A kind of sp 3 -Catalyst for carbon-hydrogen bond primary amination reaction and method for preparing primary amine compounds

Abstract

The present invention provides a catalyst for the primary amination reaction of sp<supgt;3< / supgt>-C-H bonds and a method for preparing primary amine compounds, belonging to the technical field of chemical synthesis. The structure of the catalyst is shown in Formula I. The method for preparing primary amine compounds using this catalyst in the present invention has high generality, wide substrate applicability for the reaction, is environmentally friendly, has mild reaction conditions and is not harsh, and the reaction operation is simple, having potential industrial application prospects.

Description

Technical Field

[0001] The present invention belongs to the technical field of chemical synthesis, and particularly relates to a catalyst for sp 3 -carbon-hydrogen bond primary amination reaction and a method for preparing primary amine compounds. Background Art

[0002] The aliphatic primary amine structure not only widely exists in bioactive molecules (such as amoxicillin, Janumet, Memantine, etc.), but also is an important chemical synthesis intermediate, which is widely used in the synthesis of natural products, pharmaceutical molecules and agrochemicals. In addition, primary amines can also be used as important precursors for further constructing secondary amines, tertiary amines and heterocyclic structures.

[0003]

[0004] Traditional methods for synthesizing primary amines mainly rely on organic transformation reactions of special functional groups, including Gabriel reaction, Leuckart reaction, Curtius rearrangement reaction, Schmidt reaction, reduction reactions of imino groups, azide groups, nitrile groups and nitro groups, etc. However, these methods not only require pre-introduction of pre-functional groups in raw materials, resulting in low atom economy, but also have the disadvantages of harsh reaction conditions, many by-products and environmental unfriendliness. Therefore, developing a highly efficient method for synthesizing primary amine compounds from simple and readily available raw materials has extremely high application value.

[0005] sp 3 -carbon-hydrogen bonds widely exist in natural products and bulk chemical raw materials, and have the advantages of wide sources and simple and readily available raw materials. Therefore, directly synthesizing primary amine compounds starting from sp 3 -carbon-hydrogen bonds has great atom economy and applicability. However, currently reported chemical synthesis methods can only synthesize amine compounds with protecting groups from sp 3 -carbon-hydrogen bonds, and then the corresponding primary amine compounds need to be further deprotected. Moreover, these methods have some obvious disadvantages, such as the use of precious metals (rhodium, iridium), relatively harsh reaction conditions (such as high temperature, inert gas protection, use of highly toxic organic solvents (such as benzene), etc.). So far, there has been no reported chemical method for directly synthesizing primary amine compounds from sp 3 -carbon-hydrogen bonds using an economically available and environmentally friendly catalyst under mild conditions.

[0006] From 2020 to 2022, the F.H. Arnold research group continuously developed methods for synthesizing primary amine compounds by enzyme-catalyzed sp 3 -carbon-hydrogen bonds. By mimicking the P450 enzyme-catalyzed sp 3- The process of biological oxidation of C-H bonds, designing that the iron catalytic center in P450 enzyme can form a nitrene intermediate with the PivONH3OTf amine source, thus realizing sp 3 - C-H bond primary amination reaction. By directed evolution of cytochrome P450 enzyme, different libraries of P450 enzyme variants were obtained, and then the primary amination reactions of benzylic, allylic, propargylic and alkane compounds at sp 3 - C-H bonds were realized, and most substrates had high selectivity and reactivity (J. Am. Chem. Soc. 2020, 142, 23, 10279 - 10283; J. Am. Chem. Soc. 2022, 144, 1, 80 - 85; J. Am. Chem. Soc. 2022, 144, 41, 19097 - 19105).

[0007] However, the above - mentioned method still has the following deficiencies: 1. The reaction substrates are relatively limited. Especially for alkane substrates, both the reaction activity and selectivity are poor, and most products cannot be obtained by separation and purification, so they have no application value;

[0008] 2. This method is not applicable to the direct primary amination modification of complex natural products or bioactive pharmaceutical molecules, nor has it been applied to the direct synthesis of some important pharmaceutical molecules. In addition, the tandem cyclization reaction has not been realized for the efficient construction of cyclic secondary amines and lactam compounds;

[0009] 3. This method requires relatively high reaction conditions and needs to be carried out under strict anaerobic conditions, which is not conducive to industrial scale - up applications.

[0010] Therefore, it is of great significance to further develop a new sp 3 - C-H bond primary amination reaction process with high generality and mild reaction conditions. Summary of the Invention

[0011] The purpose of the present invention is to provide a catalyst for sp 3 - C-H bond primary amination reaction and a method for preparing primary amine compounds.

[0012] The present invention provides the use of the compound shown in Formula I as a catalyst for sp 3 - C-H bond primary amination reaction:

[0013]

[0014] Among them, the fused - ring A is selected from: or none; R a 、R b 、R c 、R d are each independently selected from hydrogen, halogen, alkyl, alkoxy, nitro, carboxylic acid, ester group or R a, R b , R c , R d A ring formed by connecting any two of them; X is N or CR e , R e is selected from an aromatic ring, an aromatic ring with any substituents, or an aromatic heterocycle; M is a metal ion.

[0015] Furthermore, the R a , R b , R c , R d are each independently selected from hydrogen and halogen, and at least one is halogen.

[0016] Furthermore, the M is divalent iron, trivalent iron, divalent cobalt, divalent nickel or divalent manganese.

[0017] Furthermore, the M is divalent iron.

[0018] Furthermore, the fused ring A is X is nitrogen, and the halogen is chlorine or fluorine.

[0019] Furthermore, R a and R d are hydrogen, R b and R c are chlorine.

[0020] Furthermore, the compound shown in formula I is iron octachlorophthalocyanine.

[0021] Furthermore, the sp 3 -carbon-hydrogen bond primary amination reaction is a reaction that uses compound 1 and compound 2 as reactants and generates compound 3 under the action of a catalyst. The reaction formula is as follows:

[0022]

[0023] Among them, R, R 1 , R 2 are each independently any group, or any two or three of R, R 1 , R 2 are connected to form a substituted or unsubstituted ring; R 3 is hydrogen, pivaloyl, acetyl, mesyl, tosyl, sulfonic acid group, nitro or methyl, and A is sulfonic acid, hydrochloric acid, sulfuric acid, acetic acid or none.

[0024] Furthermore, R 3 is pivaloyl, and A is sulfonic acid, preferably trifluoromethanesulfonic acid.

[0025] Furthermore, the conditions of the reaction are: in a solvent, react at 20 - 100 °C for 12 - 120 h;

[0026] And / or, the molar ratio of Compound 1 to Compound 2 is 1:(1-3), the molar ratio of Compound 1 to the catalyst is 100:(2-10), and the concentration of Compound 1 is 0.00625M - 0.05M.

[0027] Furthermore, the temperature of the reaction is 25°C and the reaction time is 12 h;

[0028] And / or, the molar ratio of Compound 1 to Compound 2 is 1:3, the molar ratio of Compound 1 to the catalyst is 100:5, and the concentration of Compound 1 is 0.0125M.

[0029] Furthermore, the solvent is one or a mixture of two or more of acetonitrile, dioxane, water, hexafluoroisopropanol, dichloromethane, and N,N-dimethylformamide.

[0030] Furthermore, the solvent is a mixed solvent of dioxane and water.

[0031] The present invention also provides a method for preparing a primary amine compound, which includes the step of reacting Compound 1 and Compound 2 as reactants under the action of a catalyst to prepare a primary amine compound 3; the reaction formula is as follows:

[0032]

[0033] Wherein, R, R 1 , R 2 are each independently any group, or any two or three of R, R 1 , R 2 are connected to form a substituted or unsubstituted ring; R 3 is hydrogen, pivaloyl, acetyl, mesyl, tosyl, sulfonic acid group, nitro or methyl, and A is sulfonic acid, hydrochloric acid, sulfuric acid, acetic acid or none;

[0034] The catalyst is a compound represented by Formula I:

[0035]

[0036] Among them, the fused ring A is selected from: or none; R a , R b , R c , R d are each independently selected from hydrogen, halogen, alkyl, alkoxy, nitro, carboxylic acid, ester group or a ring formed by connecting any two of R a , R b , R c , R d ; X is N or CR e , R eSelected from an aromatic ring, an aromatic ring or an aromatic heterocycle with any substituents; M is a metal ion.

[0037] Further, the R a , R b , R c , R d Are each independently selected from hydrogen and halogen, and at least one is halogen.

[0038] Further, the M is divalent iron, trivalent iron, divalent cobalt, divalent nickel or divalent manganese.

[0039] Further, the M is divalent iron.

[0040] Further, the fused ring A is X is nitrogen, and the halogen is chlorine or fluorine.

[0041] Further, R a and R d are hydrogen, R b and R c are chlorine.

[0042] Further, the compound shown in formula I is iron octachlorophthalocyanine.

[0043] Further, R 3 is pivaloyl, and A is sulfonic acid, preferably trifluoromethanesulfonic acid.

[0044] Further, the conditions of the reaction are: in a solvent, reacting at 20 - 100 °C for 12 - 120 h;

[0045] And / or, the molar ratio of compound 1 to compound 2 is 1:(1 - 3), the molar ratio of compound 1 to the catalyst is 100:(2 - 10), and the concentration of compound 1 is 0.00625 M - 0.05 M.

[0046] Further, the temperature of the reaction is 25 °C, and the reaction time is 12 h;

[0047] And / or, the molar ratio of compound 1 to compound 2 is 1:3, the molar ratio of compound 1 to the catalyst is 100:5, and the concentration of compound 1 is 0.0125 M.

[0048] Further, the solvent is one or a mixture of two or more of acetonitrile, dioxane, water, hexafluoroisopropanol, dichloromethane, N,N-dimethylformamide.

[0049] Further, the solvent is a mixed solvent of dioxane and water.

[0050] Further, R is a substituted or unsubstituted 5- to 6-membered aromatic ring, 5- to 6-membered heteroaromatic ring, 5- to 6-membered fused 5- to 6-membered aromatic ring, or 5- to 6-membered fused 5- to 6-membered heteroaromatic ring.

[0051] Further, R 1 , R 2 are each independently any group, and the reaction formula is as follows:

[0052]

[0053] wherein, R a , R b , R c , R d , R e are each independently selected from hydrogen or any group other than hydrogen;

[0054] Ring A is selected from:

[0055] Further, the R a , R b , R c , R d , R e are each independently selected from hydrogen, halogen, phenyl substituted with a linear or branched alkyl group of C 1～10 , phenyl, a linear or branched alkyl group of C 1～10 , a linear or branched alkoxy group of C 1～10 ;

[0056] and / or, the R 1 , R 2 are each independently selected from hydrogen, a 3- to 6-membered saturated cycloalkyl group, a linear or branched alkyl group of C 1～10 , phenyl, a linear or branched alkyl group of C 1～10 substituted with phenyl, or R 1 , R 2 are connected to form a ring.

[0057] Further, the reaction conditions are: in a mixed solvent of dioxane and water, reacting at 20-80 °C for 12-120 h, preferably reacting at 25-70 °C for 12-120 h, more preferably reacting at 25-60 °C for 12-120 h.

[0058] Further, R 1 is hydrogen, and R 2 is connected to R to form a ring, and the reaction formula is as follows:

[0059]

[0060] wherein, R f , R g , R h , Ri Each is independently selected from hydrogen or any group other than hydrogen, X is CH2, O or NR', n is any integer from 0 to 6; R' is hydrogen, C 1～18 alkyl, benzyl or an amino protecting group, preferably hydrogen, methyl, ethyl, benzyl, benzoyl or Boc.

[0061] Furthermore, the R f , R g , R h , R i are each independently selected from hydrogen, halogen, phenyl substituted by a straight-chain or branched-chain alkyl group of C 1～10 , phenyl, a straight-chain or branched-chain alkyl group of C 1～10 , a straight-chain or branched-chain alkoxy group of C 1～10 , or two adjacent groups among R f , R g , R h , R i are connected to form a ring.

[0062] Furthermore, the reaction conditions are: in a mixed solvent of dioxane and water, reacting at 25 - 60 °C for 12 - 120 h.

[0063] Furthermore, the R is a substituted or unsubstituted alkenyl group.

[0064] Furthermore, the R is wherein R j , R k , R m are any groups.

[0065] Furthermore, R 1 , R 2 are each independently any groups, and the reaction formula is as follows:

[0066]

[0067] Furthermore, the R 1 , R 2 are each independently selected from hydrogen, a straight-chain or branched-chain alkyl group of C 1～10 ; R j , R k , R m are each independently selected from hydrogen, a straight-chain or branched-chain alkyl group of C 1～10 .

[0068] Furthermore, the reaction conditions are: in dioxane and water, reacting at 20 - 60 °C for 12 - 48 h, preferably reacting at 25 - 40 °C for 12 - 24 h.

[0069] Furthermore, the R is wherein Rn , R p is an arbitrary group.

[0070] Furthermore, R 1 , R 2 are respectively independent arbitrary groups, and the reaction formula is as follows:

[0071]

[0072] Furthermore, the reaction conditions are: reacting in a mixed solvent of dioxane and water at 20 - 60 °C for 12 - 48 h.

[0073] Furthermore, the said R is a substituted or unsubstituted straight-chain or branched-chain alkyl group, and R 1 , R 2 are respectively independent arbitrary groups;

[0074] The substituents are any one or more of halogen, ester group, alkoxy group, phenyl group, and benzyl group.

[0075] Furthermore, the said R is a straight-chain or branched-chain alkyl group of C 1～18 , and R 1 , R 2 are respectively independently selected from hydrogen or a straight-chain or branched-chain alkyl group of C 1～10 ;

[0076] Preferably, R is a straight-chain or branched-chain alkyl group of C 1～10 , and R 1 , R 2 are respectively independently selected from hydrogen or a straight-chain alkyl group of C 1～10 .

[0077] Furthermore, the said R and R 1 are connected to form a ring, and R 2 is hydrogen.

[0078] Furthermore, the said R and R 1 are connected to form a saturated ring, and the reaction formula is as follows:

[0079]

[0080] Among them, Y is CHR”, r is an arbitrary integer from 0 to 12; R” is an arbitrary group, preferably hydrogen, methyl, ethyl or benzyl.

[0081] Furthermore, the reaction conditions are: reacting in a mixed solvent of dioxane and water at 25 - 80 °C for 12 - 48 h.

[0082] Furthermore, the compound 1 is any of the following structures:

[0083]

[0084] Further, R, R 1 , R 2 are connected to form a bridged ring.

[0085] Further, Compound 1 is The reaction formula is as follows:

[0086]

[0087] Further, the reaction conditions are: in a mixed solvent of dioxane and water, reacting at 20 - 80 °C for 12 - 72 h, preferably reacting at 25 °C for 12 h.

[0088] Further, the R is a substituted or unsubstituted alkynyl group.

[0089] Further, the R is wherein R q is any group.

[0090] Further, R 1 , R 2 are each independently any group, and the reaction formula is as follows:

[0091]

[0092] Further, R 1 , R 2 are each independently selected from hydrogen, phenyl, a straight-chain or branched-chain alkyl group of C 1～10 , and R q is selected from hydrogen, phenyl, a straight-chain or branched-chain alkyl group of C 1～10 of.

[0093] Further, the reaction conditions are: in a mixed solvent of dioxane and water, reacting at 20 - 60 °C for 12 - 48 h.

[0094] Further, the structure of the Compound 1 is selected from:

[0095]

[0096] The present invention also provides a method for synthesizing a cyclic secondary amine or lactam compound, comprising the step of cyclizing a primary amine compound prepared by the foregoing method under the action of a base to form a cyclic secondary amine or lactam compound; in the foregoing method for preparing the primary amine compound, R is a substituted or unsubstituted straight-chain or branched-chain alkyl group, and R 1 , R 2 are each independently any group; the substituent is any one or more of halogen, ester group, alkoxy group, phenyl group, and benzyl group.

[0097] Further, R is a substituted C1～5 Linear alkyl group, R 1 , R 2 are each independently any group; the substituent is a halogen or an ester group;

[0098] The reaction formula is as follows:

[0099]

[0100] wherein, X is a halogen or an alkoxy group, and n is an integer from 1 to 3.

[0101] Furthermore, the R 1 is a substituted or unsubstituted phenyl group, R 2 is hydrogen, and n is 1 or 2; the substituent of the substitution is a halogen or a methyl ester group.

[0102] The terms of the present invention: "any two or three of R, R 1 , R 2 are connected to form a substituted or unsubstituted ring", the "ring" therein includes saturated or unsaturated, carbocyclic, heterocyclic, fused ring, bridged ring, etc.

[0103] "Sulfonic acid" refers to an acid containing a sulfonic acid group, including methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, etc.

[0104] "Piv" represents pivaloyl.

[0105] The beneficial effects of the present invention:

[0106] 1. The present invention provides an environmentally friendly chemical method for synthesizing primary amine compounds from sp 3 -carbon-hydrogen bonds by using a specific catalyst. The reaction substrate has a wide applicability, and is not only applicable to conventional sp 3 -carbon-hydrogen bond compounds at the benzylic, allylic, and propargylic positions, but also has good compatibility with respect to the sp 3 -carbon-hydrogen bonds of alkane compounds. The primary amine product can be obtained by separation and purification;

[0107] 2. The method of the present invention can be applied to the direct primary amination modification of complex natural products or active pharmaceutical molecules, as well as the direct synthesis of some important pharmaceutical molecules (such as memantine), and further realizes an intramolecular tandem cyclization reaction to complete the efficient synthesis of cyclic secondary amines and lactam compounds;

[0108] 3. The reaction of the present invention does not need to be carried out under an anaerobic condition, and most of the reactions can be carried out under mild conditions of room temperature and air exposure. The reaction operation is simple and has potential industrial application prospects.

[0109] Obviously, based on the above content of the present invention, according to the common general technical knowledge and conventional means in the art, without departing from the above basic technical idea of the present invention, various other forms of modifications, substitutions or changes can also be made.

[0110] The following is a further detailed description of the above content of the present invention through specific embodiments in the form of examples. However, this should not be construed as limiting the scope of the above subject matter of the present invention to the following examples. All technologies implemented based on the above content of the present invention fall within the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0111] Figure 1 Structures of catalysts C1 - C22 screened for Experimental Example 1.

[0112] Figure 2 Standard curve for calculating the analysis yield of products drawn for quantitative analysis in Experimental Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0113] The raw materials and equipment used in the present invention are all known products and are obtained by purchasing commercially available products.

[0114] In the present invention, iron octachlorophthalocyanine catalyst can be synthesized by known methods, and there are two specific usage methods: one is to use it directly; the other is to obtain a supported catalyst by immobilizing iron octachlorophthalocyanine on silica, and then directly use the supported catalyst.

[0115] Synthesis method of supported iron octachlorophthalocyanine catalyst: Weigh iron octachlorophthalocyanine catalyst (21.1 mg, 5 mol%) into a round-bottom flask, add 70 mL of dry dichloromethane solution, then perform ultrasonic treatment for 5 minutes, add 2 g of silica gel (with a specification of 70 - 200 mesh), stir the reaction mixture at 25°C for 3 h, and remove the solvent by rotary evaporation under reduced pressure. The obtained black-green solid is dried in vacuo at 85°C for 12 h to obtain the supported iron octachlorophthalocyanine catalyst.

[0116] In the examples of the present invention, the separation yield = the amount of the target product purified and separated by column chromatography / the theoretical production amount of the target product × 100%.

[0117] In the examples of the present invention, without special instructions, the purity of the separated product is greater than 99%.

[0118] In the examples of the present invention, catalyst X mol% means that the dosage of the catalyst accounts for X% of the molar percentage of compound 1.

[0119] General Synthesis Process 1:

[0120]

[0121] In a dry round-bottom flask, supported catalyst iron octachlorophthalocyanine (5 mol%, supported on 2 g of silica), compound 1 (0.5 mmol), dioxane solvent (2 mL), and an aqueous solution (38 mL) of nitrogen source 2 (1.5 mmol) were added successively. The reaction mixture was stirred at 20 - 100 °C for 12 - 120 h and monitored by TLC or GC-MS until compound 1 was completely consumed to form the primary amine product. Then, the solvent was removed by rotary evaporation under reduced pressure, and the primary amine product 3 (present in the form of trifluoromethanesulfonate) was obtained by column chromatography purification.

[0122] General synthetic process two:

[0123]

[0124] In a dry round-bottom flask, catalyst iron octachlorophthalocyanine (5 mol%), compound 1 (0.5 mmol), dioxane solvent (2 mL), and an aqueous solution (38 mL) of nitrogen source 2 (1.5 mmol) were added successively. The reaction mixture was stirred at 20 - 100 °C for 12 - 120 h and monitored by TLC or GC-MS until compound 1 was completely consumed to form the primary amine product 3. Under ice bath conditions, aqueous NaOH solution and benzoyl chloride were added successively, and the mixture was stirred at room temperature and monitored by TLC or GC-MS until the first-step primary amination product was completely converted. The aqueous phase was extracted with ethyl acetate, and the organic phase was washed successively with saturated sodium bicarbonate and saturated brine, and then dried by rotary evaporation under reduced pressure. Column chromatography purification was carried out to obtain the benzoyl-protected product 3'. (Note: In some examples, protecting the primary amine product with benzoyl group can obtain a higher separation yield)

[0125] Representative specific examples are as follows:

[0126] Example 1, Synthesis of

[0127] The general synthetic process one was adopted. The reaction mixture was stirred at 25 °C for 12 h. After post-treatment, 109.9 mg of the primary amine salt was obtained, property: white solid, separation yield: 76%. Melting point: 96 - 98 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 8.34 - 8.10 (m, 2H), 8.01 - 7.82 (m, 2H), 5.61 (s, 3H, NH3), 5.21 (q, J = 6.9 Hz, 1H), 2.35 (d, J = 6.9 Hz, 3H); 1313C NMR (100 MHz, CD3OD): δ (ppm) 163.7 (d, J = 246.9 Hz), 134.9 (d, J = 3.3 Hz), 129.3 (d, J = 8.5 Hz), 121.1 (q, J = 318.2 Hz), 116.4 (d, J = 22.0 Hz), 51.0, 19.8; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -79.40, -113.89--113.98 (m); HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C8H 11 FN + 140.0870; Found 140.0867.

[0128] Example 2, Synthesis of

[0129] Using General Synthetic Procedure 2. The reaction solution was stirred at 25 °C for 12 h. After workup, 103.4 mg of the benzoyl-protected product was obtained. Appearance: white solid. Isolated yield: 85%. Melting point: 110-112 °C; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.76 (d, J = 7.0 Hz, 2H), 7.54-7.47 (m, 1H), 7.46-7.40 (m, 2H), 7.40-7.34 (m, 2H), 7.13-6.89 (m, 2H), 6.28 (d, J = 7.6 Hz, 1H), 5.46-5.22 (m, 1H), 1.60 (d, J = 6.9 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.6, 162.0 (d, 1 J FC = 245.5 Hz), 139.0 (d, 4 J FC = 3.4 Hz), 134.4, 131.6, 128.6, 127.9 (d, 3 J FC = 8.1 Hz), 126.9, 115.5 (d, 2 J FC = 21.4 Hz), 48.6, 21.8; 19 19F NMR (376 MHz, CDCl3): δ (ppm) -115.13--115.31 (m); HRMS (ESI-TOF) m / z: Calcd for C 15 H 14 FNO+Na +266.0952, found 266.0948.

[0130] Example 3 Synthesis of

[0131] The general synthesis process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 109.6 mg of primary amine salt was obtained. Property: white solid, isolation yield: 81%. Melting point: 115 - 117 °C; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.52 - 7.33 (m, 5H), 4.92 (s, 3H, NH3), 4.46 (q, J = 6.9 Hz, 1H), 1.63 (d, J = 6.9 Hz, 3H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 138.1, 128.9, 128.8, 126.3, 120.4 (q, J = 318.4 Hz), 51.0, 19.3; 19 F NMR (376 MHz, CD3OD): δ (ppm) -80.03; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C8H 12 N + 122.0964; Found 122.0958.

[0132] Example 4 Synthesis of

[0133] The general synthesis process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 109.8 mg of primary amine salt was obtained. Property: white solid, isolation yield: 72%. Melting point: 141 - 143 °C; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.53 - 7.38 (m, 4H), 4.89 (s, 3H, NH3), 4.48 (q, J = 6.8 Hz, 1H), 1.62 (d, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 136.8, 134.7, 129.0, 128.1, 120.4 (q, J = 318.3 Hz), 50.3, 19.1; 19 F NMR (376 MHz, CD3OD): δ (ppm) -80.03; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C8H 11 35 ClN +156.0575; Found 156.0582; Calcd for C8H 11 37 ClN + 158.0546; Found 158.0550.

[0134] Example 5, Synthesis

[0135] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and after post-treatment, 120.9 mg of primary amine salt was obtained. Appearance: white solid, isolation yield: 69%. Melting point: 104 - 106 °C; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.62 (s, 1H), 7.50 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.32 (t, J = 7.8 Hz, 1H), 4.96 (s, 3H, NH3), 4.29 (q, J = 6.8 Hz, 1H), 1.52 (d, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 143.9, 131.0, 130.5, 129.2, 125.0, 122.4, 120.4 (q, J = 318.5 Hz), 50.4, 20.9; 19 F NMR (376 MHz, CD3OD): δ (ppm) -79.98; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C8H 11 79 BrN + 200.0070; Found 200.0072; Calcd for C8H 11 81 BrN + 202.0049; Found 202.0048.

[0136] Example 6, Synthesis

[0137] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and after post-treatment, 135.6 mg of primary amine salt was obtained. Appearance: white solid, isolation yield: 68%. Melting point: 170 - 172 °C; 11H NMR (400 MHz, CD3OD): δ (ppm) 7.82 (d, J = 7.9 Hz, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H), 6.96 (t, J = 7.6 Hz, 1H), 4.87 (s, 3H, NH3), 4.30 (q, J = 6.6 Hz, 1H), 1.34 (d, J = 6.6 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 148.2, 139.4, 128.6, 128.5, 125.7, 98.2, 54.7, 22.6; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.11; HRMS (ESI-TOF) m / z: [M - TfOH + Na] + Calcd for C8H 10 INNa + 269.9750; Found 269.9742.

[0138] Example 7, Synthesis of

[0139] The general synthetic process I was adopted. The reaction solution was stirred at 40 °C for 12 h. After work-up, 118.9 mg of the primary amine salt was obtained. Appearance: white solid, isolation yield: 75%. Melting point: 133 - 135 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 8.32 (d, J = 8.8 Hz, 2H), 7.75 (d, J = 8.8 Hz, 2H), 4.87 (s, 3H, NH3), 4.67 (q, J = 6.9 Hz, 1H), 1.70 (d, J = 6.9 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 148.2, 145.0, 127.8, 123.9, 120.4 (q, J = 317.9 Hz), 50.3, 19.1; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -79.98; HRMS (ESI-TOF) m / z: [M - TfO] + Calcd for C8H 11 N2O2 + 167.0815; Found 167.0820.

[0140] Example 8, Synthesis of

[0141] General synthetic process one was adopted. The reaction solution was stirred at 60 °C for 12 h. After post-treatment, the crude product was obtained, dissolved in 5 mL of dichloromethane, and trifluoromethanesulfonic acid (48 μL, 0.6 mmol) was added dropwise under ice bath conditions. After stirring at room temperature for one hour, the solvent was removed by rotary evaporation under reduced pressure, and column chromatography purification was carried out to obtain 108.5 mg of primary amine salt. Appearance: brown liquid, separation yield: 69%; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 8.06 (d, J = 8.2 Hz, 1H), 7.89 - 7.74 (m, 2H), 7.71 - 7.59 (m, 1H), 4.98 - 4.93 (m, 1H), 4.92 (s, 3H, NH3), 1.69 (d, J = 6.8 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 148.7, 134.1, 132.4, 130.1, 127.4, 125.1, 120.4 (q, J = 318.3 Hz), 46.0, 18.6; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.10; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C8H 11 N2O2 + 167.0815; Found 167.0808.

[0142] Example 9, Synthesis of

[0143] General synthetic process one was adopted. The reaction solution was stirred at 40 °C for 12 h. After post-treatment, 103.3 mg of primary amine salt was obtained. Appearance: colorless liquid, separation yield: 70%; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.69 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 4.87 (s, 3H, NH3), 4.11 (q, J = 6.8 Hz, 1H), 1.39 (d, J = 6.8 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 152.6, 132.1, 126.7, 118.4, 110.2, 50.7, 23.6; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.12; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C9H 11 N2 +147.0917; Found 147.0926.

[0144] Example 10, Synthesis

[0145] General synthetic process two was adopted. The reaction solution was stirred at 60 °C for 24 h. Due to the formation of imine by-products, after post-treatment, the crude product was dissolved in a mixed solution of 15 mL of dioxane and water (1:1), and stirred at 40 °C overnight. After the reaction, the pH was adjusted to 10 with an aqueous sodium hydroxide solution, and monitored by TLC until the imine by-products were completely converted. The aqueous phase was extracted with ethyl acetate and rotary evaporated under reduced pressure. Column chromatography purification was carried out to obtain 62.8 mg of the benzoyl-protected product, property: white solid, isolation yield: 47%. Melting point: 169 - 171 °C; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.99 - 7.86 (m, 2H), 7.85 - 7.74 (m, 2H), 7.53 - 7.38 (m, 5H), 6.62 (d, J = 7.7 Hz, 1H), 5.43 - 5.28 (m, 1H), 2.57 (s, 3H), 1.60 (d, J = 6.9 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 197.7, 166.8, 148.8, 136.2, 134.2, 131.7, 128.8, 128.6, 127.0, 126.7, 126.3, 49.2, 46.0, 26.6, 21.9; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 17 H 17 NNaO2 + 290.1151; Found 290.1149.

[0146] Example 11, Synthesis

[0147] General synthetic process one was adopted. The reaction solution was stirred at 25 °C for 16 h. After post-treatment, 139.3 mg of the primary amine salt was obtained, property: white solid, isolation yield: 85%. Melting point: 122 - 124 °C; 1 1H NMR (400 MHz, CD3CN): δ (ppm) 8.08 (d, J = 8.4 Hz, 2H), 7.94 (s, 3H, NH3), 7.59 (d, J = 8.4 Hz, 2H), 4.71 - 4.54 (m, 1H), 3.91 (s, 3H), 1.66 (d, J = 6.9 Hz, 3H); 1313C NMR (100 MHz, CD3CN): δ (ppm) 167.0, 145.3 - 140.6 (m), 131.8, 130.7, 128.1, 52.7, 52.6 - 52.2 (m), 24.4 - 16.4 (m); 19 19F NMR (376 MHz, CD3CN): δ (ppm) -79.51; HRMS (ESI-TOF) m / z: [M - TfO] + Calcd for C 10 H 14 NO2 + 180.1019; Found 180.1022.

[0148] Example 12, Synthesis

[0149] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 121.6 mg of the primary amine salt was obtained. Appearance: white solid. Isolated yield: 81%. Melting point: 111 - 113 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.43 - 7.26 (m, 2H), 7.09 (d, J = 8.3 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 4.98 (s, 3H, NH3), 4.64 (q, J = 6.9 Hz, 1H), 3.91 (s, 3H), 1.62 (d, J = 6.9 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 157.0, 130.3, 127.1, 125.3, 120.7, 120.4 (q, J = 318.5 Hz), 111.0, 54.7, 47.1, 17.5; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.01; HRMS (ESI-TOF) m / z: [M - TfO] + Calcd for C9H 14 NO + 152.1070; Found 152.1070.

[0150] Example 13, Synthesis

[0151] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 105.6 mg of the primary amine salt was obtained. Appearance: white solid. Isolated yield: 74%. Melting point: 92 - 94 °C; 11H NMR (400 MHz, CD3OD): δ (ppm) 7.38 (d, J = 8.7 Hz, 2H), 6.97 (d, J = 8.7 Hz, 2H), 4.95 (s, 3H, NH3), 4.04 (s, 2H), 3.80 (s, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 160.5, 130.2, 124.8, 120.4 (q, J = 318.4 Hz), 114.1, 54.4, 42.6; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.03; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C8H 12 NO + 138.0913; Found 138.0917.

[0152] Example 14, Synthesis

[0153] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 109.3 mg of the primary amine salt was obtained. Appearance: white solid. Isolated yield: 73%. Melting point: 114 - 116 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.39 (d, J = 8.7 Hz, 2H), 6.98 (d, J = 8.7 Hz, 2H), 4.88 (brs, 3H, NH3), 4.41 (q, J = 6.9 Hz, 1H), 3.80 (s, 3H), 1.61 (d, J = 6.9 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 160.3, 129.9, 127.8, 120.4 (q, J = 318.4 Hz), 114.2, 54.5, 50.5, 19.1; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.01; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C9H 14 NO + 152.1070; Found 152.1071.

[0154] Example 15, Synthesis

[0155] The general synthesis process I was adopted. The reaction solution was stirred at 25 °C for 24 h, and 126.2 mg of primary amine salt was obtained after post-treatment. Appearance: yellow liquid, isolation yield: 80%; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.45 (d, J = 8.9 Hz, 2H), 6.99 (d, J = 8.9 Hz, 2H), 4.89 (brs, 3H, NH3), 3.80 (s, 3H), 1.71 (s, 6H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 159.8, 133.3, 125.8, 120.4 (q, J = 318.4 Hz), 113.9, 55.3, 54.4, 26.6; 19 F NMR (376 MHz, CD3OD): δ (ppm) -80.06; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd forC 10 H 16 NO + 166.1226; Found 166.1225.

[0156] Example 16, Synthesis of

[0157] The general synthesis process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and 123.4 mg of primary amine salt was obtained after post-treatment. Appearance: semi-solid, isolation yield: 75%; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.21 - 6.94 (m, 3H), 4.99 (s, 3H, NH3), 4.32 (q, J = 6.8 Hz, 1H), 2.64 (q, J = 7.6 Hz, 4H), 1.57 (d, J = 6.8 Hz, 3H), 1.23 (t, J = 7.6 Hz, 6H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 145.2, 139.8, 127.5, 122.9, 120.4 (q, J = 318.4 Hz), 51.1, 28.4, 20.3, 14.8; 19 F NMR (376 MHz, CD3OD): δ (ppm) -79.97; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 12 H 20 N + 178.1590; Found 178.1583.

[0158] Example 17 Synthesis

[0159] General synthetic process one was adopted. The reaction solution was stirred at 60 °C for 12 h. After post-treatment, the crude product was obtained, dissolved in 5 mL of dichloromethane, and trifluoromethanesulfonic acid (48 μL, 0.6 mmol) was added dropwise under ice bath conditions. After stirring at room temperature for one hour, the solvent was removed by rotary evaporation under reduced pressure, and column chromatography purification was carried out to obtain 90.2 mg of the primary amine salt. Appearance: white solid, isolation yield: 50%. Melting point: 110 - 112 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.75 (d, J = 6.8 Hz, 1H), 7.50 (d, J = 9.8 Hz, 1H), 4.89 - 4.78 (m, 4H, NH3+CH), 1.62 (d, J = 6.9 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 157.2 (d, J = 249.7 Hz), 136.4 (d, J = 6.3 Hz), 131.6, 128.3 (d, J = 3.8 Hz), 122.1 (d, J = 19.0 Hz), 120.4 (q, J = 318.5 Hz), 114.9 (d, J = 24.3 Hz), 47.1, 18.1; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.10, -110.07--125.97 (m); HRMS (ESI-TOF) m / z: [M - TfOH + Na] + Calcd for C8H8 35 Cl2FNNa + 229.9911; Found 229.9913; Calcd for C8H8 37 Cl2FNNa + 231.9881; Found 231.9887.

[0160] Example 18 Synthesis

[0161] General synthetic process one was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 103.3 mg of the primary amine salt was obtained. Appearance: white solid, isolation yield: 69%. Melting point: 122 - 124 °C; 11H NMR (400 MHz, CD3OD): δ (ppm) 7.54 - 7.29 (m, 5H), 4.97 (s, 3H, NH3), 4.23 (dd, J = 9.0 Hz, 6.2 Hz, 1H), 2.04 - 1.82 (m, 2H), 1.35 - 1.11 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 139.5, 128.7, 128.2, 126.7, 120.4 (q, J = 318.4 Hz), 55.5, 37.7, 18.8, 12.6; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -79.96; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 10 H 16 N + 150.1277; Found 150.1275.

[0162] Example 19, Synthesis

[0163] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After work-up, 99.3 mg of the primary amine salt was obtained. Appearance: white solid. Isolated yield: 66%. Melting point: 97 - 99 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.56 - 7.33 (m, 5H), 5.00 (s, 3H, NH3), 2.13 - 1.97 (m, 2H), 1.70 (s, 3H), 0.80 (t, J = 7.5 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 140.3, 128.7, 128.0, 124.9, 120.4 (q, J = 318.4 Hz), 59.0, 33.8, 23.6, 7.0; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.02; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 10 H 16 N + 150.1277; Found 150.1275.

[0164] Example 20, Synthesis

[0165] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and after post-treatment, 128.4 mg of the primary amine salt was obtained. Appearance: colorless liquid, isolation yield: 86%; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.55 - 7.28 (m, 5H), 4.98 (s, 3H, NH3), 3.46 (d, J = 9.7 Hz, 1H), 1.38 - 1.29 (m, 1H), 0.81 - 0.70 (m, 1H), 0.65 - 0.48 (m, 2H), 0.43 - 0.29 (m, 1H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 137.5, 127.3, 126.9, 125.3, 119.1 (q, J = 318.5 Hz), 59.0, 14.3, 2.6, 1.4; 19 F NMR (376 MHz, CD3OD): δ (ppm) -79.98; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 10 H 14 N + 148.1121; Found 148.1126.

[0166] Example 21, Synthesis of

[0167] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and after post-treatment, 150.3 mg of the primary amine salt was obtained. Appearance: colorless liquid, isolation yield: 74%; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.52 (d, J = 8.8 Hz, 2H), 7.46 (d, J = 8.8 Hz, 2H), 4.90 (s, 3H, NH3), 2.24 - 2.02 (m, 2H), 1.85 - 1.63 (m, 4H), 1.59 - 1.38 (m, 4H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 144.3, 131.3, 127.7, 120.7, 120.4 (q, J = 318.5 Hz), 54.6, 37.0, 25.1, 21.9; 19 F NMR (376 MHz, CD3OD): δ (ppm) -79.95; HRMS (ESI-TOF) m / z: [M-TfOH+Na] + Calcd for C 12 H 16 79 BrNNa+ 276.0359; Found 276.0361; Calcd for C 12 H 16 81 BrNNa + 278.0338; Found 278.0346.

[0168] Example 22, Synthesis

[0169] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 24 h, and the crude product was obtained after post-treatment. It was dissolved in 5 mL of dichloromethane, and trifluoromethanesulfonic acid (48 μL, 0.6 mmol) was added dropwise under ice bath conditions. After stirring at room temperature for one hour, the solvent was removed by rotary evaporation under reduced pressure, and column chromatography purification was carried out to obtain 140.1 mg of primary amine. Appearance: brown solid, isolation yield: 76%. Melting point: 144 - 146 °C; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.42 - 7.29 (m, 8H), 7.29 - 7.23 (m, 1H), 5.27 (s, 1H), 4.90 (s, 3H, NH3); 13 C NMR (100 MHz, CD3OD): δ (ppm) 142.3, 141.6, 132.9, 128.44, 128.41, 128.35, 127.4, 126.7, 120.4 (d, J = 318.6 Hz), 58.3; 19 F NMR (376 MHz, CD3OD): δ (ppm) -80.01; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 13 H 13 35 ClN + 218.0732; Found 218.0734; Calcd for C 13 H 13 37 ClN + 220.0702; Found 220.0697.

[0170] Example 23, Synthesis

[0171] The general synthetic process I was adopted. The reaction solution was stirred at 80 °C for 24 h, and 140.7 mg of primary amine salt was obtained after post-treatment. Appearance: yellow solid, isolation yield: 75%. Melting point: 184 - 186 °C; 11H NMR (400 MHz, CD3OD): δ (ppm) 7.68 (d, J = 8.4 Hz, 2H), 7.61 - 7.45 (m, 4H), 7.28 (d, J = 8.2 Hz, 2H), 4.95 (s, 3H, NH3), 4.47 (q, J = 6.8 Hz, 1H), 2.67 (q, J = 7.6 Hz, 2H), 1.65 (d, J = 6.9 Hz, 3H), 1.25 (t, J = 7.6 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 143.8, 141.8, 137.4, 137.3, 128.1, 127.1, 126.7, 126.5, 120.4 (q, J = 318.4 Hz), 50.7, 28.1, 19.5, 14.8; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.01; HRMS (ESI-TOF) m / z: [M - TfOH + Na] + Calcd for C 16 H 19 NNa + 248.1410; Found 248.1417.

[0172] Example 24, Synthesis

[0173] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 16 h. After post-treatment, the crude product was obtained, dissolved in 5 mL of dichloromethane, and trifluoromethanesulfonic acid (48 μL, 0.6 mmol) was added dropwise under ice bath conditions. After stirring at room temperature for one hour, the solvent was removed by rotary evaporation under reduced pressure, and column chromatography purification was carried out to obtain 144.9 mg of primary amine, property: colorless liquid, separation yield: 83%; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.34 - 7.25 (m, 4H), 7.25 - 7.18 (m, 3H), 7.17 - 7.12 (m, 1H), 7.08 (d, J = 6.8 Hz, 2H), 4.87 (s, 3H, NH3), 4.10 (t, J = 7.2 Hz, 1H), 2.96 (d, J = 7.2 Hz, 2H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 144.1, 138.5, 129.1, 128.01, 127.95, 126.8, 126.4, 126.0, 57.5, 45.3; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.06; HRMS (ESI-TOF) m / z: [M - TfO]+ Calcd for C 14 H 16 N + 198.1277; Found 198.1279.

[0174] Example 25, Synthesis of

[0175] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 24 h, and after post-treatment, 90.1 mg of primary amine salt was obtained. Property: white solid, isolation yield: 67%. Melting point: 136 - 138 °C; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.39 (t, J = 7.2 Hz, 1H), 7.36 - 7.25 (m, 2H), 7.21 (d, J = 7.2 Hz, 1H), 4.91 (s, 3H, NH3), 4.78 (dd, J = 5.0 Hz, 2.1 Hz, 1H), 3.68 (dd, J = 14.6 Hz, 5.0 Hz, 1H), 3.22 (dd, J = 14.6 Hz, 2.1 Hz, 1H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 142.2, 140.7, 130.4, 127.8, 123.3, 122.6, 49.5, 36.0; 19 F NMR (376 MHz, CD3OD): δ (ppm) -80.09; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C8H 10 N + 120.0808; Found 120.0801.

[0176] Example 26, Synthesis of

[0177] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and after post-treatment, 112.7 mg of primary amine salt was obtained. Property: white solid, isolation yield: 80%. Melting point: 143 - 145 °C; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.48 (d, J = 7.4 Hz, 1H), 7.42 - 7.32 (m, 2H), 7.33 - 7.24 (m, 1H), 4.89 (s, 3H, NH3), 4.76 (dd, J = 7.8 Hz, 5.0 Hz, 1H), 3.21 - 3.11 (m, 1H), 3.09 - 2.93 (m, 1H), 2.68 - 2.53 (m, 1H), 2.15 - 1.98 (m, 1H);13 13C NMR (100 MHz, CD3OD): δ (ppm) 144.0, 138.6, 129.3, 126.9, 125.0, 124.0, 55.6, 30.4, 29.6; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -79.98; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C9H 12 N + 134.0964; Found 134.0966.

[0178] Example 27, Synthesis of

[0179] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 121.9 mg of the primary amine salt was obtained. Appearance: white solid. Isolated yield: 82%. Melting point: 116 - 118 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.47 - 7.35 (m, 1H), 7.34 - 7.10 (m, 3H), 4.99 (s, 3H, NH3), 4.47 (t, J = 5.4 Hz, 1H), 3.06 - 2.62 (m, 2H), 2.28 - 2.06 (m, 1H), 2.06 - 1.72 (m, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 137.7, 131.8, 129.5, 128.5, 128.1, 126.3, 120.4 (q, J = 318.5 Hz), 48.9, 28.3, 27.8, 18.1; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.00; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 10 H 14 N + 148.1121; Found 148.1129.

[0180] Example 28, Synthesis of

[0181] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 116.9 mg of the primary amine salt was obtained. Appearance: white solid. Isolated yield: 75%. Melting point: 162 - 164 °C; 11H NMR (400 MHz, CD3OD): δ (ppm) 7.30 - 7.12 (m, 4H), 4.95 (s, 3H, NH3), 4.47 (dd, J = 10.0 Hz, 1.6 Hz, 1H), 2.94 - 2.78 (m, 2H), 2.08 - 1.81 (m, 4H), 1.74 - 1.58 (m, 1H), 1.45 - 1.33 (m, 1H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 141.1, 139.1, 129.7, 127.5, 126.2, 122.9, 120.4 (q, J = 318.4 Hz), 53.9, 34.9, 33.8, 28.2, 26.8; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.03; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 11 H 16 N + 162.1277; Found 162.1280.

[0182] Example 29, Synthesis of

[0183] General synthetic process 1 was adopted. The reaction solution was stirred at 60 °C for 12 h. After post-treatment, 71.8 mg of primary amine salt was obtained. Appearance: semi-solid, isolation yield: 45%; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.75 - 7.64 (m, 1H), 7.61 (d, J = 8.2 Hz, 1H), 7.56 - 7.34 (m, 3H), 7.28 (d, J = 6.8 Hz, 1H), 5.00 - 4.77 (m, 4H), 3.75 (dd, J = 17.6 Hz, 7.8 Hz, 1H), 3.10 (dd, J = 17.6 Hz, 2.9 Hz, 1H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 145.6, 141.7, 137.4, 131.5, 127.9, 127.7, 124.0, 122.3, 119.5, 119.3, 54.2, 39.8; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.00; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 12 H 12 N +170.0964; Found 170.0964.

[0184] Example 30, Synthesis of

[0185] General synthetic process II was adopted. The reaction solution was stirred at 60 °C for 12 h. After post-treatment, 101.1 mg of the benzoyl-protected product was obtained. Appearance: white solid. Isolated yield: 74%. Melting point: 195 - 197 °C; 1 H NMR (400 MHz, CDCl3): δ (ppm) 7.76 - 7.65 (m, 3H), 7.61 (d, J = 8.2 Hz, 1H), 7.48 - 7.41 (m, 3H), 7.39 - 7.32 (m, 2H), 7.27 (d, J = 6.8 Hz, 1H), 7.19 (s, 1H), 6.48 (d, J = 8.1 Hz, 1H), 6.17 - 5.99 (m, 1H), 3.98 (dd, J = 17.8 Hz, 7.9 Hz, 1H), 3.18 (dd, J = 17.8 Hz, 3.2 Hz, 1H); 13 C NMR (100 MHz, CDCl3): δ (ppm) 167.1, 144.2, 142.1, 137.9, 134.3, 131.7, 131.3, 128.6, 128.4, 128.1, 127.0, 124.8, 122.9, 120.2, 120.0, 53.3, 40.5; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 19 H 15 NNaO + 296.1046; Found 296.1051.

[0186] Example 31, Synthesis of

[0187] General synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 117.8 mg of the primary amine salt was obtained. Appearance: brown solid. Isolated yield: 83%. Melting point: 172 - 174 °C; 11H NMR (400 MHz, CD3OD): δ (ppm) 7.52 (d, J = 7.5 Hz, 1H), 7.36 (t, J = 8.1 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 6.93 (d, J = 8.1 Hz, 1H), 5.03 (dd, J = 7.6 Hz, 2.7 Hz, 1H), 4.92 (s, 3H, NH3), 4.69 (dd, J = 11.3 Hz, 7.6 Hz, 1H), 4.55 (dd, J = 11.3 Hz, 2.7 Hz, 1H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 160.7, 131.5, 125.5, 122.4, 121.2, 120.4 (d, J = 318.3 Hz), 110.4, 73.8, 52.4; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.09; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C8H 10 NO + 136.0757; Found 136.0758.

[0188] Example 32, Synthesis of

[0189] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 16 h. After post-treatment, 106.2 mg of the primary amine salt was obtained. Appearance: white solid, isolation yield: 71%. Melting point: 169 - 171 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.35 (d, J = 7.8 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 6.95 (t, J = 7.6 Hz, 1H), 6.83 (d, J = 7.8 Hz, 1H), 4.95 (s, 3H, NH3), 4.39 (t, J = 5.3 Hz, 1H), 4.25 (dd, J = 6.8 Hz, 4.2 Hz, 2H), 2.40 - 2.21 (m, 1H), 2.16 - 2.01 (m, 1H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 154.9, 129.7, 128.7, 120.6, 120.4 (q, J = 318.6 Hz), 119.9, 117.1, 61.6, 44.6, 27.8; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.04; HRMS (ESI-TOF) m / z: [M-TfO] +Calcd for C9H 12 NO + 150.0913; Found 150.0908.

[0190] Example 33, Synthesis

[0191] The general synthetic process I was adopted. The reaction solution was stirred at 60 °C for 24 h, and the crude product was obtained after post-treatment. It was dissolved in 5 mL of dichloromethane, and trifluoromethanesulfonic acid (48 μL, 0.6 mmol) was added dropwise under ice bath conditions. After stirring at room temperature for one hour, the solvent was removed by rotary evaporation under reduced pressure, and column chromatography purification was carried out to obtain 142.3 mg of primary amine. Appearance: colorless liquid, isolation yield: 71%; 1 HNMR(400MHz, CD3OD): δ(ppm)7.54 - 7.27(m, 6H), 7.16(t, J = 7.6Hz, 1H), 7.01(t, J = 7.8Hz, 1H), 6.86(d, J = 8.2Hz, 1H), 4.90(s, 3H, NH3), 4.47 - 4.32(m, 1H), 4.10 - 3.98(m, 1H), 3.98 - 3.79(m, 1H), 2.51 - 2.31(m, 1H), 2.00 - 1.86(m, 1H); 13 C NMR(100MHz, CD3OD): δ(ppm)171.1, 138.2, 135.8, 130.4, 130.1, 128.13, 128.10, 127.3, 126.6, 125.3, 125.1, 120.4(q, J = 318.7Hz), 47.0, 42.1, 30.6; 19 F NMR(376MHz, CD3OD): δ(ppm)-80.02; HRMS(ESI-TOF) m / z: [M-TfO] + Calcd for C 16 H 17 N2O + 253.1335; Found 253.1344.

[0192] Example 34, Synthesis

[0193] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and 85.9 mg of primary amine salt was obtained after post-treatment. Appearance: semi-solid, isolation yield: 53%; 11H NMR (400 MHz, CD3OD): δ (ppm) 8.12 (d, J = 8.5 Hz, 1H), 7.92 (d, J = 8.5 Hz, 1H), 7.87 (d, J = 8.2 Hz, 1H), 7.73 - 7.46 (m, 4H), 5.20 (q, J = 6.7 Hz, 1H), 4.92 (s, 3H, NH3), 1.66 (d, J = 6.7 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 137.3, 134.1, 130.2, 128.8, 128.4, 126.5, 125.7, 125.1, 122.0, 121.8, 120.4 (d, J = 318.4 Hz), 46.0, 21.1; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.04; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 12 H 14 N + 172.1121; Found 172.1123.

[0194] Example 35, Synthesis of

[0195] Using General Synthesis Process II. The reaction solution was stirred at 25 °C for 12 h. After workup, 87.8 mg of the benzoyl-protected product was obtained. Appearance: white solid. Isolated yield: 64%. Melting point: 164 - 166 °C; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 8.14 (d, J = 8.1 Hz, 1H), 7.87 - 7.82 (m, 1H), 7.79 (d, J = 8.2 Hz, 1H), 7.71 (d, J = 7.6 Hz, 2H), 7.57 (d, J = 7.2 Hz, 1H), 7.53 - 7.39 (m, 4H), 7.33 (t, J = 7.6 Hz, 2H), 6.51 (d, J = 8.0 Hz, 1H), 6.16 - 6.03 (m, 1H), 1.74 (d, J = 6.8 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.5, 138.3, 134.5, 134.0, 131.5, 131.3, 128.8, 128.54, 128.51, 127.0, 126.7, 125.9, 125.3, 123.5, 122.7, 45.3, 20.7; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C19 H 17 NNaO + 298.1202; Found 298.1208.

[0196] Example 36, Synthesis

[0197] General synthetic process 1 was adopted. The reaction solution was stirred at 25 °C for 24 h, and after post-treatment, 101.8 mg of primary amine salt was obtained. Appearance: brown liquid, isolation yield: 73%; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.47 (dd, J = 5.1 Hz, 1.2 Hz, 1H), 7.21 (d, J = 3.6 Hz, 1H), 7.07 (dd, J = 5.1 Hz, 3.6 Hz, 1H), 4.89 (s, 3H, NH3), 4.74 (q, J = 6.8 Hz, 1H), 1.68 (d, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 140.3, 127.0, 126.5, 126.2, 46.2, 19.7; 19 F NMR (376 MHz, CD3OD): δ (ppm) -80.03; HRMS (ESI-TOF) m / z: [M - TfOH + Na] + Calcd for C6H9NNaS + 150.0348; Found 150.0340.

[0198] Example 37, Synthesis

[0199] General synthetic process 1 was adopted. The reaction solution was stirred at 25 °C for 12 h, and after post-treatment, 84.2 mg of primary amine salt was obtained. Appearance: semi-solid, isolation yield: 54%; 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.57 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.29 (t, J = 8.2 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 6.79 (s, 1H), 4.96 (s, 3H, NH3), 4.47 (q, J = 6.8 Hz, 1H), 1.63 (d, J = 6.8 Hz, 3H); 1313C NMR (100 MHz, CD3OD): δ (ppm) 157.0, 155.0, 128.0, 124.3, 122.8, 121.0, 120.4 (q, J = 318.5 Hz), 110.6, 103.0, 44.8, 18.0; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -79.99; HRMS (ESI-TOF) m / z: [M - TfOH + Na] + Calcd for C 10 H 11 NNaO + 184.0733; Found 184.0724.

[0200] Example 38, Synthesis of

[0201] Using general synthetic process II. The reaction solution was stirred at 25 °C for 12 h. After work-up, 82.0 mg of the benzoyl-protected product was obtained. Appearance: white solid. Isolated yield: 62%. Melting point: 131 - 133 °C; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.82 - 7.76 (m, 2H), 7.54 - 7.35 (m, 5H), 7.28 - 7.15 (m, 2H), 6.69 (d, J = 8.4 Hz, 1H), 6.59 (s, 1H), 5.62 - 5.45 (m, 1H), 1.65 (d, J = 6.9 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.7, 158.0, 154.8, 134.2, 131.7, 128.6, 128.2, 127.1, 124.2, 122.9, 121.0, 111.2, 102.7, 43.8, 19.7; HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 17 H 15 NNaO2 + 288.0995; Found 288.0998.

[0202] Example 39, Synthesis of

[0203] Using general synthetic process I. The reaction solution was stirred at 25 °C for 12 h. After work-up, 121.7 mg of the primary amine salt was obtained. Appearance: semi-solid. Isolated yield: 85%, 11:1 r.r. (a:b); 11H NMR (400 MHz, CD3OD): δ (ppm) 7.33 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 4.97 (s, 3H, NH3), 4.41 (q, J = 6.9 Hz, 1H), 2.35 (s, 3H), 1.60 (d, J = 6.9 Hz, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 138.9, 135.2, 129.5, 126.2, 120.4 (q, J = 318.4 Hz), 50.8, 19.8, 19.3; 19 19F NMR (376 MHz, CD3OD) δ (ppm) -80.10; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C9H 14 N + 136.1121; Found 136.1126.

[0204] Example 40, Synthesis of

[0205] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After work-up, 110.9 mg of the primary amine salt was obtained. Appearance: semi-solid, isolation yield: 78%; 11:1 r.r. (a:b); 1 1H NMR (400 MHz, CD3CN): δ (ppm) 7.40 - 7.21 (m, 4H), 5.91 (s, 3H, NH3), 4.49 (q, J = 6.8 Hz, 1H), 2.39 (s, 3H), 1.63 (d, J = 6.8 Hz, 3H); 13 13C NMR (100 MHz, CD3CN): δ (ppm) 139.5, 138.1, 130.4, 129.5, 128.1, 124.4, 121.3 (q, J = 319.7 Hz), 52.7, 21.0, 20.0; 19 19F NMR (376 MHz, CD3CN) δ (ppm) -79.35; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C9H 14 N + 136.1121; Found 136.1124.

[0206] Example 41, Synthesis of

[0207] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and after post-treatment, 98.8 mg of the primary amine salt was obtained. Appearance: semi-solid, isolation yield: 66%, >19:1 r.r. (a:b); 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.28 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 4.82 (s, 3H, NH3), 2.24 (s, 3H), 1.59 (s, 6H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 139.3, 138.0, 129.2, 124.2, 120.4 (q, J = 318.6 Hz), 55.2, 27.1, 19.6; 19 F NMR (376 MHz, CD3OD): δ (ppm) -80.09; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 10 H 16 N + 150.1277; Found 150.1275.

[0208] Example 42, Synthesis of

[0209] The general synthetic process I was adopted. The reaction solution was stirred at 25 °C for 16 h, and after post-treatment, 152.3 mg of the primary amine salt was obtained. Appearance: white solid, isolation yield: 85%. Melting point: 232 - 234 °C; 7:1 r.r. (a:b); 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.74 - 7.56 (m, 3H), 7.54 - 7.48 (m, 1H), 7.33 (t, J = 7.6 Hz, 1H), 7.26 (t, J = 7.4 Hz, 1H), 7.19 (d, J = 7.8 Hz, 1H), 4.88 (s, 3H, NH3), 4.76 (s, 1H), 2.70 (q, J = 7.6 Hz, 2H), 1.27 (t, J = 7.6 Hz, 3H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 147.4, 147.0, 143.9, 140.2, 137.7, 127.8, 127.5, 126.7, 124.2, 123.8, 119.3, 119.1, 56.9, 28.7, 15.0; 19 F NMR (376 MHz, CD3OD) δ (ppm) -80.01; HRMS (ESI-TOF) m / z: [M-TfO] +Calcd for C 15 H 16 N + 210.1277; Found 210.1273.

[0210] Example 43, Synthesis of

[0211] Using general synthetic process II. The reaction solution was stirred at 60 °C for 120 h. After post-treatment, 78.4 mg of the benzoyl-protected product was obtained. Appearance: white solid. Isolated yield: 44% (total isolated yield of regioisomers). Melting point: 181 - 183 °C; 3:1 r.r. (a:b); Mixture of regioisomers: 1 H NMR (400 MHz, CDCl3): δ (ppm) 7.73 - 7.67 (m, 2.6H), 7.5 - 7.54 (m, 0.6H), 7.52 - 7.45 (m, 3.3H), 7.44 - 7.33 (m, 3.3H), 7.24 - 7.12 (m, 4.0H), 6.96 (d, J = 8.3 Hz, 0.6H), 6.8 - 6.77 (m, 2.6H), 5.41 - 5.29 (m, 1.3H), 3.83 - 3.70 (m, 4.0H), 3.38 (dd, J = 13.4, 6.5 Hz, 1.0H), 3.24 - 3.06 (m, 1.6H); 13 C NMR (100 MHz, CDCl3): δ (ppm) 167.0, 166.9, 159.2, 158.7, 147.4, 143.4, 134.3, 133.9, 132.4, 132.1, 131.9, 131.7, 130.24, 130.17, 128.69, 128.65, 128.0, 127.4, 127.0, 126.9, 118.9, 118.8, 114.24, 114.16, 111.1, 110.4, 55.31, 55.25, 54.8, 54.6, 42.4, 41.5; HRMS (ESI-TOF) m / z: [M+Na] + Calcd forC 23 H 20 N2NaO2 + 379.1417; Found 379.1425.

[0212] Example 44, Synthesis of

[0213] Using general synthetic process I. The reaction solution was stirred at 25 °C for 24 h. After post-treatment, 36.0 mg of the primary amine salt was obtained. Appearance: yellow liquid. Isolated yield: 26%;1 1H NMR (400 MHz, CD3CN): δ (ppm) 5.92 - 5.79 (m, 1H), 5.42 - 5.31 (m, 1H), 4.54 (brs, 3H, NH3), 3.67 - 3.55 (m, 1H), 2.13 - 1.99 (m, 2H), 1.79 - 1.68 (m, 1H), 1.68 - 1.52 (m, 1H), 1.48 - 1.35 (m, 2H), 0.96 - 0.82 (m, 6H); 13 13C NMR (100 MHz, CD3CN): δ (ppm) 139.0, 125.4, 121.5 (q, J = 320.0 Hz), 56.8, 34.5, 26.4, 22.2, 13.4, 9.7; 19 19F NMR (376 MHz, CD3CN): δ (ppm) -78.60; HRMS (ESI-TOF) m / z: [M - TfOH + Na] + Calcd for C8H 17 NNa + 150.1253; Found 150.1261.

[0214] Example 45, Synthesis of

[0215] Using General Synthesis Process II. The reaction solution was stirred at 25 °C for 24 h. After work-up, 36.0 mg of the benzoyl-protected product was obtained. Appearance: semi-solid. Isolated yield: 31%; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.84 - 7.70 (m, 2H), 7.61 - 7.36 (m, 3H), 5.98 (d, J = 8.5 Hz, 1H), 5.78 - 5.59 (m, 1H), 5.50 - 5.32 (m, 1H), 4.56 (q, J = 7.1 Hz, 1H), 2.02 (q, J = 7.1 Hz, 2H), 1.70 - 1.63 (m, 2H), 1.44 - 1.35 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H), 0.89 (t, J = 7.4 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.7, 135.0, 132.1, 131.3, 129.9, 128.6, 126.9, 52.7, 34.4, 28.4, 22.3, 13.7, 10.3; HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 15 H 21 NNaO+ 254.1515; Found 254.1524.

[0216] Example 46, Synthesis

[0217] Using general synthesis process II. The reaction solution was stirred at 40 °C for 24 h. After post-treatment, 62.0 mg of the benzoyl-protected product was obtained. Appearance: white solid, isolation yield: 45%. Melting point: 135 - 137 °C; 9:1 r.r. (a:b); 1 H NMR (400 MHz, CDCl3): δ (ppm) 7.79 - 7.67 (m, 2H), 7.46 - 7.39 (m, 1H), 7.34 (dd, J = 8.5, 6.9 Hz, 4H), 7.25 (dd, J = 8.5, 6.5 Hz, 2H), 7.22 - 7.17 (m, 1H), 6.15 (d, J = 8.2 Hz, 1H), 5.99 (s, 1H), 4.92 - 4.77 (m, 1H), 2.49 - 2.30 (m, 2H), 2.06 - 1.97 (m, 1H), 1.83 - 1.74 (m, 2H), 1.6 - 1.58 (m, 1H); 13 C NMR (100 MHz, CDCl3): δ (ppm) 166.8, 141.2, 140.7, 134.8, 131.4, 128.6, 128.4, 127.5, 126.9, 125.3, 124.4, 46.0, 29.2, 27.3, 20.4; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 19 H 19 NNaO + 300.1359; Found 300.1350. C 19 H 19 NNaO + 300.1359; Found 300.1350.

[0218] Example 47, Synthesis

[0219] Using general synthesis process I. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 97.4 mg of the primary amine salt was obtained. Appearance: white solid, isolation yield: 65%. Melting point: 158 - 160 °C; 1 H NMR (400 MHz, CD3OD): δ (ppm) 4.88 (s, 3H, NH3), 3.58 (t, J = 5.4 Hz, 1H), 2.18 - 1.83 (m, 7H), 1.82 - 1.51 (m, 7H);13 C NMR (100 MHz, CD3OD): δ (ppm) 136.9, 123.5, 120.4 (q, J = 318.4 Hz), 50.4, 30.1, 29.6, 27.7, 26.5, 22.4, 22.1, 17.9; 19 F NMR (376 MHz, CD3OD): δ (ppm) -80.10; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 10 H18N + 152.1434; Found 152.1430.

[0220] Example 48, Synthesis of

[0221] Using general synthetic process II. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 12.9 mg of the benzoyl-protected product was obtained. Appearance: semi-solid, isolation yield: 11%; 1 H NMR (400 MHz, CD3CN): δ (ppm) 7.76 - 7.68 (m, 2H), 7.58 - 7.51 (m, 3H), 7.48 - 7.37 (m, 5H), 6.53 (d, J = 8.3 Hz, 1H), 6.18 (dd, J = 8.4, 2.5 Hz, 1H), 2.47 (d, J = 2.5 Hz, 1H). (The yield of this compound is relatively low and is only characterized by 1 H NMR and is consistent with the data reported in the existing literature)

[0222] Example 49, Synthesis of

[0223] Using general synthetic process II. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 25.2 mg of the benzoyl-protected product was obtained. Appearance: white solid, isolation yield: 27%. Melting point: 137 - 139 °C; 1 H NMR (400 MHz, CDCl3): δ (ppm) 7.79 - 7.70 (m, 2H), 7.50 - 7.43 (m, 1H), 7.43 - 7.35 (m, 2H), 6.24 (brs, 1H), 4.39 (q, J = 7.0 Hz, 1H), 2.17 - 1.96 (m, 2H), 1.78 - 1.58 (m, 4H), 1.54 - 1.36 (m, 2H); 1313C NMR (100 MHz, CDCl3): δ (ppm) 167.2, 134.9, 131.2, 128.5, 126.9, 51.7, 33.2, 23.8; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 12 H 15 NNaO + 212.1046; Found 212.1044.

[0224] Example 50, Synthesis of

[0225] Using general synthetic process II. The reaction solution was stirred at 25 °C for 12 h, and after work-up, 9.1 mg of the benzoyl-protected product was obtained. Appearance: semi-solid, isolation yield: 9%; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.74 (d, 2H), 7.5 - 7.36 (m, 3H), 5.97 (s, 1H), 4.07 - 3.89 (m, 1H), 2.11 - 1.95 (m, 2H), 1.81 - 1.71 (m, 2H), 1.71 - 1.59 (m, 2H), 1.52 - 1.33 (m, 2H), 1.31 - 1.21 (m, 2H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.6, 135.1, 131.2, 128.5, 126.8, 48.7, 33.3, 25.6, 24.9; HRMS (ESI-TOF) m / z: [M+Na] + Calcd forC 13 H 17 NNaO + 226.1202; Found 226.1208.

[0226] Example 51, Synthesis of

[0227] Using general synthetic process II. The reaction solution was stirred at 25 °C for 16 h, and after work-up, 30.5 mg of the benzoyl-protected product was obtained. Appearance: white solid, isolation yield: 28%. Melting point: 94 - 96 °C; >10:1 r.r. (a:b); 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.80 - 7.64 (m, 2H), 7.54 - 7.35 (m, 3H), 5.83 (brs, 1H), 2.25 - 2.00 (m, 2H), 1.65 - 1.54 (m, 6H), 1.50 - 1.44 (m, 5H);13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.9, 136.2, 131.1, 128.5, 126.7, 53.7, 36.8, 26.5, 25.6, 22.2; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 14 H 19 NNaO + 240.1359; Found 240.1368.

[0228] Example 52, Synthesis of

[0229] General synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and after post-treatment, 100.1 mg of the primary amine salt was obtained. Property: white solid, isolation yield: 76%. Melting point: 206 - 208 °C; 1 1H NMR (400 MHz, CD3CN): δ (ppm) 6.38 (s, 3H, NH3), 3.39 - 3.27 (m, 1H), 2.04 - 1.95 (m, 2H), 1.78 - 1.66 (m, 2H), 1.66 - 1.35 (m, 8H); 13 13C NMR (100 MHz, CD3CN): δ (ppm) 54.3, 32.7, 27.8, 23.8; 19 19F NMR (376 MHz, CD3CN) δ (ppm) -79.41; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C7H 16 N + 114.1277; Found 114.1284.

[0230] Example 53, Synthesis of

[0231] General synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h, and after post-treatment, 98.2 mg of the primary amine salt was obtained. Property: white solid, isolation yield: 71%. Melting point: 201 - 203 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 4.90 (s, 3H, NH3), 3.36 - 3.31 (m, 1H), 2.03 - 1.85 (m, 2H), 1.85 - 1.41 (m, 12H); 1313C NMR (100 MHz, CD3OD): δ (ppm) 120.4 (d, J = 318.4 Hz), 51.7, 30.5, 26.1, 25.2, 23.1; 19 19F NMR (376 MHz, CD3OD) δ (ppm) -80.10; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C8H 18 N + 128.1434; Found 128.1433.

[0232] Example 54, Synthesis

[0233] The general synthetic process I was adopted. The reaction solution was stirred at 40 °C for 24 h. After post-treatment, 95.0 mg of the primary amine salt was obtained. Appearance: white solid. Isolated yield: 57%. Melting point: 197 - 199 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 4.88 (s, 3H, NH3), 3.30 - 3.24 (m, 1H), 1.88 - 1.69 (m, 2H), 1.64 - 1.22 (m, 20H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 120.4 (d, J = 318.4 Hz), 49.0, 27.7, 23.7, 23.5, 22.8, 22.7, 20.2; 19 19F NMR (376 MHz, CD3OD) δ (ppm) -80.11; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 12 H 26 N + 184.2060; Found 184.2065.

[0234] Example 55, Synthesis

[0235] The general synthetic process II was adopted. The reaction solution was stirred at 40 °C for 24 h. After post-treatment, 113.4 mg of the benzoyl-protected product was obtained. Appearance: white solid. Isolated yield: 79%. Melting point: 182 - 184 °C; 11H NMR (400 MHz, CDCl3): δ (ppm) 7.75 (d, J = 7.4 Hz, 2H), 7.55 - 7.35 (m, 3H), 5.89 (brs, 1H), 4.30 (d, J = 10.1 Hz, 1H), 1.86 - 1.58 (m, 3H), 1.59 - 1.10 (m, 19H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.7, 135.1, 131.3, 128.5, 126.8, 46.6, 30.4, 24.0, 23.8, 23.5, 23.4, 21.5; HRMS (ESI - TOF) m / z: [M + Na] + Calcd for C 19 H 29 NNaO + 310.2141; Found 310.2150.

[0236] Example 56, Synthesis of

[0237] The general synthetic process I was adopted. The reaction solution was stirred at 60 °C for 16 h. After work-up, 110.8 mg of the primary amine salt was obtained. Appearance: white solid. Isolated yield: 59%. Melting point: 208 - 210 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 4.95 (s, 3H, NH3), 3.23 - 3.16 (m, 1H), 1.75 - 1.54 (m, 6H), 1.50 - 1.36 (m, 22H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 120.4 (d, J = 318.3 Hz), 50.6, 30.7, 26.6, 26.45, 26.40, 26.3, 26.2, 22.7; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.09; HRMS (ESI - TOF) m / z: [M - TfO] + Calcd for C 15 H 32 N + 226.2529; Found 226.2537.

[0238] Example 57, Synthesis of

[0239] The general synthetic process II was adopted. The reaction solution was stirred at 80 °C for 48 h. After work-up, 12.8 mg of the benzoyl-protected product was obtained. Appearance: white solid. Isolated yield: 10%.1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.77 - 7.66 (m, 2H), 7.50 - 7.37 (m, 3H), 5.80 (s, 1H), 2.13 (s, 9H), 1.77 - 1.67 (m, 6H). (The yield of this compound is relatively low and is characterized only by 1 1H NMR and is consistent with the data reported in the existing literature.)

[0240] Example 58, Synthesis

[0241] Using General Synthetic Process II. Iron octachlorophthalocyanine (5 mol%) as the catalyst, compound 1 (10.0 mmol), acetonitrile solvent (4 mL), and an aqueous solution (36 mL) of nitrogen source 2 (0.5 mmol) were successively added to a dry round-bottom flask. The reaction mixture was stirred at 40 °C for 16 h. After work-up, 21.6 mg of the benzoyl-protected product was obtained. Appearance: white solid. Isolated yield: 21%. Melting point: 67 - 69 °C; 5:1 r.r. (a:b); 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.77 - 7.65 (m, 2H), 7.52 - 7.37 (m, 3H), 5.71 (s, 1H), 2.02 - 1.87 (m, 2H), 1.79 - 1.72 (m, 2H), 1.34 (s, 3H), 0.89 (t, J = 7.5 Hz, 6H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.9, 136.1, 131.1, 128.5, 126.7, 57.2, 30.5, 23.5, 8.1; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 13 H 19 NNaO + 228.1359; Found 228.1365.

[0242] Example 59, Synthesis

[0243] Using general synthetic process II. In a dry round-bottom flask, successively add the catalyst iron octachlorophthalocyanine (5 mol%), compound 1 (10.0 mmol), acetonitrile solvent (4 mL), and an aqueous solution (36 mL) of nitrogen source 2 (0.5 mmol). The reaction solution is stirred at 40 °C for 16 h. After work-up, 12.3 mg of the benzoyl-protected product is obtained. Appearance: white solid. Isolated yield: 12% (total isolated yield of regioisomers). Melting point: 135 - 137 °C; 2:1 r.r. (a:b); regioisomer mixture: 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.74 - 7.61 (m, 3H), 7.49 - 7.30 (m, 4.5H), 5.82 (d, J = 8.3 Hz, 1H), 5.74 (d, J = 8.9 Hz, 0.5H), 4.19 - 4.09 (m, 1H), 4.08 - 3.97 (m, 0.5H), 1.53 - 1.25 (m, 9H), 1.17 (d, J = 6.6 Hz, 3H), 0.93 - 0.67 (m, 6H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 167.3, 166.8, 135.2, 135.1, 131.3, 128.56, 128.54, 126.8, 50.9, 45.8, 37.1, 36.8, 28.3, 28.1, 22.6, 21.1, 19.2, 14.08, 14.03, 10.3; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 13 H 19 NNaO + 228.1359; Found 228.1363.

[0244] Example 60, Synthesis of

[0245] Using general synthetic process II. In a dry round-bottom flask, successively add the catalyst iron octachlorophthalocyanine (5 mol%), compound 1 (10.0 mmol), acetonitrile solvent (4 mL), and an aqueous solution (36 mL) of nitrogen source 2 (0.5 mmol). The reaction solution is stirred at 40 °C for 16 h. After work-up, 14.3 mg of a mixed product of benzoyl-protected regioisomers is obtained. Appearance: white solid. Isolated yield: 13% (total isolated yield of regioisomers). Melting point: 82 - 84 °C; 2:1 r.r. (a:b); Although the regioisomer mixture cannot be completely separated, a part of the pure product can be obtained by purification through column chromatography; isomer a: 11H NMR (400 MHz, CDCl3): δ (ppm) 7.75 (d, J = 7.5 Hz, 2H), 7.49 (t, J = 7.2 Hz, 1H), 7.43 (t, J = 7.4 Hz, 2H), 5.87 (d, J = 8.2 Hz, 1H), 4.26 - 4.12 (m, 1H), 1.57 - 1.50 (m, 2H), 1.41 - 1.29 (m, 6H), 1.25 - 1.18 (m, 3H), 0.93 - 0.86 (m, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.8, 135.1, 131.3, 128.6, 126.8, 45.8, 37.1, 31.7, 25.8, 22.6, 21.1, 14.0; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 14 H 21 NNaO + 242.1515; Found 242.1514; Isomer b: 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.78 - 7.72 (m, 2H), 7.52 - 7.41 (m, 3H), 5.80 (d, J = 9.0 Hz, 1H), 4.14 - 3.98 (m, 1H), 1.68 - 1.49 (m, 4H), 1.40 - 1.32 (m, 4H), 1.00 - 0.88 (m, 6H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 167.2, 135.2, 131.3, 128.6, 126.8, 51.1, 34.6, 28.15, 28.10, 22.7, 14.0, 10.3. HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 14 H 21 NNaO + 242.1515; Found 242.1513.

[0246] Example 61, Synthesis of

[0247] Using General Synthetic Procedure II. The reaction solution was stirred at 25 °C for 12 h. After work-up, 23.5 mg of the benzoyl-protected product was obtained. Appearance: white solid, isolation yield: 18%. Melting point: 70 - 72 °C; 11H NMR (400 MHz, CDCl3): δ (ppm) 7.77 - 7.64 (m, 2H), 7.52 - 7.36 (m, 3H), 5.83 (s, 1H), 1.84 - 1.74 (m, 2H), 1.59 - 1.54 (m, 2H), 1.43 (s, 6H), 1.33 - 1.25 (m, 8H), 0.91 - 0.82 (m, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 166.8, 136.1, 131.1, 128.5, 126.7, 54.2, 40.5, 31.9, 30.0, 29.3, 27.0, 24.2, 22.7, 14.1; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 17 H 27 NNaO + 284.1985; Found 284.1988.

[0248] General synthetic process three:

[0249]

[0250] In a dry round-bottom flask, successively add supported catalyst iron octachlorophthalocyanine (5 mol%, supported on 1 g of silica), compound 1 (0.25 mmol), dioxane solvent (1 mL), and an aqueous solution (19 mL) of nitrogen source 2 (0.75 mmol). The reaction mixture is stirred at 20 - 100 °C for 12 - 24 h, monitored by TLC or GC-MS until compound 1 is completely consumed to form primary amine product 3. Then, the solvent is removed by rotary evaporation under reduced pressure, and column chromatography purification is carried out to obtain the primary amine product (in the form of trifluoromethanesulfonate).

[0251] Example 62, Synthesis of

[0252] The general synthetic process three is adopted. The reaction mixture is stirred at 80 °C for 12 h. After post-treatment, 82.1 mg of primary amine salt is obtained, appearance: semi-solid, isolated yield: 80%; 11H NMR (400 MHz, CDCl3): δ (ppm) 7.87 (d, J = 1.8 Hz, 1H), 7.46 (d, J = 1.7 Hz, 1H), 6.50 (brs, 3H), 4.97 (dd, J = 8.7 Hz, 5.1 Hz, 1H), 2.68 (s, 3H), 2.55 (dd, J = 14.5 Hz, 8.7 Hz, 1H), 2.24 (dd, J = 14.5 Hz, 5.1 Hz, 1H), 1.44 (s, 3H), 1.37 (s, 9H), 1.25 (s, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 203.7, 155.4, 154.5, 133.72, 133.69, 127.8, 125.4, 119.9 (q, J = 319.2 Hz), 55.0, 45.2, 43.2, 35.1, 31.2, 30.5, 30.0, 28.0; 19 19F NMR (376 MHz, CDCl3) δ (ppm) -78.62; HRMS (ESI-TOF) m / z: [M - TfO] + Calcd for C 17 H 26 N O + 260.2009; Found 260.2003.

[0253] Example 63, Synthesis of

[0254] Using the general synthetic process III. The reaction solution was stirred at 60 °C for 24 h. After work-up, the crude product was obtained, dissolved in 5 mL of dichloromethane, and trifluoromethanesulfonic acid (160 μL, 2.0 mmol) was added dropwise under ice bath conditions. After stirring at room temperature for one hour, the solvent was removed by rotary evaporation under reduced pressure, and column chromatography purification was carried out to obtain 77.3 mg of the primary amine. Appearance: white solid, isolation yield: 73%. Melting point: 152 - 154 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.64 (t, J = 8.3 Hz, 1H), 7.58 - 7.52 (m, 2H), 7.49 - 7.38 (m, 5H), 4.91 (s, 3H, NH3), 3.87 (s, 3H), 2.03 (s, 3H); 13¹³C NMR (100 MHz, CD₃OD): δ (ppm) 170.3, 159.7 (d, J = 248.9 Hz), 136.8 (d, J = 7.6 Hz), 134.4, 131.6 (d, J = 4.0 Hz), 130.5 (d, J = 13.6 Hz), 128.6 (d, J = 3.0 Hz), 128.3, 128.1, 121.8 (d, J = 3.7 Hz), 120.4 (d, J = 318.4 Hz), 113.7 (d, J = 25.9 Hz), 61.0, 53.2, 20.8; 19 ¹⁹F NMR (376 MHz, CD₃OD): δ (ppm) -80.06, -117.10--117.19 (m); HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 16 H 17 FNO₂ + 274.1238; Found 274.1245.

[0255] Example 64, Synthesis of

[0256] Using general synthetic procedure III. The reaction solution was stirred at 25 °C for 12 h. After workup, 73.1 mg of the primary amine salt of the regioisomer mixture was obtained. Appearance: semi-solid, isolation yield: 74% (total isolation yield of regioisomers); 1:1.5 r.r. (A / B); Although the regioisomer mixture could not be completely separated, a part of the pure primary amine product could be obtained by column chromatography purification; Isomer A: 1 ¹H NMR (400 MHz, CDCl₃): δ (ppm) 7.33 (d, J = 8.2 Hz, 2H), 7.16 (d, J = 8.2 Hz, 2H), 5.92 (brs, 3H), 3.74 (s, 3H), 2.45 (d, J = 7.2 Hz, 2H), 1.95 (s, 3H), 1.88 - 1.79 (m, 1H), 0.88 (d, J = 6.6 Hz, 6H); 13 ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 171.7, 143.2, 133.6, 129.9, 125.1, 62.3, 53.7, 44.9, 30.1, 22.5, 22.3; 19 ¹⁹F NMR (376 MHz, CDCl₃) δ (ppm) -78.59; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 14 H 22 NO₂+ 236.1645; Found 236.1642. Isomer B: 1 H NMR (400 MHz, CDCl3): δ (ppm) 7.32 - 7.18 (m, 4H), 3.72 (q, J = 7.1 Hz, 1H), 3.66 (s, 3H), 3.58 (d, J = 7.5 Hz, 1H), 2.72 (brs, 3H), 1.94 - 1.82 (m, J = 6.8 Hz, 1H), 1.49 (d, J = 7.2 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.76 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ (ppm) 175.1, 142.7, 139.3, 127.40, 127.37, 62.1, 52.0, 45.1, 34.9, 19.7, 18.9, 18.6; 19 F NMR (376 MHz, CDCl3) δ (ppm) -78.48; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 14 H 22 NO2 + 236.1645; Found 236.1642.

[0257] Example 65, was synthesized using General Synthetic Procedure III. The reaction solution was stirred at 60 °C for 12 h. After work-up, 77.3 mg of the primary amine salt of the regioisomer mixture was obtained. Appearance: semi-solid. Isolation yield: 72% (total isolation yield of regioisomers); 2:1 r.r. (A / B); Although the regioisomer mixture could not be completely separated, a portion of the pure primary amine product could be obtained by purification through column chromatography; Isomer A: 1 H NMR (400 MHz, CD3OD): δ (ppm) 7.19 (d, J = 7.6 Hz, 1H), 6.86 (s, 1H), 6.80 (d, J = 7.6 Hz, 1H), 4.90 (s, 3H, NH3), 4.12 - 3.97 (m, 4H), 3.65 (s, 3H), 2.34 (s, 3H), 1.84 - 1.70 (m, 4H), 1.22 (s, 6H); 13 C NMR (100 MHz, CD3OD): δ (ppm) 178.6, 156.9, 141.1, 130.0, 121.0, 120.4 (q, J = 318.4 Hz), 118.8, 112.1, 67.8, 51.0, 41.9, 39.0, 36.6, 24.7, 24.2, 20.3;19 19F NMR (376 MHz, CD3OD) δ (ppm) -80.05; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 16 H 26 NO3 + 280.1907; Found 280.1909. Isomer B: 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.13 (d, J = 7.5 Hz, 1H), 6.91 (d, J = 1.6 Hz, 1H), 6.85 (dd, J = 7.5 Hz, 1.6 Hz, 1H), 4.92 (s, 3H, NH3), 3.98 (t, J = 3.0 Hz, 2H), 3.94 (s, 2H), 3.64 (s, 3H), 2.19 (s, 3H), 1.76 - 1.70 (m, 4H), 1.21 (s, 6H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 178.5, 157.5, 131.6, 130.7, 127.5, 120.4 (q, J = 318.5 Hz), 120.3, 111.0, 67.8, 50.9, 43.0, 41.8, 36.9, 24.8, 24.2, 14.7; 19 19F NMR (376 MHz, CD3OD) δ (ppm) -80.12; HRMS (ESI-TOF) m / z: [M-TfOH + Na] + Calcd for C 16 H 25 NNaO3 + 302.1727; Found 302.1732.

[0258] Example 66, Synthesis of

[0259] Using general synthetic process III. The reaction solution was stirred at 60 °C for 24 h. After work-up, 76.0 mg of the primary amine salt was obtained. Appearance: colorless liquid. Isolated yield: 63% (total isolated yield of diastereoisomers); dr = 3.7:1; Diastereoisomer mixture: 11H NMR (400 MHz, CDCl3): δ (ppm) 7.31 (d, J = 2.0 Hz, 0.3H), 7.22 (d, J = 2.0 Hz, 1H), 7.20 - 7.05 (m, 2.6H), 4.55 (brs, 3.8H), 4.34 (d, J = 5.1 Hz, 1H), 4.19 (dd, J = 10.3 Hz, 7.6 Hz, 0.3H), 3.64 (s, 0.8H), 3.27 (s, 3H), 2.99 - 2.77 (m, 1.3H), 2.41 (d, J = 12.8 Hz, 1H), 2.34 - 2.23 (m, 1.6H), 2.14 (td, J = 13.7 Hz, 5.3 Hz, 1H), 1.89 - 1.48 (m, 8H), 1.33 - 0.93 (m, 16H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 179.5, 178.9, 147.3, 146.9, 146.8, 146.6, 137.0, 133.6, 127.9, 126.8, 125.5, 125.2, 124.6, 124.4, 120.1 (q, J = 318.8 Hz), 52.2, 52.1, 51.7, 50.2, 47.3, 47.0, 43.8, 39.4, 38.1, 37.7, 37.5, 37.4, 37.1, 36.5, 33.7, 33.5, 32.3, 28.6, 25.5, 24.4, 24.0, 23.85, 23.83, 23.79, 18.49, 18.45, 16.4, 16.2; 19 19F NMR (376 MHz, CDCl3) δ (ppm) -78.38; HRMS (ESI-TOF) m / z: [M - TfO] + Calcd for C 21 H 32 NO2 + 330.2428; Found 330.2435.

[0260] Example 67, Synthesis of

[0261] Using general synthetic process III. The reaction solution was stirred at 25 °C for 12 h. After work-up, 61.0 mg of the primary amine salt was obtained. Appearance: semi-solid, isolation yield: 40% (total isolation yield of isomers); 2.6:1 r.r. (A / B); Although the regioisomer mixture could not be completely separated, a part of the pure primary amine product could be obtained by purification through column chromatography. Isomer A: At 1Compound A was observed as a mixture of diastereoisomers in ¹H NMR, but it was difficult to calculate the exact ratio. Therefore, HPLC analysis was performed to determine the exact diastereoisomer ratio [Daicel chiralpak IC, acetonitrile / water (0.1% phosphoric acid) = 45 / 55, 1.0 mL / min, λ = 220 nm, t (main peak) = 22.299 min, t (sub-peak) = 25.112 min), isomer A: dr = 1.3:1; mixture of diastereoisomers: 1 ¹H NMR (400 MHz, CDCl₃): δ (ppm) 4.20 - 4.02 (m, 1H), 3.65 (s, 3H), 2.32 (d, J = 2.8 Hz, 3H), 2.18 (s, 3H), 2.14 - 2.04 (m, 4H), 2.01 - 1.75 (m, 4H), 1.55 - 1.46 (m, 2H), 1.40 - 1.06 (m, 22H), 0.89 - 0.82 (m, 12H); 13 ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 150.5, 150.4, 147.3, 147.1, 129.3, 129.2, 125.95, 125.91, 123.85, 123.80, 123.2, 122.9, 76.1, 75.7, 60.19, 60.17, 43.9, 43.8, 42.70, 42.64, 42.21, 42.15, 41.64, 41.61, 40.6, 39.4, 37.6, 37.5, 37.43, 37.40, 37.38, 37.33, 37.31, 32.8, 32.73, 32.69, 32.67, 32.64, 27.9, 25.7, 24.83, 24.82, 24.48, 24.44, 23.7, 22.74, 22.65, 21.3, 21.1, 19.8, 19.72, 19.70, 19.64, 19.58, 12.74, 12.70, 12.4, 11.98, 11.95; 19 ¹⁹F NMR (376 MHz, CDCl₃) δ (ppm) -78.34; HRMS (ESI-TOF) m / z: [M - TfOH + Na] + Calcd for C 30 H 53 NNaO₂ + 482.3969; Found 482.3966. Isomer B: 11H NMR (400 MHz, CDCl3): δ (ppm) 4.08 (s, 2H), 3.61 (s, 3H), 3.54 (brs, 3H), 2.56 (t, J = 6.7 Hz, 2H), 2.27 (s, 3H), 2.15 (s, 3H), 1.92 - 1.74 (m, 2H), 1.61 - 1.47 (m, 3H), 1.37 - 1.09 (m, 21H), 0.88 - 0.80 (m, 12H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 150.0, 148.2, 130.3, 128.5, 119.5, 118.7, 60.4, 39.5, 39.4, 37.8, 37.47, 37.44, 37.40, 37.3, 32.8, 32.70, 32.67, 28.0, 24.8, 24.5, 24.0, 22.7, 22.6, 21.4, 20.3, 19.73, 19.66, 19.56, 19.50, 12.0, 11.8; 19 19F NMR (376 MHz, CDCl3) δ (ppm) -78.38; HRMS (ESI-TOF) m / z: [M - TfOH + Na] + Calcd for C 30 H 53 NNaO2 + 482.3969; Found 482.3970.

[0262] Example 68, Synthesis of

[0263] Using the general synthetic process III. In a dry round-bottom flask, successively add the supported catalyst iron octachlorophthalocyanine (5 mol%, supported on 1 g of silica), compound 1 (0.25 mmol), dioxane solvent (3 mL), and an aqueous solution (7 mL) of nitrogen source 2 (0.75 mmol). The reaction solution was stirred at 100 °C for 24 h. After work-up, 65.3 mg of the primary amine salt was obtained. Appearance: semi-solid, isolated yield: 56% (total isolated yield of diastereomers); dr = 1.2:1; diastereomer mixture: 11H NMR (400 MHz, CDCl3): δ (ppm) 7.25 - 7.12 (m, 1H), 6.99 - 6.85 (m, 1H), 6.84 - 6.72 (m, 1H), 4.77 (s, 3H, NH3), 4.28 - 4.16 (m, 1H), 3.74 (s, 3H), 3.36 (s, 3H), 3.33 - 3.24 (m, 1H), 2.33 - 1.91 (m, 6H), 1.57 - 1.25 (m, 7H), 0.83 - 0.70 (m, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 158.12, 158.06, 136.9, 135.8, 132.9, 132.5, 126.8, 126.7, 119.9 (q, J = 318.6 Hz), 115.0, 114.2, 113.5, 111.5, 90.6, 57.89, 57.86, 55.31, 55.30, 50.8, 49.7, 49.5, 49.4, 43.8, 43.7, 43.4, 43.0, 37.8, 37.7, 35.8, 33.7, 32.9, 27.7, 26.3, 25.9, 22.8, 22.6, 11.5, 11.4; 19 19F NMR (376 MHz, CDCl3) δ (ppm) -78.38; HRMS (ESI-TOF) m / z: [M - TfOH + Na] + Calcd for C 20 H 29 NNaO2 + 338.2091; Found 338.2094.

[0264] Example 69, Synthesis of

[0265] Using general synthetic process III. The reaction solution was stirred at 100 °C for 12 h. After work-up, 34.6 mg of the primary amine salt was obtained. Appearance: colorless liquid. Isolated yield: 30%; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.23 - 7.01 (m, 4H), 6.99 - 6.81 (m, 4H), 4.85 (brs, 3H), 3.99 (q, J = 6.7 Hz, 1H), 3.82 (s, 3H), 3.81 (s, 3H), 2.00 (q, J = 7.5 Hz, 2H), 1.10 (d, J = 6.7 Hz, 3H), 0.71 (t, J = 7.5 Hz, 3H); 1313C NMR (100 MHz, CDCl3): δ (ppm) 159.0, 158.6, 145.2, 135.2, 132.6, 131.3, 129.4, 127.9, 114.1, 113.9, 55.21, 55.19, 49.0, 29.2, 19.9, 12.5; 19 19F NMR (376 MHz, CDCl3) δ (ppm) -78.46; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 20 H 26 NO2 + 312.1958; Found 312.1949.

[0266] Example 70, Synthesis of

[0267] Using general synthetic procedure III. The reaction solution was stirred at 25 °C for 12 h. After work-up, 68.3 mg of the primary amine salt was obtained. Appearance: white solid. Isolated yield: 74% (total isolated yield of regioisomers); 2:1 r.r. (A / B); Although the regioisomer mixture could not be completely separated, a portion of the pure primary amine product could be obtained by purification by column chromatography. Isomer A: white solid; melting point: 185 - 187 °C; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.05 (brs, 3H, NH3), 5.44 - 5.31 (m, 1H), 3.63 (s, 1H), 2.14 - 2.03 (m, 1H), 1.99 - 1.79 (m, 3H), 1.75 (s, 3H), 1.73 - 1.64 (m, 2H), 1.61 - 1.41 (m, 3H), 0.99 (s, 3H), 0.98 - 0.88 (m, 6H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 149.3, 119.9 (d, J = 318.6 Hz), 115.4, 57.5, 55.6, 53.8, 53.5, 46.3, 36.5, 34.0, 33.9, 27.8, 25.5, 24.6, 23.3, 14.7; 19 19F NMR (376 MHz, CDCl3) δ (ppm) -78.41; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 15 H 26 N + 220.2060; Found 220.2070. Isomer B: yellow liquid; 11H NMR (400 MHz, CDCl3): δ (ppm) 6.86 (brs, 3H, NH3), 5.65 (t, J = 3.4 Hz, 1H), 3.60 - 3.31 (m, 2H), 2.23 (d, J = 17.5 Hz, 1H), 1.99 - 1.51 (m, 7H), 1.50 - 1.28 (m, 3H), 0.97 (d, J = 6.3 Hz, 6H), 0.84 (d, J = 7.1 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 135.7, 126.6, 58.9, 53.7, 51.2, 48.7, 45.7, 41.3, 40.0, 38.6, 36.0, 27.2, 25.1, 24.8, 15.3; 19 19F NMR (376 MHz, CDCl3) δ (ppm) -78.19; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 15 H 26 N + 220.2060; Found 220.2070.

[0268] Example 71, Synthesis

[0269] Using general synthetic process III. The reaction solution was stirred at 25 °C for 12 h. After work-up, 71.0 mg of the primary amine salt was obtained. Appearance: white solid, isolation yield: 94%; melting point: 98 - 100 °C; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 4.94 (brs, 3H), 2.44 - 2.31 (m, 1H), 2.09 - 1.78 (m, 6H), 1.43 (s, 3H), 1.35 (d, J = 11.0 Hz, 1H), 1.32 (s, 3H), 1.05 (s, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 120.4 (q, J = 318.5 Hz), 58.9, 50.9, 39.9, 38.6, 27.1, 26.5, 26.4, 26.3, 23.9, 22.5; 19 19F NMR (376 MHz, CD3OD) δ (ppm) -80.05; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 10 H 20 N + 154.1590; Found 154.1583.

[0270] Example 72 Synthesis of

[0271] General synthetic process I was adopted. The reaction solution was stirred at 25 °C for 12 h. After post-treatment, 104.1 mg of primary amine salt was obtained. Property: white solid, isolation yield: 63%; melting point: 222 - 224 °C; 1 H NMR(400 MHz, CD3OD): δ(ppm) δ 4.87(s, 3H, NH3), 2.30 - 2.19(m, 1H), 1.78 - 1.63(m, 2H), 1.59 - 1.37(m, 8H), 1.28 - 1.14(m, 2H), 0.92(s, 6H); 13 C NMR(100 MHz, CD3OD): δ(ppm) 120.4(q, J = 318.3 Hz), 53.0, 49.4, 46.0, 41.4, 38.6, 32.1, 29.8, 28.7; 19 F NMR(376 MHz, CD3OD): δ(ppm) -80.04; HRMS(ESI-TOF) m / z: [M-TfO] + Calcd for C 12 H22N + 180.1747; Found 180.1753.

[0272] Gram-scale preparation of Example 72: In a dry round-bottom flask, supported catalyst iron octachlorophthalocyanine (5 mol%, supported on 32 g of silica), compound 1 (8.0 mmol), dioxane solvent (32.0 mL), and an aqueous solution (608.0 mL) of nitrogen source 2 (24.0 mmol) were added in sequence. The reaction solution was stirred at 25 °C for 24 h and monitored by GC-MS until compound 1 was completely consumed to form the primary amine product. After the reaction was completed, the reaction solution was filtered, and the catalyst in the filter cake was washed with water. The filtrates were combined and extracted with ethyl acetate (100 mL) to remove organic impurities. The aqueous layer was concentrated by rotary evaporation under reduced pressure and purified by column chromatography to obtain 1.54 g of the primary amine salt product. Property: white solid, isolation yield: 58%.

[0273] General synthetic process IV:

[0274]

[0275] In a dry round-bottom flask, supported catalyst iron octachlorophthalocyanine (5 mol%, supported on 2 g of silica), compound 1 (0.5 mmol), dioxane solvent (2 mL), and an aqueous solution (38 mL) of nitrogen source 2 (1.5 mmol) were successively added. The reaction mixture was stirred at 25 °C for 12 h and monitored by TLC until compound 1 was completely consumed, yielding primary amine product 3. After the reaction, 5 mL of sodium hydroxide aqueous solution (2.5 mol / L) was added to promote the cyclization reaction, and the reaction was monitored by TLC until the primary amine product was completely converted to the cyclization product. Under ice bath conditions, trifluoromethanesulfonic acid (2.4 mL) was added until pH = 1.5, and after stirring at 25 °C for 1 h, the solvent was removed by rotary evaporation under reduced pressure, and the cyclization product 4 was obtained by column chromatography purification.

[0276] Example 73, Synthesis of

[0277] Using general synthetic process IV. The reaction mixture was stirred at 25 °C for 12 h, and after work-up, 96.6 mg of the cyclization product was obtained. Appearance: brown liquid, isolated yield: 65%; 1 1H NMR (400 MHz, CD3OD): δ (ppm) 7.63 - 7.29 (m, 5H), 4.89 (s, 2H, NH2), 4.75 - 4.53 (m, 1H), 3.56 - 3.37 (m, 2H), 2.56 - 2.40 (m, 1H), 2.40 - 2.07 (m, 3H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 134.5, 129.2, 129.0, 127.2, 120.4 (q, J = 318.5 Hz), 63.3, 45.1, 30.3, 23.4; 19 19F NMR (376 MHz, CD3OD): δ (ppm) -80.08; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 10 H 14 N + 148.1121; Found 148.1129.

[0278] Example 74, Synthesis of

[0279] Using general synthetic process IV. The reaction mixture was stirred at 25 °C for 12 h, and after work-up, 116.7 mg of the cyclization product was obtained. Appearance: colorless liquid, isolated yield: 75%; 11H NMR (400 MHz, CD3OD): δ (ppm) 7.58 - 7.30 (m, 5H), 4.98 (brs, 2H, NH2), 4.24 (dd, J = 11.6 Hz, 3.2 Hz, 1H), 3.52 - 3.42 (m, 1H), 3.27 - 3.04 (m, 1H), 2.16 - 1.89 (m, 4H), 1.89 - 1.64 (m, 2H); 13 13C NMR (100 MHz, CD3OD): δ (ppm) 136.9, 129.1, 128.9, 126.8, 60.7, 45.4, 29.9, 22.4, 21.7; 19 19F NMR (376 MHz, CD3OD) δ (ppm) -80.01; HRMS (ESI-TOF) m / z: [M-TfO] + Calcd for C 11 H 16 N + 162.1277; Found 162.1286.

[0280] General synthetic process five:

[0281]

[0282] In a dry round-bottom flask, successively add iron octachlorophthalocyanine (5 mol%) as the catalyst, compound 1 (0.5 mmol), dioxane solvent (2 mL), and an aqueous solution (38 mL) of nitrogen source 2 (1.5 mmol). The reaction solution is stirred and reacted at 20 - 100 °C for 12 - 36 h, monitored by TLC until compound 1 is completely consumed to form the primary amine product 3. After the reaction is completed, 5 mL of an aqueous solution of NaOH (2.5 mol / L) is added to promote the cyclization reaction, and monitored by TLC until the primary amine product is completely converted to form the cyclized product. Then, the aqueous phase is extracted with ethyl acetate, the organic phase is washed with saturated brine, the solvent is rotary evaporated under reduced pressure, and column chromatography purification is carried out to obtain the cyclized product 4.

[0283] Example 75, Synthesis of

[0284] The general synthetic process five is adopted. The reaction solution is stirred and reacted at 60 °C for 36 h. After post-treatment, 55.2 mg of the cyclized product is obtained. Appearance: yellow solid, isolation yield: 75%; melting point: 152 - 154 °C; 11H NMR (400 MHz, CDCl3): δ (ppm) 8.02 (brs, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.61 - 7.50 (m, 1H), 7.50 - 7.36 (m, 2H), 4.70 (q, J = 6.7 Hz, 1H), 1.50 (d, J = 6.7 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 171.2, 149.0, 131.9, 131.7, 128.0, 123.7, 122.2, 52.7, 20.3; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C9H9NNaO + 170.0576; Found 170.0583.

[0285] Example 76, Synthesis

[0286] Using general synthetic process five. The reaction solution was stirred at 50 °C for 16 h, and after work-up, 49.1 mg of the cyclized product was obtained. Appearance: white solid, isolation yield: 61%; melting point: 68 - 70 °C; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.50 - 7.15 (m, 5H), 6.11 (brs, 1H), 4.78 (t, J = 7.2 Hz, 1H), 2.73 - 2.31 (m, 3H), 2.10 - 1.91 (m, 1H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 179.0, 142.5, 129.0, 128.0, 125.7, 58.1, 31.5, 30.4; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 10 H 11 NNaO + 184.0733; Found 184.0732.

[0287] Example 77, Synthesis

[0288] Using general synthetic process five. The reaction solution was stirred at 60 °C for 36 h, and after work-up, 53.5 mg of the cyclized product was obtained. Appearance: white solid, isolation yield: 56%; melting point: 123 - 125 °C; 11H NMR (400 MHz, CDCl3): δ (ppm) 7.19 - 7.08 (m, 2H), 6.88 - 6.73 (m, 2H), 6.70 (brs, 1H), 4.62 (t, J = 7.1 Hz, 1H), 3.71 (s, 3H), 2.49 - 2.23 (m, 3H), 1.92 - 1.76 (m, 1H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 178.7, 159.2, 134.6, 126.9, 114.2, 57.7, 55.3, 31.5, 30.5; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 11 H 13 NNaO2 + 214.0838; Found 214.0844。

[0289] Example 78, Synthesis of

[0290] Using the general synthetic procedure V. The reaction mixture was stirred at 60 °C for 36 h. After workup, 46.0 mg of the cyclized product was obtained. Appearance: white solid, isolation yield: 38%; melting point: 138 - 140 °C; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.56 - 7.42 (m, 2H), 7.23 - 7.09 (m, 2H), 6.97 (brs, 1H), 4.73 (t, J = 7.1 Hz, 1H), 2.64 - 2.48 (m, 1H), 2.48 - 2.27 (m, 2H), 2.01 - 1.75 (m, 1H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 178.9, 141.6, 132.0, 127.4, 121.7, 57.6, 31.2, 30.4; HRMS (ESI-TOF) m / z: [M+Na] + Calcd forC 10 H 10 79 BrNNaO + 261.9838; Found 261.9829; Calcd for C 10 H 10 81 BrNNaO + 263.9818; Found263.9810。

[0291] Example 79, Synthesis of

[0292] Using general synthetic process V. The reaction solution was stirred at 50 °C for 16 h. After post-treatment, 38.5 mg of the cyclized product was obtained. Appearance: white solid. Isolated yield: 44%; Melting point: 131 - 135 °C; 1 1H NMR (400 MHz, CDCl3): δ (ppm) 7.48 - 7.20 (m, 5H), 6.08 (brs, 1H), 4.57 (dd, J = 9.1 Hz, 4.6 Hz, 1H), 2.58 - 2.36 (m, 2H), 2.22 - 2.01 (m, 1H), 1.98 - 1.86 (m, 1H), 1.86 - 1.74 (m, 1H), 1.74 - 1.61 (m, 1H); 13 13C NMR (100 MHz, CDCl3): δ (ppm) 172.4, 142.6, 128.8, 127.9, 126.1, 57.7, 32.2, 31.3, 19.7; HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 11 H 13 NNaO + 198.0889; Found 198.0899.

[0293] The beneficial effects of the present invention are demonstrated by the following experimental examples.

[0294] Experimental Example 1. Screening of the types of reaction catalysts and catalytic reaction conditions of the present invention

[0295] 1. Screening of catalyst types

[0296] The product was prepared according to the following reaction formula:

[0297] In a dry round-bottom flask, different catalysts C1 - C22 (10 mol%) as shown, compound 1a (0.1 mmol) and an aqueous solution (2 mL) of nitrogen source 2 (0.2 mmol) were successively added. The reaction solution was stirred at room temperature for 12 h and monitored by TLC or GC-MS until compound 1a was completely consumed to form the primary amine product. Then, the solvent was removed by rotary evaporation under reduced pressure and the primary amine product 3a was obtained by column chromatography purification. Figure 1 An ultraviolet (UV) quantitative analysis method was established by HPLC and a standard curve for calculating the analytical yield of the product was plotted (as

[0298]

[0299] Figure 2 ​As shown; after the reaction is completed, the reaction solution is analyzed by HPLC, and the ultraviolet absorption ratio of the primary amine product to the internal standard (1,3,5-trimethoxybenzene) at 260 nm is calculated. According to the standard curve, the analytical yield of the primary amine product after the reaction catalyzed by different catalysts is calculated.

[0300] Table 1. Analytical Yields of Primary Amine Products after the Reaction Catalyzed by Different Catalysts

[0301]

[0302] The results are shown in Table 1. It can be seen that catalysts C5 - C9 all have good catalytic effects, and catalyst C5 (iron octachlorophthalocyanine) is the most preferred.

[0303] 2. Screening of Reaction Solvent Types

[0304] On the basis of the above catalytic reaction conditions, using C5 (iron octachlorophthalocyanine) as the catalyst, the screening of reaction solvent types shown in Table 2 is continued.

[0305]

[0306] Table 2. Analytical Yields of Primary Amine Products Obtained under Different Reaction Solvents

[0307]

[0308] The results are shown in Table 2. It can be seen that when using water, a mixed solution of N,N-dimethylformamide (DMF) and water, a mixed solution of acetonitrile (MeCN) and water, and a mixed solution of 1,4-dioxane (1,4-Dioxane) and water as reaction solvents, all have good catalytic effects, and the solution obtained by mixing 1,4-dioxane and water in a ratio of 1:19 is the most preferred.

[0309] 3. Screening of the Dosage of Catalyst C5 and the Reaction Concentration of the Substrate

[0310] On the basis of the above catalytic reaction conditions, using the solution obtained by mixing 1,4-dioxane and water in a ratio of 1:19 as the reaction solvent, the screening of the molar percentage of catalyst C5 in compound 1a and the concentration of compound 1a shown in Table 3 is continued.

[0311]

[0312] Table 3. Analytical Yields of Primary Amine Products Obtained under Different Molar Percentages of Catalyst C5 and Concentrations of Compound 1a

[0313]

[0314] The results are shown in Table 3. It can be seen that under the conditions where the molar percentage of catalyst C5 is 2 mol% - 10 mol% and the concentration of compound 1a is 0.00625 M - 0.05 M, good catalytic effects are achieved. The most preferred conditions are that the molar percentage of catalyst C5 is 5 mol% and the concentration of compound 1a is 0.0125 M.

[0315] 4. Screening of the types and equivalents of nitrogen source 2

[0316] On the basis of the above catalytic reaction conditions, while controlling the molar percentage of catalyst C5 to be 5 mol% and the concentration of compound 1a to be 0.0125 M, the screening of the types and equivalents of nitrogen source 2 (taking the amount of compound 1a as 1 equivalent) shown in Table 4 was continued.

[0317]

[0318] Table 4. Analytical yields of primary amine products obtained under different types and equivalents of nitrogen source 2

[0319]

[0320]

[0321] (Note: Supported catalyst C5 was used)

[0322] The results are shown in Table 4. It can be seen that when using PivONH2·TfOH, AcONH2·TfOH, and PivONH2·HCl as nitrogen sources and controlling the nitrogen source equivalent to be 1 - 3, good catalytic effects are achieved. When using PivONH2·TfOH as the nitrogen source and controlling the nitrogen source equivalent to be 3, it is the most preferred.

[0323] In summary, the present invention provides a catalyst suitable for the primary amination reaction of sp 3 -C-H bonds, and a method for preparing a primary amine compound by using this catalyst to catalyze the primary amination reaction of sp 3 -C-H bonds. The method of the present invention has high generality, broad substrate applicability, is environmentally friendly, has mild reaction conditions, is not harsh, the reaction operation is simple, and has potential industrial application prospects.

Claims

1. Use of the compound of formula I as a catalyst for the sp 3 -carbon-hydrogen bond primary amination reaction: Among them, The compound shown in Formula I is C5, C6, C7, C8 or C9; In C5, R a = R d = H, R b = R c = Cl, M = Fe(II); In C6, R a = R d = H, R b = R c = Cl, M = Fe(III)Cl; In C7, R a = R b = R c = R d = Cl, M = Fe(II); In C8, R a = R d = H; R b = R c = F; M = Fe(II); In C9, R a = R b = R c = R d = F; M = Fe(II).

2. The use according to claim 1, wherein The compound shown in Formula I is iron octachlorophthalocyanine.

3. The use according to any one of claims 1 to 2, characterized in that, The said sp 3 - The primary amination reaction of C-H bond uses Compound 1 and Compound 2 as reactants, and Compound 3 is generated under the action of a catalyst. The reaction formula is as follows: Among them, R, R 1 , R 2 are each independently any group, or any two or three of R, R 1 , R 2 are connected to form a substituted or unsubstituted ring; R 3 is pivaloyl or acetyl, and A is sulfonic acid, hydrochloric acid, sulfuric acid, acetic acid or none.

4. The use according to claim 3, wherein, R 3 is pivaloyl, and A is sulfonic acid.

5. The use according to claim 4, wherein A is trifluoromethanesulfonic acid.

6. The use according to claim 3, characterized in that, The conditions of the reaction are: in a solvent, reacting at 20 - 100 °C for 12 - 120 h; and / or, the molar ratio of Compound 1 to Compound 2 is 1:(1 - 3), the molar ratio of Compound 1 to the catalyst is 100:(2 - 10), and the concentration of Compound 1 is 0.00625 M - 0.05 M.

7. The use according to claim 6, characterized in that The temperature of the reaction is 25 °C and the reaction time is 12 h; and / or, the molar ratio of Compound 1 to Compound 2 is 1:3, the molar ratio of Compound 1 to the catalyst is 100:5, and the concentration of Compound 1 is 0.0125 M.

8. The use according to claim 6, characterized in that, The solvent is water, a mixed solvent of acetonitrile and water, a mixed solvent of dioxane and water, or a mixed solvent of N,N - dimethylformamide and water.

9. The use according to claim 8, wherein The solvent is a mixed solvent of dioxane and water.

10. A method for preparing a primary amine compound, characterized in that, It includes the step of reacting Compound 1 and Compound 2 as reactants under the action of a catalyst to prepare a primary amine compound 3; the reaction formula is as follows: Among them, R, R 1 , R 2 are each independently any group, or any two or three of R, R 1 , R 2 are connected to form a substituted or unsubstituted ring; R 3 is pivaloyl or acetyl, A is sulfonic acid, hydrochloric acid, sulfuric acid, acetic acid or none; The catalyst is the compound shown in Formula I: wherein, the compound shown in Formula I is C5, C6, C7, C8 or C9; In C5, R a = R d = H, R b = R c = Cl, M = Fe(II); In C6, R a = R d = H, R b = R c = Cl, M = Fe(III)Cl; In C7, R a = R b = R c = R d = Cl, M = Fe(II); In C8, R a = R d = H; R b = R c = F; M = Fe(II); In C9, R a = R b = R c = R d = F; M = Fe(II).

11. The method according to claim 10, wherein R 3 is pivaloyl group, and A is sulfonic acid.

12. The method according to claim 11, wherein A is trifluoromethanesulfonic acid.

13. The method according to claim 10, wherein The conditions of the reaction are: in a solvent, reacting at 20 - 100 °C for 12 - 120 h; and / or, the molar ratio of Compound 1 to Compound 2 is 1:(1 - 3), the molar ratio of Compound 1 to the catalyst is 100:(2 - 10), and the concentration of Compound 1 is 0.00625 M - 0.05 M.

14. The method according to claim 13, wherein The temperature of the reaction is 25 °C and the reaction time is 12 h; and / or, the molar ratio of Compound 1 to Compound 2 is 1:3, the molar ratio of Compound 1 to the catalyst is 100:5, and the concentration of Compound 1 is 0.0125 M.

15. The method according to claim 13, wherein The solvent is water, a mixed solvent of acetonitrile and water, a mixed solvent of dioxane and water, or a mixed solvent of N,N - dimethylformamide and water.

16. The method according to claim 15, wherein The solvent is a mixed solvent of dioxane and water.

17. The method according to any one of claims 10 to 16, characterized in that The R is a substituted or unsubstituted 5 - 6 - membered aromatic ring, 5 - 6 - membered heteroaromatic ring, 5 - 6 - membered fused 5 - 6 - membered aromatic ring or 5 - 6 - membered fused 5 - 6 - membered heteroaromatic ring.

18. The method according to claim 17, wherein R 1 、R 2 are each independently any group, and the reaction formula is as follows: Among them, R a , R b , R c , R d , R e are each independently selected from hydrogen or any group other than hydrogen; Ring A is selected from:

19. The method according to claim 18, characterized in that, The R a , R b , R c , R d , R e are each independently selected from hydrogen, halogen, phenyl substituted with a linear or branched alkyl group having C 1～10 , phenyl, linear or branched alkyl group having C 1～10 , linear or branched alkoxy group having C 1～10 ; and / or, said R 1 , R 2 are each independently selected from hydrogen, a 3- to 6-membered saturated cycloalkyl group, a straight-chain or branched-chain alkyl group having C 1～10 , a phenyl group, a phenyl-substituted straight-chain or branched-chain alkyl group having C 1～10 , or R 1 , R 2 are connected to form a ring.

20. The method according to claim 18, wherein The reaction conditions are: in a mixed solvent of dioxane and water, reacting at 20 - 80 °C for 12 - 120 h.

21. The method according to claim 20, wherein The reaction conditions are: in a mixed solvent of dioxane and water, reacting at 25 - 70 °C for 12 - 120 h.

22. The method according to claim 21, wherein The reaction conditions are: in a mixed solvent of dioxane and water, reacting at 25 - 60 °C for 12 - 120 h.

23. The method according to claim 17, wherein R 1 is hydrogen, and R 2 is connected to R to form a ring, and the reaction formula is as follows: Among them, R f , R g , R h , R i are each independently selected from hydrogen or any group other than hydrogen, X is CH2, O or NR', n is any integer from 0 to 6; R' is hydrogen, C 1～18 alkyl, benzyl or an amino protecting group.

24. The method according to claim 23, wherein R' is hydrogen, methyl, ethyl, benzyl, benzoyl or Boc.

25. The method according to claim 23, wherein Said R f , R g , R h , R i are each independently selected from hydrogen, halogen, phenyl substituted with a linear or branched alkyl group of C 1～10 , phenyl, linear or branched alkyl group of C 1～10 , linear or branched alkoxy group of C 1～10 , or two adjacent groups among R f , R g , R h , R i are linked to form a ring.

26. The method according to claim 23, wherein The reaction conditions are: in a mixed solvent of dioxane and water, reacting at 25 - 60 °C for 12 - 120 h.

27. The method according to any one of claims 10 to 16, characterized in that The R is a substituted or unsubstituted alkenyl group.

28. The method according to claim 27, wherein wherein R is wherein R j , R k , R m is any group.

29. The method according to claim 28, wherein R 1 and R 2 are each independently any group, and the reaction formula is as follows:

30. The method according to claim 29, characterized in that, The said R 1 , R 2 are each independently selected from hydrogen, a straight-chain or branched-chain alkyl group of C 1～10 ; R j , R k , R m are each independently selected from hydrogen, a straight-chain or branched-chain alkyl group of C 1～10 .

31. The method according to claim 29, wherein The reaction conditions are: in dioxane and water, reacting at 20 - 60 °C for 12 - 48 h.

32. The method according to claim 31, characterized in that, The reaction conditions are: in dioxane and water, reacting at 25 - 40 °C for 12 - 24 h.

33. The method according to claim 27, wherein Said R is Wherein R n , R p is an arbitrary group.

34. The method according to claim 33, wherein R 1 and R 2 are each independently any group, and the reaction formula is as follows:

35. The method according to claim 34, wherein The reaction conditions are: in a mixed solvent of dioxane and water, reacting at 20 - 60 °C for 12 - 48 h.

36. The method according to any one of claims 10 to 16, characterized in that wherein R is a substituted or unsubstituted linear or branched alkyl group, R 1 , R 2 are each independently any group; The substituent is any one or more of halogen, ester group, alkoxy group, phenyl group, and benzyl group.

37. The method according to claim 36, wherein R is C 1～18 a straight-chain or branched-chain alkyl group, R 1 , R 2 and R 1～18 are each independently selected from hydrogen or a straight-chain or branched-chain alkyl group of C 38. The method according to claim 37, wherein R is a straight-chain or branched-chain alkyl group of C 1～10 , and R 1 , R 2 are each independently selected from hydrogen or a straight-chain alkyl group of C 1～10 .

39. The method according to any one of claims 10 to 16, characterized in that The R and R 1 are connected to form a ring, and R 2 is hydrogen.

40. The method according to claim 39, characterized in that, The R and R 1 are connected to form a saturated ring, and the reaction formula is as follows: Among them, Y is CHR'', and r is any integer from 0 to 12; R'' is any group.

41. The method according to claim 40, wherein R'' is hydrogen, methyl, ethyl or benzyl.

42. The method according to claim 40, wherein The reaction conditions are as follows: reacting in a mixed solvent of dioxane and water at 25 - 80 °C for 12 - 48 h.

43. The method according to any one of claims 10 to 16, characterized in that, Compound 1 is any of the following structures:

44. The method according to any one of claims 10 to 16, characterized in that R, R 1 , R 2 are connected to form a bridged ring.

45. The method according to claim 44, wherein Compound 1 is or The reaction formula is as follows: or 46. The method according to claim 45, wherein The reaction conditions are as follows: reacting in a mixed solvent of dioxane and water at 20 - 80 °C for 12 - 72 h.

47. The method according to claim 46, wherein The reaction conditions are as follows: reacting in a mixed solvent of dioxane and water at 25 °C for 12 h.

48. The method according to any one of claims 10 to 16, characterized in that The R is a substituted or unsubstituted alkynyl group.

49. The method according to claim 48, wherein R is wherein R q is any group.

50. The method according to claim 49, characterized in that, R 1 and R 2 are each independently any group, and the reaction formula is as follows:

51. The method according to claim 50, wherein, R 1 and R 2 are each independently selected from hydrogen, phenyl, a straight-chain or branched-chain alkyl group of C 1～10 , R q is selected from hydrogen, phenyl, a straight-chain or branched-chain alkyl group of C 1～10 .

52. The method according to claim 51, characterized in that, The reaction conditions are as follows: reacting in a mixed solvent of dioxane and water at 20 - 60 °C for 12 - 48 h.

53. The method according to any one of claims 10 to 16, characterized in that, The structure of Compound 1 is selected from:

54. A method for synthesizing cyclic secondary amine or lactam compounds, characterized in that, It includes the following steps: preparing a primary amine compound according to the method described in claim 36; cyclizing the primary amine compound under the action of a base to generate a cyclic secondary amine or an inner amide compound.

55. The method according to claim 54, wherein R is a substituted C 1～5 linear alkyl group, R 1 , R 2 and R are each independently any group; the substituent is a halogen or an ester group; The reaction formula is as follows: Among them, X is halogen or alkoxy group, and n is an integer from 1 to 3.

56. The method according to claim 55, wherein The R 1 is a substituted or unsubstituted phenyl group, R 2 is hydrogen, n is 1 or 2; the substituent of the substitution is a halogen or a methyl ester group.

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