydrogen, alkyl or alkoxy; R4 is hydrogen, alkyl, alkoxy or halogen.

[0020] Furthermore, R1 is methyl; R2 is hydrogen or ethyl; R3 is hydrogen, methyl or ethoxy; R4 is hydrogen, alkyl, alkoxy or halogen.

[0021] Preferably, in step 3, the substitution reactant having a side chain containing an active functional group is N-Boc-ethylenediamine.

[0022] Furthermore, the structural formula of the disubstituted three-branched fluoroboron dipyrrole compound containing an active functional group is as follows:

[0023]

[0024] Among them, R1 is alkyl; R2 is hydrogen or alkyl; R3 is hydrogen, alkyl or alkoxy.

[0025] Furthermore, R1 is methyl; R2 is hydrogen or ethyl; R3 is hydrogen, methyl, methoxy or ethoxy.

[0026] Preferably, the molar ratio of the dye A, cyanuric chloride, the substitution reactant having an active functional group in the side chain, and diisopropylethylamine is (0.7-0.95):1:(1.15-3):(5-10).

[0027] The disubstituted three-branched fluoroboron dipyrrole compound containing active functional groups is prepared by the method.

[0028] A trisubstituted product is obtained by nucleophilic substitution of a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group.

[0029] Preferably, the nucleophilic group used for the nucleophilic substitution is a primary amine group, a secondary amine group or a phenol group.

[0030] Furthermore, the nucleophilic group used for the nucleophilic substitution is a diethylamino group.

[0031] Preferably, the process of the nucleophilic substitution is as follows: a disubstituted tris-fluoroborane dipyrrole compound containing an active functional group, a nucleophilic reagent and diisopropylethylamine are reacted in a tetrahydrofuran solution for 4-24 hours, and then separated and purified by thin layer chromatography to obtain the trisubstituted product of the nucleophilic substitution.

[0032] Furthermore, the molar ratio of the disubstituted tris-branched fluoroboron dipyrrole compound containing an active functional group, the nucleophilic reagent and diisopropylethylamine is 1:(1.2-3.0):(3.5-10).

[0033] Beneficial effects: The present invention has the following effects:

[0034] (1) The present invention provides a new synthetic route for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group in the side chain;

[0035] (2) The disubstituted three-branched fluoroborane dipyrrole structure contains a side chain aromatic aldehyde active functional group or a side chain BocNH-functional group, which cannot be synthesized by current methods;

[0036] (3) The synthesis of trisubstituted products demonstrated the chemical reactivity of chlorine atoms in disubstituted trifluoroborane dipyrrole compounds containing active functional groups. The diversity of molecular structure and physical properties can be increased by introducing appropriate nucleophiles, thus expanding the application range of trifluoroborane dipyrrole compounds.

[0037] (4) The synthesized three-branched fluoroborate dipyrrole compound has the general characteristics of fluoroborate dipyrrole fluorescent dyes. However, the presence of side chain active functional groups makes it extremely valuable in the synthesis of optical / nuclear medicine dual-modality imaging probes. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of compound Ⅰa in Example 1 of the present invention;

[0039] Figure 2 is the carbon NMR spectrum of compound Ⅰa in Example 1 of the present invention;

[0040] Figure 3 is a high-resolution mass spectrum of compound Ⅰa in Example 1 of the present invention;

[0041] Figure 4 is the infrared spectrum of compound Ⅰa in Example 1 of the present invention;

[0042] Figure 5 is the hydrogen nuclear magnetic resonance spectrum of compound IIIa-1 in Example 6 of the present invention;

[0043] Figure 6 is the carbon NMR spectrum of compound IIIa-1 in Example 6 of the present invention;

[0044] Figure 7 This is a high-resolution mass spectrum of compound IIIa-1 in Example 6 of the present invention;

[0045] Figure 8 is the infrared spectrum of compound IIIa-1 in Example 6 of the present invention;

[0046] Fig. 9 is the hydrogen nuclear magnetic resonance spectrum of compound IIIa-4 in Example 9 of the present invention;

[0047] Fig.10 is the carbon NMR spectrum of compound IIIa-4 in Example 9 of the present invention;

[0048] Fig.11 This is a high-resolution mass spectrum of compound IIIa-4 in Example 9 of the present invention;

[0049] Fig.12 is the infrared spectrum of compound IIIa-4 in Example 9 of the present invention;

[0050] Fig.13 is the hydrogen nuclear magnetic resonance spectrum of compound IVa in Example 14 of the present invention;

[0051] Fig.14 is the carbon nuclear magnetic resonance spectrum of compound IVa in Example 14 of the present invention;

[0052] Fig.15 This is a high-resolution mass spectrum of compound IVa in Example 14 of the present invention;

[0053] Fig.16 is the infrared spectrum of compound IVa in Example 14 of the present invention;

[0054] Fig.17 is the hydrogen nuclear magnetic resonance spectrum of compound Va-1 in Example 16 of the present invention;

[0055] Fig.18 is the carbon NMR spectrum of compound Va-1 in Example 16 of the present invention;

[0056] Fig.19 is a high-resolution mass spectrum of compound Va-1 in Example 16 of the present invention;

[0057] Fig. 20is the infrared spectrum of compound Va-1 in Example 16 of the present invention;

[0058] Fig.21 It is a roadmap of existing synthetic methods;

[0059] Fig. 22 It is a synthetic method route map of the present invention. DETAILED DESCRIPTION

[0060] The present invention provides a disubstituted tri-branch fluoroboron dipyrrole compound containing an active functional group, a preparation method thereof, and a nucleophilic substitution product. In order to make the purpose, technical scheme, and effect of the present invention clearer and more specific, the present invention is further described in detail with reference to the accompanying drawings and examples. It should be pointed out that the specific implementation described herein is only used to explain the present invention and is not used to limit the present invention. The general structural formula of the disubstituted tri-branch fluoroboron dipyrrole compound containing an aromatic aldehyde functional group is defined as (I); the structure of the fluoroboron dipyrrole raw material containing a phenolic hydroxyl group used in the synthesis, that is, the general structural formula of the aforementioned dye A is (II), and this type of compound is directly used without separation after saponification of the corresponding acetylated structure (acetyl II); the general structural formula of the nucleophilic substitution product of I is (III); the general structural formula of the disubstituted tri-branch fluoroboron dipyrrole compound containing a BocNH-functional group is (IV); the general structural formula of the nucleophilic substitution product of IV is (V).

[0061] Example 1

[0062] A method for preparing a disubstituted tris-fluoroborane dipyrrole compound containing an aromatic aldehyde functional group, the preparation steps are as follows:

[0063] The reaction raw materials are acetyl IIa dye, cyanuric chloride and p-hydroxybenzaldehyde (R4 is hydrogen), wherein the specific chemical structure of acetyl IIa (R1 is methyl; R2 is hydrogen; R3 is methoxy) is as follows:

[0064]

[0065] 1) Add 0.157 g (0.38 mmol) of acetyl IIa and 15 mL of tetrahydrofuran to a 25 mL single-mouth round-bottom flask, add an aqueous solution (5 mL) containing 0.024 g of LiOH (1.0 mmol) at room temperature, and stir for 2 h. After removing tetrahydrofuran from the reaction mixture under reduced pressure, add dichloromethane (20 mL) and 0.1 M HCl (20 mL), wash the organic layer with water, dry it, and concentrate it under reduced pressure to obtain an orange-red solid IIa.

[0066] 2) Dissolve IIa and 0.078g diisopropylethylamine (0.6mmol) in dichloromethane (5mL), add dropwise to dichloromethane (15mL) containing 0.0736g cyanuric chloride (0.4mmol) at 0-2°C with stirring, and react for 30 minutes. Add 0.0732g p-hydroxybenzaldehyde (0.6mmol), 0.104g diisopropylethylamine (0.8mmol) and dichloromethane (10mL), and control the temperature to 15°C within 1h to end. The organic layer is acidified, washed with water, dried, and concentrated under reduced pressure to obtain an orange-red solid, which is further separated by column chromatography (the volume ratio of the developing solvent is ethyl acetate: petroleum ether = 1:4, containing 5% dichloromethane) to obtain a disubstituted tris-fluoroborane dipyrrole compound Ia containing an aromatic aldehyde functional group (0.167g, yield 73%), the structural formula of which is as follows (R4 is hydrogen):

[0067]

[0068] Figure 1 and Figure 2 They are the nuclear magnetic resonance spectra (hydrogen spectrum and carbon spectrum) of the disubstituted three-branched fluoroboron dipyrrole compound Ⅰa containing aromatic aldehyde functional groups, Figure 3 as well as Figure 4 The high-resolution mass spectrum and infrared spectrum of Ia are respectively. The chemical structure of the compound is confirmed through the characterization results of nuclear magnetic resonance spectrum, mass spectrum and infrared spectrum.

[0069] The above-mentioned final product Ⅰa is easily soluble in common organic solvents such as tetrahydrofuran, dichloromethane, chloroform, methanol, ethanol, ethyl acetate, acetonitrile, etc. When the above-mentioned product is dissolved in tetrahydrofuran, the maximum absorption wavelength is 507nm, and the molar extinction absorption number is 56310mol -1 ·dm 3 cm -1 The maximum emission wavelength is 519nm, the fluorescence quantum yield is 0.56, and it can be used as a fluorescent dye. The chlorine atom on the triazine in the structure can be used for further nucleophilic substitution reactions.

[0070] Example 2

[0071] This example is the same as the other steps of the above example 1, except that in step 1), acetyl IIa is replaced by 0.145 g (0.38 mmol) of acetyl IIb, wherein the specific chemical structures of acetyl IIb (wherein R1 is methyl; R2 is hydrogen; R3 is hydrogen) and Ib (R4 is hydrogen) are as follows:

[0072]

[0073] Example 3

[0074] This embodiment is the same as the other steps of the above embodiment 1, except that in step 1), acetyl IIa is replaced by 0.156 g (0.38 mmol) of acetyl IIc, wherein the specific chemical structures of acetyl IIc (wherein R1 is methyl; R2 is hydrogen; R3 is 2,6-dimethyl) and Ic (R4 is hydrogen) are as follows:

[0075]

[0076] Example 4

[0077] This example is the same as the other steps of the above example 1, except that in step 1), acetyl IIa is replaced by 0.178 g (0.38 mmol) of acetyl IId, wherein the specific chemical structures of acetyl IId (wherein R1 is methyl; R2 is ethyl; R3 is methoxy) and Id (R4 is hydrogen) are as follows:

[0078]

[0079] Example 5

[0080] This example is the same as the other steps of the above example 1, except that in step 2), p-hydroxybenzaldehyde is replaced by 0.094 g of 3-chloro-4-hydroxybenzaldehyde (0.6 mmol), wherein Ie (wherein R1 is a methyl group; R2 is a hydrogen group; R3 is a methoxy group, and R4 is a chlorine atom) has the following specific chemical structure:

[0081]

[0082] Example 6

[0083] A method for preparing a trisubstituted tri-branched fluoroboron dipyrrole fluorescent compound IIIa-1 containing an aromatic aldehyde functional group, the preparation steps are as follows:

[0084] The reaction raw materials are dye Ia, diethylamine and diisopropylethylamine, wherein R1 is methyl; R2 is hydrogen; R3 is methoxy; Nu is diethylamine, and the specific chemical structure is as follows:

[0085]

[0086] 1) At room temperature, 0.146 g of diethylamine (0.2 mmol) was added to a mixture of 0.603 g of dye Ia (0.10 mmol) and 0.026 g of diisopropylethylamine (0.2 mmol) in 10 mL of tetrahydrofuran-water (95%:5%, v / v), and the mixture was stirred at 40°C for 4 h.

[0087] 2) After the tetrahydrofuran was removed from the reaction mixture under reduced pressure, dichloromethane (20 mL) and 0.1M HCl (20 mL) were added, and the organic layer was washed with water, dried, and concentrated under reduced pressure to obtain an orange-red solid. After preparative thin layer chromatography (the volume ratio of the developing solvent was ethyl acetate: petroleum ether = 1:5, containing 4% dichloromethane), a trisubstituted tris-branched fluoroboron dipyrrole fluorescent compound IIIa-1 containing an aromatic aldehyde functional group (0.050 g, yield 75%) was obtained.

[0088] Figure 5 as well as Figure 6 They are respectively the nuclear magnetic resonance spectra (hydrogen spectrum and carbon spectrum) of the trisubstituted tri-branched fluoroboron dipyrrole fluorescent compound IIIa-1, Figure 7 as well as Figure 8 They are respectively the high-resolution mass spectrum and infrared spectrum of the tri-substituted tri-branched fluoroborane dipyrrole fluorescent compound IIIa-1. The chemical structure of the compound was confirmed through the characterization results of nuclear magnetic resonance spectroscopy, mass spectrometry and infrared spectroscopy.

[0089] The final product IIIa-1 is easily soluble in common organic solvents such as tetrahydrofuran, dichloromethane, chloroform, methanol, ethanol, ethyl acetate, acetonitrile, etc. The product is dissolved in tetrahydrofuran, and the maximum absorption wavelength is 506nm, and the molar extinction absorption number is 55870mol -1 ·dm 3 cm -1 The maximum emission wavelength is 519nm, the fluorescence quantum yield is 0.55, and it can be used as a fluorescent dye and can be used for coupling reactions with amine groups.

[0090] Example 7

[0091] This example is the same as the other steps of the above example 6, except that in step 1), diethylamine is replaced by 0.200 g N-methylpiperazine (0.2 mmol), wherein IIIa-2 (wherein R1 is methyl; R2 is hydrogen; R3 is methoxy; R4 is hydrogen; Nu is N-methylpiperazinyl) has the following specific chemical structure:

[0092]

[0093] Example 8

[0094] This example is the same as the other steps of the above example 6, except that in step 1), diethylamine is replaced by 0.198 g of glycine methyl ester (0.2 mmol), wherein IIIa-3 (wherein R1 is methyl; R2 is hydrogen; R3 is methoxy; R4 is hydrogen; Nu is glycine methyl ester) has the following specific chemical structure:

[0095]

[0096] Example 9

[0097] This example is the same as the other steps of the above example 6, except that in step 1), diethylamine is replaced with 0.456 g of 4-hydroxybenzoic acid benzyl ester (0.2 mmol), and the reaction is stirred and refluxed for 6 hours. The specific chemical structure of IIIa-4 (wherein R1 is methyl; R2 is hydrogen; R3 is methoxy; R4 is hydrogen; Nu is 4-benzyloxycarbonylphenoxy) is as follows:

[0098]

[0099] Example 10

[0100] This example is the same as the other steps of the above example 6, except that in step 1), dye Ia is replaced by 0.574 g dye Ib (0.10 mmol), wherein IIIb-1 (wherein R1 is methyl; R2 is hydrogen; R3 is hydrogen; R4 is hydrogen; Nu is diethylamino) has the following specific chemical structure:

[0101]

[0102] Embodiment 11

[0103] This example is the same as the above example 6 in other steps, except that in step 1), dye Ia is replaced by 0.602 g dye Ic (0.10 mmol), wherein IIIc-1 (wherein R1 is methyl; R2 is hydrogen; R3 is 2,6-dimethyl; R4 is hydrogen; Nu is diethylamino) has the following specific chemical structure:

[0104]

[0105] Example 12

[0106] This example is the same as the other steps of the above example 6, except that in step 1), dye Ia is replaced by 0.660 g of dye Id (0.10 mmol), wherein IIId-1 (wherein R1 is methyl; R2 is ethyl; R3 is methoxy; R4 is hydrogen; Nu is diethylamino) has the following specific chemical structure:

[0107]

[0108] Example 13

[0109] This example is the same as the other steps of the above example 6, except that in step 1), dye Ia is replaced by 0.638 g of dye Ie (0.10 mmol), wherein IIIe-1 (wherein R1 is a methyl group; R2 is a hydrogen group; R3 is a methoxy group; R4 is a 2-chlorine atom; and Nu is a diethylamino group) has the following specific chemical structure:

[0110]

[0111] Embodiment 14

[0112] A method for preparing a disubstituted tris-branched fluoroboron dipyrrole compound IVa containing a BocNH-functional group, the preparation steps being as follows:

[0113] The preparation process is the same as that of Example 1, except that in step 2), p-hydroxybenzaldehyde is replaced by N-Boc-ethylenediamine hydrochloride (0.094 g, 0.48 mmol), and column chromatography (DCM:MeOH, 100:1) is used to obtain a disubstituted tris-fluoroborane dipyrrole compound IVa containing a BocNH-functional group (0.095 g, yield 82%), the structural formula of which is as follows (wherein R1 is methyl; R2 is hydrogen; and R3 is methoxy):

[0114]

[0115] Fig.13 and Fig.14 They are the nuclear magnetic resonance spectra (hydrogen spectrum and carbon spectrum) of the disubstituted tris-branched fluoroboron dipyrrole compound IVa containing BocNH-functional group, Fig.15 as well as Fig.16 The high-resolution mass spectrum and infrared spectrum of IVa are respectively. The chemical structure of the compound is confirmed through the characterization results of magnetic resonance spectroscopy, mass spectrometry and infrared spectroscopy.

[0116] The final product ⅠVa is easily soluble in common organic solvents such as tetrahydrofuran, dichloromethane, chloroform, methanol, ethanol, ethyl acetate, acetonitrile, etc. The product is dissolved in tetrahydrofuran, and the maximum absorption wavelength is 506nm, and the molar extinction absorption number is 56020mol -1 ·dm 3 cm -1 The maximum emission wavelength is 516nm, the fluorescence quantum yield is 0.55, and it can be used as a fluorescent dye. The chlorine atom on the triazine in the structure can be used for further nucleophilic substitution reactions.

[0117] Embodiment 15

[0118] This example is the same as the other steps of Example 14, except that in step 1), acetyl IIa is replaced by 0.145 g (0.38 mmol) acetyl IIb to obtain IVb (wherein R1 is methyl; R2 is hydrogen; R3 is hydrogen). The specific chemical structure is as follows:

[0119]

[0120] Example 16

[0121] A method for preparing a trisubstituted tribranched fluoroborane dipyrrole compound Va-1 containing a BocNH-functional group, the preparation steps are as follows:

[0122] The reaction raw materials are dye IVa, diethylamine and diisopropylethylamine, wherein R1 is methyl; R2 is hydrogen; R3 is methoxy; Nu is diethylamine, and the specific chemical structure is as follows:

[0123]

[0124] 1) At room temperature, 0.146 g of diethylamine (0.2 mmol) was added to 10 mL of tetrahydrofuran containing 0.642 g of dye IVa (0.10 mmol) and 0.026 g of diisopropylethylamine (0.2 mmol), and the mixture was stirred at 55° C. for 6 h.

[0125] 2) After removing tetrahydrofuran from the reaction mixture under reduced pressure, dichloromethane (20 mL) and 0.1 M HCl (20 mL) were added, and the organic layer was washed with water, dried, and concentrated under reduced pressure to obtain an orange-red solid. After preparative thin layer chromatography (the volume ratio of the developing solvent was ethyl acetate: petroleum ether: methanol = 10:30:0.75), a trisubstituted tris-branched fluoroboron dipyrrole compound Va-1 containing a BocNH-functional group (0.047 g, yield 70%) was obtained.

[0126] Fig.17 and Fig.18 They are respectively the nuclear magnetic resonance spectra (hydrogen spectrum and carbon spectrum) of the trisubstituted tri-branched fluoroborane dipyrrole compound Va-1, Fig.19 and Fig. 20 They are respectively the high-resolution mass spectrum and infrared spectrum of Va-1. The chemical structure of the compound was confirmed through the characterization results of nuclear magnetic resonance spectrum, mass spectrum and infrared spectrum.

[0127] The final product Va-1 is easily soluble in common organic solvents such as tetrahydrofuran, dichloromethane, chloroform, methanol, ethanol, ethyl acetate, acetonitrile, etc. The product is dissolved in tetrahydrofuran, and the maximum absorption wavelength is 505nm, and the molar extinction absorption number is 55330mol -1 ·dm 3 cm -1 The maximum emission wavelength is 515nm, the fluorescence quantum yield is 0.54, and it can be used as a fluorescent dye and can be used for coupling reactions with amine groups.

[0128] Embodiment 17

[0129] This example is the same as the other steps of the above example 16, except that in step 1), diethylamine is replaced by 0.200 g N-methylpiperazine (0.2 mmol), wherein Va-2 (wherein R1 is methyl; R2 is hydrogen; R3 is methoxy; Nu is N-methylpiperazinyl) has the following specific chemical structure:

[0130]

[0131] Embodiment 18

[0132] This example is the same as the above example 16 except that in step 1), dye IVa is replaced by 0.612 g (0.10 mmol) IVb. The specific chemical structure of Vb-1 (wherein R1 is methyl; R2 is hydrogen; R3 is hydrogen; Nu is diethylamino) is as follows:

[0133]

[0134] The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group, characterized in that: The steps include: Step 1. Place fluoroborane dipyrrole containing acetyl group and lithium hydroxide in a water-tetrahydrofuran solution and stir for 0.5-10 hours to obtain fluoroborane dipyrrole containing phenolic hydroxyl group, which is recorded as dye A; Step 2. Under ice-water bath and stirring, cyanuric chloride, dye A and diisopropylethylamine are reacted in dichloromethane solution for 0.5-4h to obtain a substitution reaction solution; Step 3. Add a substitution reactant having a side chain with an active functional group, diisopropylethylamine and dichloromethane to the substitution reaction solution. The reaction solution is gradually heated to 15° C. within 1 hour. The reaction mixture is concentrated and purified by column chromatography to obtain a disubstituted tris-fluoroborane dipyrrole compound containing an active functional group.

2. The method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group according to claim 1, characterized in that: The structural formulas of dye A and acetyl-containing fluoroborane dipyrrole in step 1 are: Among them, R1 is alkyl; R2 is hydrogen or alkyl; R3 is hydrogen, alkyl or alkoxy.

3. The method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group according to claim 2, characterized in that: The R1 is methyl; R2 is hydrogen or ethyl; R3 is hydrogen, methyl or ethoxy.

4. The method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group according to claim 1, characterized in that: In the step 3, the substitution reactant having a side chain containing an active functional group is a p-hydroxybenzaldehyde derivative, and its structural formula is as follows: Wherein, R4 is hydrogen, alkyl, alkoxy or halogen.

5. The method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group according to claim 4, characterized in that: The structural formula of the disubstituted three-branched fluoroboron dipyrrole compound containing an active functional group is as follows: Among them, R1 is alkyl; R2 is hydrogen or alkyl; R3 is hydrogen, alkyl or alkoxy; R4 is hydrogen, alkyl, alkoxy or halogen.

6. The method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group according to claim 5, characterized in that: The R1 is methyl; R2 is hydrogen or ethyl; R3 is hydrogen, methyl or ethoxy; R4 is hydrogen, alkyl, alkoxy or halogen.

7. The method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group according to claim 1, characterized in that: In the step 3, the substitution reactant having a side chain containing an active functional group is N-Boc-ethylenediamine.

8. The method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group according to claim 7, characterized in that: The structural formula of the disubstituted three-branched fluoroboron dipyrrole compound containing an active functional group is as follows: Among them, R1 is alkyl; R2 is hydrogen or alkyl; R3 is hydrogen, alkyl or alkoxy.

9. The method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group according to claim 8, characterized in that: R1 is methyl; R2 is hydrogen or ethyl; R3 is hydrogen, methyl, methoxy or ethoxy.

10. The method for preparing a disubstituted tri-branched fluoroborane dipyrrole compound containing an active functional group according to claim 1, characterized in that: The molar ratio of the dye A, cyanuric chloride, the substitution reactant containing active functional groups in the side chain and diisopropylethylamine is (0.7-0.95):1:(1.15-3):(5-10).

11. A disubstituted tri-branched fluoroboron dipyrrole compound containing an active functional group prepared according to any one of the preparation methods of claims 1 to 10.

12. A trisubstituted product obtained by nucleophilic substitution of the disubstituted tri-branched fluoroboron dipyrrole compound containing an active functional group according to claim 11.

13. The trisubstituted product according to claim 12, characterized in that The nucleophilic group used for the nucleophilic substitution is a primary amine group, a secondary amine group or a phenol group.

14. The trisubstituted product according to claim 13, characterized in that The nucleophilic group used for the nucleophilic substitution is a diethylamino group.

15. The trisubstituted product according to claim 12, characterized in that The process of nucleophilic substitution is as follows: a disubstituted tris-branched fluoroborane dipyrrole compound containing an active functional group, a nucleophilic reagent and diisopropylethylamine are reacted in a tetrahydrofuran solution for 4-24 hours, and then separated and purified by thin layer chromatography to obtain the trisubstituted product of nucleophilic substitution.

16. The trisubstituted product according to claim 15, characterized in that The molar ratio of the disubstituted tris-branched fluoroboron dipyrrole compound containing active functional groups, the nucleophilic reagent and diisopropylethylamine is 1:(1.2-3.0):(3.5-10).

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