Fluorine sulfonyl-containing guanidine compound as well as preparation method and application thereof

Abstract

The invention discloses a guanidine compound containing fluorine sulfonyl as well as a preparation method and application of the guanidine compound. The invention provides fluorine-containing sulfonyl guanidine as shown in a formula 1. The fluorosulfonyl guanidine disclosed by the invention can react with phenol or amine molecules, and sulfamide guanidyl is introduced into the molecules. According to the compound, amine and phenolic compounds can be converted into aminosulfonyl guanidine and N-amidino sulfamate compounds by a process which is mild in condition, simple to operate and easy to amplify, and the substrate universality is good. # imgabs0 #

Description

Technical Field

[0001] The invention relates to a fluorine-sulfonyl-containing guanidine compound and a preparation method and application thereof. Background Art

[0002] Guanidine compounds have the general structural formula of R1-N=C(NR2R3)(NR4R5), where R1, R2, R3, R4 and R5=H, aryl or alkyl. Due to their strong alkalinity, this class of compounds is widely used in many base-catalyzed organic reactions, for example, BTMG is a powerful SuFEx catalyst. Guanidine has very important functions in life chemistry. It is the basic side chain in arginine and plays an important role in a variety of arginine-containing proteins and peptides. In addition, a series of natural products containing single or multiple guanidine groups isolated from microorganisms, terrestrial organisms, marine organisms and plants have outstanding pharmacological and biological activities, such as antiviral and antitumor. Guanidine compounds are also hot research objects in medicinal chemistry. Rosuvastatin is one of the best-selling drugs for the treatment of high cholesterol and prevention of cardiovascular disease. Zanamivir is the first commercialized neuraminidase inhibitor, which inhibits the aggregation and release of influenza viruses in infected cells by inhibiting the neuraminidase of influenza viruses. Guanidine compounds are also used in other fields, such as crystal engineering, supramolecular chemistry, sweetener research and development, etc. Therefore, the efficient preparation of guanidine compounds under mild conditions has important scientific research and application value.

[0003] At present, the most commonly used method for synthesizing guanidine compounds is to use various amine compounds and guanidation reagents for reaction. The addition reaction of cyanamide and amine compounds is an earlier method for preparing guanidine compounds. Widely used guanidation reagents include thioureas, isothioureas, guanylsulfonic acids, cyanamides, carbodiimides, trifluoromethanesulfonylguanidines, guanylpyrazoles, guanylbenzotriazoles, etc.

[0004] N,N'-di-tert-butyloxycarbonyl-N"-(trifluoromethylsulfonyl)guanidine is a guanidation reagent first reported by the Goodman group in 1998. Due to its excellent reactivity, this compound can efficiently convert various primary and secondary amines into corresponding Boc-protected guanidine compounds at room temperature and can be used in solid phase synthesis. However, the synthesis cost of this type of compound is relatively high, which limits its large-scale application.

[0005]

[0006] N-Benzyltrifluoromethanesulfonamide can be prepared by reacting benzylamine and trifluoromethanesulfonic anhydride in the presence of triethylamine in a dichloromethane solvent (J.Am.Chem.Soc.2018,140,3202–3205), while the reaction of benzylamine and sulfuryl fluoride gas under the same conditions (triethylamine as a base and dichloromethane as a solvent) fails to give the corresponding product N-benzylfluorosulfonamide (Angew.Chem.Int.Ed.2014,53,2-21).

[0007] This is because the properties of the -SO2F group and the -SO2CF3 group are very different. The SF bond in the -SO2F group can be activated under specific conditions and react with oxygen-containing or nitrogen-containing nucleophiles to generate -SO2-OR or -SO2-NRR' (R and R' are independently aromatic or alkyl) (Angew.Chem.Int.Ed.2014,53,2-21); while the SC bond in the -SO2CF3 group is much more stable and will not react with nucleophiles (Journal of Fluorine Chemistry.1998,91,9-12).

[0008] N,N'-di-tert-butyloxycarbonyl-N"-(fluorosulfonyl)guanidine is a guanidation reagent first reported by Dong Jiajia's research group in 2022. This compound can efficiently convert various aliphatic amines and aromatic amines into corresponding Boc-protected guanidine compounds at room temperature. The synthesis cost of this compound is low and it is easy to scale up industrially. The reactivity of this compound with amine compounds is better than almost all reported guanidation reagents. This guanidation reagent has extremely high selectivity and reactivity for amine compounds, and its electrophilic site is based on the electrophilic guanidine central carbon atom.

[0009]

[0010] N,N'-di-tert-butyloxycarbonyl-N"-(fluorosulfonyl)guanidine was easily synthesized using the SuFEx reaction and exhibited superior performance compared to other commercial guanidation reagents. More interestingly, N,N'-di-tert-butyloxycarbonyl-N"-(fluorosulfonyl)guanidine reacted faster with amines in a two-phase system. Once N,N'-di-tert-butyloxycarbonyl-N"-(fluorosulfonyl)guanidine and amines were mixed in MeCN / H2O, the reaction mixture spontaneously generated an oil / water interface by forming oil droplets and accelerated the reaction rate under such conditions. This unique "on-water" reactivity adds a new model of water interface catalysis.

[0011] Sulfonamides and sulfamates are valuable drug groups that have been found in a variety of biologically active compounds. Meanwhile, sulfonylguanidines exhibit a wide range of biological activities, such as the anti-ulcer agent osutidine and the cannabinoid CB1 inhibitor ibipinabant. However, analogs of sulfonylguanidines, sulfamylguanidines, and N-amidinosulfamates have been rarely explored, mainly due to the lack of reliable synthetic methods. Summary of the invention

[0012] The technical problem to be solved by the present invention is that the existing guanidation reagents are mainly used for the synthesis and promotion of guanidine compounds, however, there is a lack of reliable synthesis methods for the analogs of sulfonylguanidine, aminosulfonylguanidine and N-amidinosulfamate. To this end, a fluorinated sulfonyl guanidine compound and a preparation method and application thereof are provided. The fluorinated sulfonylguanidine can efficiently convert amines and phenols into aminosulfonylguanidine and N-amidinosulfamate compounds, has good substrate universality, and the preparation method of the fluorinated sulfonylguanidine is simple, easy to scale up production, simple to operate, and has good academic and application value.

[0013] The present invention solves the above technical problems through the following technical solutions.

[0014] The present invention provides a fluorosulfonylguanidine as shown in Formula 1,

[0015]

[0016] The present invention provides a method for preparing a fluorosulfonylguanidine as shown in Formula 1, which comprises the following steps: in the presence of a base, compound 2 and sulfuryl fluoride (SO2F2) react in a solvent to obtain a fluorosulfonylguanidine compound as shown in Formula 1;

[0017]

[0018] In the preparation method of the fluorosulfonylguanidine as shown in Formula 1, the solvent may be one or more of a hydrocarbon solvent, a halogenated hydrocarbon solvent, a nitrogen-containing compound solvent, an ether solvent, an ester solvent, a ketone solvent and a sulfur-containing compound solvent, for example, a nitrogen-containing compound solvent; wherein the hydrocarbon solvent may be benzene and / or toluene; the halogenated hydrocarbon solvent may be one or more of dichloromethane, 1,2-dichloroethane and chloroform; the nitrogen-containing compound solvent may be one or more of acetonitrile, N,N-dimethylformamide (DMF) and N-methylpyrrolidone, for example, N,N-dimethylformamide (DMF); the ether solvent may be one or more of 1,4-dioxane, diethyl ether, methyl tert-butyl ether (MTBE) and tetrahydrofuran; the ester solvent may be ethyl acetate; the ketone solvent may be acetone; the sulfur-containing compound solvent may be dimethyl sulfoxide (DMSO).

[0019] In the preparation method of the fluorosulfonyl group as shown in Formula 1, the base may be one or more of an alkali metal carbonate, an alkali metal phosphate, an alkali metal hydroxide, an alkali metal bicarbonate and an organic base, for example, an organic base; wherein the alkali metal carbonate may be one or more of potassium carbonate, cesium carbonate and sodium carbonate, preferably cesium carbonate and / or potassium carbonate, more preferably potassium carbonate; the alkali metal phosphate may be tripotassium phosphate; the alkali metal hydroxide may be sodium hydroxide and / or potassium hydroxide; the alkali metal bicarbonate may be sodium bicarbonate and / or potassium bicarbonate; the organic base may be triethylamine and / or N,N-diisopropylethylamine.

[0020] In the preparation method of fluorosulfonylguanidine as shown in Formula 1, the introduction method of sulfuryl fluoride can be conventional in the art and is not particularly limited here. For example, the reaction system can be evacuated to negative pressure and then sulfuryl fluoride gas can be introduced at once.

[0021] In the preparation method of the fluorosulfonylguanidine as shown in Formula 1, the molar ratio of the compound 2 to the sulfuryl fluoride can be conventional in the art, such as (1.2-2):1, such as 1.5:1.

[0022] In the method for preparing the fluorosulfonylguanidine as shown in Formula 1, the molar volume ratio of the compound 2 and the solvent can be conventional in the art, such as 0.5 mol / L to 3 mol / L, and for example 2.26 mol / L.

[0023] In the method for preparing the fluorosulfonyl group as shown in Formula 1, the molar ratio of the compound 2 to the base can be conventional in the art, such as 1:(2-7), and another example is 1:3.

[0024] In the method for preparing the fluorosulfonyl group as shown in Formula 1, the reaction temperature can be conventional in the art, such as -20°C to 60°C, such as 50°C.

[0025] In the preparation method of fluorosulfonylguanidine as shown in Formula 1, the progress of the reaction can be 19 F is monitored, and the reaction end point is generally taken as the time when the sulfuryl fluoride gas is completely consumed. The reaction time can be conventional in the art, such as 0.5-48 hours, and for example 5 hours.

[0026] In the preparation method of the fluorosulfonylguanidine as shown in Formula 1, the preparation method may further include post-treatment, and the post-treatment includes the following steps: quenching and extraction.

[0027] In the preparation method of the fluorosulfonyl group as shown in Formula 1, the quenching is quenching by adding water.

[0028] In the preparation method of fluorosulfonylguanidine as shown in Formula 1, in the post-treatment step, the extraction solvent is water and an organic solvent, and the type of the organic solvent can be conventional in the art, preferably methyl tert-butyl ether and / or ethyl acetate. Wherein, the compound 2 is preferably in the form of a guanidine salt; the guanidine salt is, for example, one or more of guanidine hydrochloride, guanidine sulfate, guanidine nitrate and guanidine carbonate, and for example, guanidine hydrochloride.

[0029] The compound 2 is directly subjected to the preparation reaction of the fluorosulfonylguanidine shown in Formula 1 as described above without being isolated.

[0030] The present invention provides an application of the fluorosulfonylguanidine as shown in Formula 1 described above in the preparation of a guanidine compound.

[0031] In one embodiment, the application comprises the following steps:

[0032] In a solvent, the fluorosulfonylguanidine as shown in Formula 1 and the The amine compound containing the structural fragment shown in formula A is reacted to obtain a compound containing the structural fragment shown in formula A;

[0033]

[0034] In a solvent, the fluorosulfonylguanidine as shown in Formula 1 and the The alcohol-phenol compound containing the structural fragment shown in formula A is reacted to obtain a compound containing the structural fragment shown in formula B;

[0035]

[0036] In the application, the solvent may be an organic solvent, water, or a mixed solvent of an organic solvent and water.

[0037] In the application, when the solvent is a mixed solvent of an organic solvent and water, the volume ratio of the organic solvent to water may be 1:1.

[0038] In the application, when the solvent comprises an organic solvent, the organic solvent is preferably one or more of acetonitrile, methanol, DMF, dimethyl sulfoxide, sulfolane, dichloromethane and ethyl acetate, such as one or more of acetonitrile, methanol and DMF.

[0039] In the application, preferably, the solvent is an acetonitrile / water solvent system, methanol or DMF.

[0040] In the application, the molar ratio of the amine compound or alcohol-phenol compound to the fluorosulfonylguanidine compound as described in Formula 1 can be conventional in the art, preferably 1:(0.3-2), for example 1:0.33, 1:0.5, 1:0.6, 1:0.83, 1:1 or 1:2.

[0041] In the application, the molar volume ratio of the amine compound or alcohol-phenol compound to the solvent can be conventional in the art, preferably 0.13 mol / L to 1.5 mol / L, for example: 0.13 mol / L, 0.2 mol / L, 0.25 mol / L, 0.33 mol / L, 0.4 mol / L, 0.5 mol / L, 0.6 mol / L, 0.63 mol / L, 1.0 mol / L or 1.5 mol / L.

[0042] In a certain embodiment of the application, the reaction may further comprise a base, which is one or more of an alkali metal carbonate, an alkali metal phosphate, an alkali metal hydroxide, an alkali metal bicarbonate and an organic base, such as N,N-diisopropylethylamine and / or triethylenediamine.

[0043] In one embodiment of the application, when the reaction further comprises a base, the molar ratio of the amine compound to the base may be 1:(2-3), for example, 1:2, 1:2.2 or 1:3;

[0044] In one embodiment of the application, the reaction only includes the amine compound and / or the phenolic alcohol compound, the fluorosulfonylguanidine compound as described in Formula 1, and the solvent; or, the reaction only includes the amine compound and / or the phenolic alcohol compound, the fluorosulfonylguanidine compound as described in Formula 1, the solvent, and a base.

[0045] In the application, the reaction temperature may be conventional in the art, such as 0-100°C, such as 60-80°C, preferably 70°C.

[0046] In the application, the reaction of the substrate and the fluorosulfonylguanidine compound can be monitored by LC-MS or GC-MS, and the disappearance of the substrate is generally taken as the end point of the reaction. The reaction time can be conventional in the art, such as 5 min-24 h, and 10 min-24 h, and further such as 2 h, 4 h, 16 h, 20 h or 24 h.

[0047] In the application, the post-treatment of the reaction may include the following steps: quenching, washing and solvent removal.

[0048] In the application, in the post-treatment step of the reaction, the quenching process can use water or an aqueous acid solution, preferably water. The acid in the aqueous acid solution can be an organic acid, such as citric acid.

[0049] In the application, in the post-treatment step of the reaction, when an acid aqueous solution is used for quenching, preferably, the acid aqueous solution is added to make the pH value 4.

[0050] In the application, in the post-treatment step of the reaction, the washing process can be performed using water or saturated brine.

[0051] In the application, in the post-treatment step of the reaction, extraction may be further included between the quenching and the washing process, and the type of organic solvent used in the extraction may be conventional in the art, such as ethyl acetate. Preferably, the extraction is performed 3 or 4 times.

[0052] In the application, in the post-treatment step of the reaction, the process of removing the solvent can be carried out by a method of concentration under reduced pressure.

[0053] In the application, the post-treatment step of the reaction may further include purification, and the purification may be column chromatography.

[0054] In a certain embodiment, in the application, the formula The amine compound of the structural fragment shown is Obtain a compound as shown in formula C;

[0055]

[0056] in,

[0057] R 1 and R 2 are independently H, C1-C6 alkyl, C6-C 10 Aryl, benzyl, 4-7 membered heterocyclic and C6-C 10 Aryl, 5-10 membered heteroaryl, or one or more R f substituted 5-10 membered heteroaryl, substituted by one or more R a Substituted C1-C6 alkyl, one or more R b Substituted C6-C 10 Aryl, one or more R c substituted benzyl or one or more R d Substituted 4-7 membered heterocyclic C6-C 10 aryl; and R 1 and R 2 are not H at the same time; when there are multiple substituents, the substituents are the same or different;

[0058] Or, R 1 and R 2 Together with the nitrogen atom therebetween, it forms a 3-7 membered heterocyclic ring or is replaced by one or more R e A substituted 3-7 membered heterocycle; when there are multiple substituents, the substituents are the same or different;

[0059] The 4-7 membered heterocyclic ring is C6-C 10Aryl and one or more R d Substituted 4-7 membered heterocyclic C6-C 10 The heteroatom in the aryl group is selected from one or more of N, O and S, and the number of the heteroatom is 1 to 4;

[0060] The 3-7 membered heterocyclic ring is represented by one or more R e The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of the heteroatom is 1 to 4;

[0061] The 5-10 membered heteroaryl group and one or more R f The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of the heteroatoms is 1 to 4;

[0062] Each R a Independently Carboxyl, benzyl, C2-C6 alkynyl, or hydroxyl; R a-1 is a C1-C6 alkyl group;

[0063] Each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocyclic ring, with one or more R b-5 Substituted 3-7 membered heterocyclic ring, or When there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and the one or more R b-5 The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of the heteroatom is 1 to 4;

[0064] Each R c are independently halogen;

[0065] Each R d Independently 4-7 membered lactam-containing heterocyclic alkyl or Substituted 4-7 membered lactam-containing heterocycloalkyl;

[0066] Each R e Independently C6-C 10 Aryl or one or more R e-1 Substituted C6-C 10 Aryl; when there are multiple substituents, the substituents are the same or different;

[0067] Each R f are independently halogen;

[0068] Each R b-1 are independently C1-C6 alkyl; R b-2 and R b-3 are independently C1-C6 alkyl; or, R b-2 and R b-3 Together with the nitrogen atom therebetween, it forms a 3-7 membered heterocyclic ring or a 3-7 membered heterocyclic ring substituted by one or more C1-C6 alkyl groups; the heteroatoms in the 3-7 membered heterocyclic ring are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; when there are multiple substituents, the substituents are the same or different;

[0069] Each R b-4 is independently a 5-10 membered heteroaryl or is replaced by one or more R b-6 A substituted 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group is a 5-10 membered heteroaryl group having one or more heteroatoms selected from N, O and S, and the number of heteroatoms is 1 to 4; when there are multiple substituents, the substituents are the same or different;

[0070] Each R b-4 Independently or C1-C6 alkyl;

[0071] Each R b-5 are independently hydrogen, or C1-C6 alkyl;

[0072] Each R b-6 are independently C1-C6 alkyl or C1-C6 alkoxy;

[0073] Each R e-1 It is independently a C1-C6 alkyl group substituted by one or more halogens; when there are multiple substituents, the substituents are the same or different.

[0074] In a certain embodiment, in the application, the formula The phenolic alcohol compounds of the structural fragments shown are Obtaining a guanidine sulfonate compound as shown in formula D;

[0075]

[0076] in,

[0077] R 3 C 1-10 Alkyl, with one or more R 1-0 Substituted C 1-10 Alkyl, C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, C(O)R 1-3, 5-12 membered heterocycloalkyl, 1-7 substituted 5-12 membered heterocycloalkyl, 5-10 membered heteroaryl, substituted by one or more R 1-8 Substituted 5-10 membered heteroaryl, C 5-20 Cycloalkyl C 6-14 Aryl, or one or more R 1-9 Substituted C 5-20 Cycloalkyl C 6-14 Aryl; the 5-12 membered heterocycloalkyl and one or more R 1-7 The heteroatoms in the substituted 5-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; the 5-10 membered heteroaryl and the one or more R 1-8 The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4;

[0078] Each R 1-0 are independently halogen, nitro, cyano, oxo, C(O)OR 1-1-1 、C(O)R 1-1-2 NR 1-1-3 R 1-1-4 NR 1-1-3 C(O)R 1-1-4 , OR 1-1-5 , C 6-14 Aryl, one or more R 1-1-7 Substituted C 6-14 Aryl, 5-12 membered heterocycloalkyl, 1-1-8 substituted 5-12 membered heterocycloalkyl, 5-10 membered heteroaryl, substituted by one or more R 1-1-9 Substituted 5-10 membered heteroaryl, C 2-12 Alkynyl, with one or more R 1-1-10 Substituted C 2-12 Alkynyl, vinyl, one or more R 1-1-11 Substituted vinyl, or OS(O)2R 1-1-12 ; Each R 1-1 , R 1-7 , R 1-8 and R 1-9 are independently halogen, nitro, cyano, C2-C6 alkynyl, C(O)OR 1-1-1 、C(O)R 1-1-2 NR 1-1-3 R 1-1-4 NR 1-1-3 C(O)R 1-1-4 , C 1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR1-1-5 ;

[0079] Each R 1-3 are independently hydrogen, NR 1-1-3 R 1-1-4 , C 1-10 Alkyl, with one or more R 1-1-6 Substituted C 1-10 Alkyl, C 6-14 Aryl, one or more R 1-1-7 Substituted C 6-14 Aryl, 5-12 membered heterocycloalkyl, 1-1-8 substituted 5-12 membered heterocycloalkyl, 5-10 membered heteroaryl, or substituted by one or more R 1-1-9 substituted 5-10 membered heteroaryl, vinyl, or one or more R 1-1-11 Replaced vinyl;

[0080] Each R 1-1-1 Independently for C 1-10 Alkyl, with one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl;

[0081] Each R 1-1-2 Independently for C 1-10 Alkyl, with one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl, vinyl, or one or more R 1-1-1-3 Replaced vinyl;

[0082] Each R 1-1-3 and R 1-1-4 are independently hydrogen, C 1-10 Alkyl, with one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl;

[0083] Each R 1-1-5 Independently for C 1-10 Alkyl, or one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C6-14 Aryl;

[0084] Each R 1-1-6 are independently halogen, nitro, cyano, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl;

[0085] Each R 1-1-7 are independently halogen, nitro, cyano, C 1-10 Alkyl, with one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl;

[0086] R 1-1-12 For halogen, C 1-10 Alkyl, or one or more R 1-1-1-1 Substituted C 1-10 alkyl;

[0087] Each R 1-1-13 are independently hydroxyl groups;

[0088] Each R 1-1-8 , R 1-1-9 , R 1-1-10 , R 1-1-11 , R 1-1-1-1 and R 1-1-1-2 are independently halogen, nitro, cyano, C 1-4 Alkyl, halo-C 1-4 Alkyl, -OC 1-4 Alkyl, -NH2, vinyl, ethynyl, C 6-12 Aryl, 5-6 membered heterocycloalkyl, or 5-6 membered heteroaryl;

[0089] The 5-12 membered heterocycloalkyl group and one or more R 1-1-8 The heteroatoms in the substituted 5-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; the 5-10 membered heteroaryl and the one or more R 1-1-9 The heteroatoms in the substituted 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; the heteroatoms in the 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4.

[0090] In one plan,

[0091] R 1 is H;

[0092] R 2 C6-C 10 Aryl, benzyl, one or more R a Substituted C1-C6 alkyl, 5-10 membered heteroaryl, substituted by one or more R f substituted 5-10 membered heteroaryl, substituted by one or more R b Substituted C6-C 10 Aryl or one or more R c substituted benzyl;

[0093] Or, R 1 and R 2 Together with the nitrogen atom therebetween, it forms a 3-7 membered heterocyclic ring or is replaced by one or more R e A substituted 3-7 membered heterocycle; when there are multiple substituents, the substituents are the same or different;

[0094] The 3-7 membered heterocyclic ring is represented by one or more R e The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of the heteroatom is 1 to 4;

[0095] The 5-10 membered heteroaryl group and one or more R f The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of the heteroatoms is 1 to 4;

[0096] Each R a are independently benzyl, C2-C6 alkynyl or R a-1 is a C1-C6 alkyl group;

[0097] Each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocycle, or substituted by one or more R b-5 substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R b-5 The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of the heteroatom is 1 to 4;

[0098] Each R c are independently halogen;

[0099] Each R e Independently C6-C 10 Aryl or one or more R e-1 Substituted C6-C 10Aryl; when there are multiple substituents, the substituents are the same or different;

[0100] Each R f are independently halogen;

[0101] Each R b-5 are independently hydrogen, or C1-C6 alkyl;

[0102] Each R e-1 It is independently a C1-C6 alkyl group substituted by one or more halogens; when there are multiple substituents, the substituents are the same or different.

[0103] In one plan,

[0104] R 3 C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, 5-10 membered heteroaryl or one or more R 1-8 substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1-8 The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4;

[0105] Each R 1-1 are independently halogen, nitro, cyano, C2-C6 alkynyl, C(O)OR 1-1-1 、C(O)R 1-1-2 NR 1-1-3 C(O)R 1-1-4 , C 1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR 1-1-5 ;

[0106] Each R 1-8 are independently halogen, C 1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR 1-1-5 ;

[0107] Each R 1-1-1 Independently for C 1-10 alkyl;

[0108] Each R 1-1-2 Independently for C 1-10 alkyl;

[0109] Each R 1-1-3 and R 1-1-4 are independently hydrogen or C1-10 alkyl;

[0110] Each R 1-1-5 Independently for C 1-10 alkyl;

[0111] Each R 1-1-13 are independently hydroxyl.

[0112] In one embodiment, the application

[0113] R 1 is H;

[0114] R 2 C6-C 10 Aryl, one or more R a Substituted C1-C6 alkyl, 5-10 membered heteroaryl, substituted by one or more R f substituted 5-10 membered heteroaryl or one or more R b Substituted C6-C 10 Aryl;

[0115] Or, R 1 and R 2 Together with the nitrogen atom therebetween, they form a 3-7 membered heterocyclic ring;

[0116] The heteroatoms in the 3-7 membered heterocyclic ring are selected from one or two of N, O or S, and the number of heteroatoms is 1 to 2;

[0117] The 5-10 membered heteroaryl group and one or more R f The heteroatom in the substituted 5-10 membered heteroaryl group is selected from one or two of N, O and S, and the number of the heteroatom is 1 to 2;

[0118] Each R a are independently benzyl, or R a-1 is a C1-C6 alkyl group;

[0119] Each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocycle, or substituted by one or more R b-5 substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R b-5 The heteroatoms in the substituted 3-7 membered heterocyclic ring are selected from one or two of N, O and S, and the number of heteroatoms is 1 to 4;

[0120] Each R b-5are independently hydrogen, or C1-C6 alkyl;

[0121] Each R f are independently halogen.

[0122] In one plan,

[0123] R 3 C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, 5-10 membered heteroaryl or one or more R 1-8 substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1-8 The heteroatom in the substituted 5-10 membered heteroaryl group is selected from one or two of N, O and S, and the number of the heteroatom is 1 to 2;

[0124] Each R 1-1 are independently halogen, nitro, C2-C6 alkynyl, C(O)R 1-1-2 , C 1-6 Alkyl, with one or more R 1-1-13 Substituted C 1-6 Alkyl, or OR 1-1-5 ;

[0125] Each R 1-8 are independently halogen, C 1-6 Alkyl, with one or more R 1-1-13 Substituted C 1-6 Alkyl, or OR 1-1-5 ;

[0126] Each R 1-1-2 Independently for C 1-6 alkyl;

[0127] Each R 1-1-5 Independently for C 1-6 alkyl;

[0128] Each R 1-1-13 are independently hydroxyl.

[0129] In one plan,

[0130] R 1 is H;

[0131] R 2 C6-C 10 Aryl, benzyl, one or more R a Substituted C1-C6 alkyl, 5-10 membered heteroaryl, substituted by one or more R f substituted 5-10 membered heteroaryl, substituted by one or more Rb Substituted C6-C 10 Aryl or one or more R c Substituted benzyl, or, R 1 and R 2 Together with the nitrogen atom therebetween, it forms a 3-7 membered heterocyclic ring or is replaced by one or more R e substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R e The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; the 5-10 membered heteroaryl and the one or more R f The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; preferably, R 2 C6-C 10 Aryl, one or more R a Substituted C1-C6 alkyl, 5-10 membered heteroaryl, substituted by one or more R f substituted 5-10 membered heteroaryl or one or more R b Substituted C6-C 10 Aryl; or, R 1 and R 2 Together with the nitrogen atom therebetween, a 3-7 membered heterocyclic ring is formed; the heteroatoms in the 3-7 membered heterocyclic ring are selected from one or two of N, O or S, and the number of heteroatoms is 1 to 2; the 5-10 membered heteroaryl group and the one or more R f The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or two of N, O and S, and the number of the heteroatoms is 1 to 2.

[0132] In one scheme, each R a are independently benzyl, C2-C6 alkynyl or

[0133] In one scenario, R a-1 It is a C1-C6 alkyl group.

[0134] In one scheme, each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocycle, or substituted by one or more R b-5 substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R b-5The heteroatoms in the substituted 3-7 membered heterocyclic ring are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; preferably, each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocycle, or substituted by one or more R b-5 substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R b-5 The heteroatoms in the substituted 3-7 membered heterocyclic ring are selected from one or two of N, O and S, and the number of the heteroatoms is 1 to 4.

[0135] In one scheme, each R c are independently halogen.

[0136] In one scheme, each R f are independently halogen.

[0137] In one scheme, each R b-5 are independently hydrogen, Or C1-C6 alkyl.

[0138] In one scenario, R 3 C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, 5-10 membered heteroaryl or one or more R 1-8 substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1-8 The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; preferably, R 3 C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, 5-10 membered heteroaryl or one or more R 1-8 substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1-8 The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or two of N, O and S, and the number of the heteroatoms is 1 to 2.

[0139] In one scheme, each R 1-1 are independently halogen, nitro, cyano, C2-C6 alkynyl, C(O)OR 1-1-1 、C(O)R 1 -1-2 NR 1-1-3 C(O)R 1-1-4 , C1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR 1-1-5 Preferably, each R 1-1 are independently halogen, nitro, C2-C6 alkynyl, C(O)R 1-1-2 , C 1-6 Alkyl, with one or more R 1-1-13 Substituted C 1-6 Alkyl, or OR 1-1-5 .

[0140] In one scheme, each R 1-8 are independently halogen, C 1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR 1-1-5 Preferably, each R 1-8 are independently halogen, C 1-6 Alkyl, with one or more R 1-1-13 Substituted C 1-6 Alkyl, or OR 1-1-5 .

[0141] In one scheme, each R 1-1-1 Independently for C 1-10 alkyl.

[0142] In one scheme, each R 1-1-2 Independently for C 1-10 Alkyl; preferably, each R 1-1-2 Independently for C 1-6 alkyl.

[0143] In one scheme, each R 1-1-3 and R 1-1-4 are independently hydrogen or C 1-10 alkyl.

[0144] In one scheme, each R 1-1-5 Independently for C 1-10 Alkyl; preferably, each R 1-1-5 Independently for C 1-6 alkyl.

[0145] In one scheme, each R 1-1-13 are independently hydroxyl.

[0146] In one scenario, R 1 and R 2 In the above, the C1-C6 alkyl group may be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl, for example, methyl, ethyl or n-butyl.

[0147] In one scenario, R 1 and R 2 In the C6-C 10 Aryl may be phenyl or naphthyl, for example phenyl.

[0148] In one scenario, R 1 and R 2 wherein the 4-7 membered heterocyclic ring is C6-C 10 C6-C in aromatic groups 10 The aryl group may be phenyl.

[0149] In one scenario, R 1 and R 2 wherein the 4-7 membered heterocyclic ring is C6-C 10 The 4-7-membered heterocyclic ring in the aryl group may be a 5-6-membered heterocyclic ring, for example, a 5-membered heterocyclic ring.

[0150] In one scenario, R 1 and R 2 wherein the 4-7 membered heterocyclic ring is C6-C 10 The heteroatom of the 4-7 membered heterocyclic ring in the aryl group may be N, and the number of the heteroatoms may be 1 to 2, for example, 1.

[0151] In one scheme, when R 1 and R 2 Together with the nitrogen atoms in between, they form a e When the 3-7 membered heterocyclic ring is substituted, the ring is replaced by one or more R e The 3- to 7-membered heterocycle in the substituted 3- to 7-membered heterocycle may be a 5- to 6-membered heterocycle, for example, a 6-membered heterocycle.

[0152] In one embodiment, the application, when R 1 and R 2 Together with the nitrogen atoms in between, they form a e When the 3-7 membered heterocyclic ring is substituted, the ring is replaced by one or more R e The heteroatom of the 3- to 7-membered heterocyclic ring in the substituted 3- to 7-membered heterocyclic ring may be N, and the number of the heteroatoms may be 1 to 2, for example, 2.

[0153] In one scenario, R a In the above, the C2-C6 alkynyl group may be an ethynyl group.

[0154] In one scenario, R a-1 In the above, the C1-C6 alkyl group may be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl, for example, methyl, ethyl or n-butyl.

[0155] In one scenario, R bIn the above, the C2-C6 alkynyl group may be an ethynyl group.

[0156] In one scenario, R b In the above, the halogen may be fluorine, chlorine, bromine or iodine.

[0157] In one scenario, R b In the above, the C1-C6 alkyl group substituted by one or more hydroxyl groups may be a methyl group, an ethyl group, a n-propyl group or an isopropyl group, for example a methyl group.

[0158] In one scenario, R b In the above, the C1-C6 alkyl group substituted by one or more halogens may be a methyl group, an ethyl group, a n-propyl group or an isopropyl group, for example a methyl group.

[0159] In one scenario, R b In the above, the halogen in the C1-C6 alkyl substituted by one or more halogens may be fluorine, chlorine or bromine, for example fluorine.

[0160] In one scenario, R b In the above, the C1-C6 alkyl group substituted by one or more halogens is trifluoromethyl.

[0161] In one scenario, R b In the above, the 3-7 membered heterocycle may be a 5-6 membered heterocycle, for example, a 6 membered heterocycle.

[0162] In one scenario, R b In the 3-7 membered heterocyclic ring, the heteroatom may be N, and the number of heteroatoms may be 1 to 2, for example 2

[0163] In one scenario, R c In the above, the halogen may be fluorine, chlorine, bromine or iodine, for example iodine.

[0164] In one scenario, R d In the embodiment, the 4-7 membered lactam-containing heterocycloalkyl group is a 5-6 membered lactam-containing heterocycloalkyl group, for example, a 6 membered lactam-containing heterocycloalkyl group, and for example,

[0165] In one scenario, R e In the C6-C 10 Aryl may be phenyl or naphthyl, for example phenyl.

[0166] In one scenario, R c In the embodiment of the present invention, the halogen may be fluorine, chlorine, bromine or iodine, for example iodine.

[0167] In one scenario, R b-1 In the above, the C1-C6 alkane is methyl, ethyl, n-propyl or isopropyl, for example methyl.

[0168] In one scheme, when R b-2 and R b-3 When the nitrogen atom therebetween forms a 3-7 membered heterocycle substituted by one or more C1-C6 alkyl groups, the 3-7 membered heterocycle in the 3-7 membered heterocycle substituted by one or more C1-C6 alkyl groups may be a 5-6 membered heterocycle, for example a 6 membered heterocycle.

[0169] In one scheme, when R b-2 and R b-3 When together with the nitrogen atom therebetween, a 3-7 membered heterocyclic ring substituted by one or more C1-C6 alkyl groups is formed, the heteroatom of the 3-7 membered heterocyclic ring in the 3-7 membered heterocyclic ring substituted by one or more C1-C6 alkyl groups may be N, and the number of heteroatoms may be 1 to 2, for example 2.

[0170] In one scheme, when R b-2 and R b-3 When together with the nitrogen atom therebetween, they form a 3-7 membered heterocyclic ring substituted by one or more C1-C6 alkyl groups, the C1-C6 alkyl groups may be methyl, ethyl, n-propyl or isopropyl, for example methyl.

[0171] In one scenario, R b-4 In the above, the 5-10 membered heteroaryl group may be a 5-6 membered heteroaryl group, for example, a 6 membered heteroaryl group.

[0172] In one scenario, R b-4 In the 5-10 membered heteroaryl group, the heteroatom of the 5-10 membered heteroaryl group may be N, and the number of the heteroatoms may be 1 to 2, for example, 2.

[0173] In one scenario, R b-5 In the above, the C1-C6 alkyl group may be methyl, ethyl, n-propyl or isopropyl, for example methyl.

[0174] In one scenario, R b-6 In the above, the C1-C6 alkoxy group may be a methoxy group, an ethoxy group, a n-propoxy group or an isopropoxy group, for example a methoxy group.

[0175] In one scenario, R e-1 In the above, the C1-C6 alkyl group substituted by one or more halogens may be a methyl group, an ethyl group, a n-propyl group or an isopropyl group.

[0176] In one scenario, R e-1 In the above, the halogen in the C1-C6 alkyl substituted by one or more halogens may be fluorine, chlorine or bromine, for example fluorine.

[0177] In one scenario, R e-1In the above, the C1-C6 group substituted by one or more halogens is a trifluoromethyl group.

[0178] In one embodiment, R 3 In the C 1-10 The alkyl group is preferably C 1-6 Alkyl, more preferably C 1-4 The alkyl group is more preferably a methyl group, an ethyl group, a n-propyl group, an isopropyl group or an isobutyl group.

[0179] In one embodiment, R 3 In the C 6-14 The aryl group is preferably C 6-12 The aryl group is more preferably a phenyl group or a naphthyl group.

[0180] In one embodiment, R 3 In the above, the 5-12 membered heterocycloalkyl is preferably a 5-10 membered heterocycloalkyl, more preferably a 5-6 membered heterocycloalkyl, further preferably a piperazinyl, pyrrolidinyl or pyridinyl.

[0181] In one embodiment, R 3 In the 5-10 membered heteroaryl group, the heteroatom may be N, and the number of heteroatoms may be 1 to 2, for example

[0182] In one embodiment, R 3 In the C 5-20 Cycloalkyl C 6-14 The aryl group is preferably C 5-16 Cycloalkyl C 6-12 Aryl, more preferably C 5-14 Cycloalkylphenyl, more preferably

[0183] In one embodiment, each R 1-1 In the above, the halogen may be fluorine, chlorine, bromine or iodine.

[0184] In one embodiment, each R 1-1 In the above, the C2-C6 alkynyl group may be an ethynyl group.

[0185] In one embodiment, each R 1-1 In, C 1-10 The alkyl group is preferably C 1-6 Alkyl, more preferably C 1-4 The alkyl group is more preferably a methyl group, an ethyl group, a n-propyl group, an isopropyl group or an isobutyl group.

[0186] In one embodiment, each R 1-8 In the above, the halogen may be fluorine, chlorine, bromine or iodine.

[0187] In one embodiment, each R 1-8 In, C 1-10 The alkyl group is preferably C 1-6 Alkyl, more preferably C 1-4 The alkyl group is more preferably a methyl group, an ethyl group, a n-propyl group, an isopropyl group or an isobutyl group.

[0188] In one embodiment, each R 1-1-2 In, C 1-10 The alkyl group is preferably C 1-6 Alkyl, more preferably C 1-4 The alkyl group is more preferably a methyl group, an ethyl group, a n-propyl group, an isopropyl group or an isobutyl group.

[0189] In one embodiment, each R 1-1-5 In, C 1-10 The alkyl group is preferably C 1-6 Alkyl, more preferably C 1-4 The alkyl group is more preferably a methyl group, an ethyl group, a n-propyl group, an isopropyl group or an isobutyl group.

[0190] In one embodiment, R 1 is hydrogen; R 2 for

[0191] or, for

[0192] In one embodiment, R 3 for

[0193] In one embodiment, R 1 is hydrogen; R 2 for or, for In one embodiment, R 3 for

[0194] In a certain embodiment, the application, the compound shown in formula C is any of the following compounds:

[0195]

[0196] In a certain embodiment, the application, the compound shown in formula D is any of the following compounds:

[0197]

[0198] In the present invention, the method for preparing the compound as shown in Formula 1 may further include the following steps: in the presence of a base, compound 2 and sulfuryl fluoride (SO2F2) react in a solvent to obtain fluorosulfonylguanidine as shown in Formula 1.

[0199] The preparation conditions and operation of the fluorosulfonylguanidine as shown in Formula 1 are the same as those described in the previous item.

[0200] The present invention provides a compound as shown in formula C,

[0201]

[0202] R 1 and R 2 The definition of is as mentioned above.

[0203] The present invention provides a compound as shown in formula D,

[0204]

[0205] R 3 The definition of is as mentioned above.

[0206] Unless otherwise specified, the terms used in the present invention have the following meanings:

[0207] In the present invention, the term "heterocycle" used refers to a ring with a specified number of ring atoms (e.g., 5 to 10 members), a specified number of heteroatoms (e.g., 1, 2 or 3), and a specified heteroatom type (one or more of N, O and S), which is a monocyclic, bridged or spirocyclic ring. Heterocycles include, but are not limited to, azetidine, tetrahydropyrrole, tetrahydrofuran, morpholine, piperidine, piperazine, and the like.

[0208] In the present invention, the term "heterocycloalkyl" used refers to a cyclic group having a specified number of ring atoms (e.g., 5 to 10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified heteroatom type (one or more of N, O, and S), which is a monocyclic, bridged, or spirocyclic ring, and each ring is saturated. Heterocycloalkyl includes, but is not limited to, azetidinyl, tetrahydropyrrolyl, tetrahydrofuranyl, morpholinyl, piperidinyl, and the like.

[0209] In the present invention, the term "heteroaryl" used refers to a cyclic group with a specified number of ring atoms (e.g., 5 to 10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified heteroatom type (one or more of N, O, and S), which is monocyclic or polycyclic, and at least one ring is aromatic (in accordance with Huckel's rule). The heteroaryl group is connected to other fragments in the molecule through an aromatic ring or a non-aromatic ring. Heteroaryl includes, but is not limited to, furanyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl, and the like.

[0210] As used herein, the term "hydroxyl" refers to an -OH group.

[0211] As used herein, the term "carboxyl" refers to a -COOH group.

[0212] In the present invention, the "C x1 -C y1 " (x1 and y1 are integers), such as "C x1 -C y1 "Alkyl, "C x1 -C y1 "alkoxy", "C x1 -C y1 "Alkynyl, "C x1 -C y1 "Aryl, "C x1 -C y1 "Benzyl" means the number of carbon atoms not including the substituents, for example, C1-C6 alkyl means C1-C6 alkyl not including the substituents.

[0213] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0214] The reagents and raw materials used in the present invention are commercially available.

[0215] The positive progress of the present invention is that it provides a fluorosulfonylguanidine, which can convert amine and phenol compounds into aminosulfonylguanidine and guanidinium sulfonate compounds under mild conditions, simple operation, and easy to scale up process, and has good substrate universality. The preparation method of the fluorosulfonylguanidine has mild conditions, simple process, and is easy to scale up production. The aminosulfonylguanidine and guanidinium sulfonate compounds have potential antiviral and antitumor effects and have great commercial and medical value. DETAILED DESCRIPTION

[0216] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0217] Experimental instruments:

[0218] 1 H NMR spectra were measured using an Agilent-400 (400 MHz) nuclear magnetic resonance spectrometer. 1 The internal standard for H NMR was TMS (δ 0.00) or DMSO-d6 (δ 2.50).

[0219] 13 C NMR spectra were measured using a Bruker AM-400 (100.7 MHz) nuclear magnetic resonance spectrometer. 13 The internal standards for C NMR were DMSO-d6 (39.52) and CD3CN (δ1.32).

[0220] 19 F NMR spectra were measured using an Agilent-400 (376 MHz) nuclear magnetic resonance spectrometer. 19 The external standard for F NMR was FCCl3 (δ 0.00), positive downfield.

[0221] LC-MS (ESI) spectra were measured using a Waters ACQUITY UPLC H-Class system and an ACQUITY QDa mass spectrometer detector (eluents: 0.1% trifluoroacetic acid in water and acetonitrile).

[0222] HRMS spectra were measured using a Thermo Scientific LTQ FT Ultra FT-MS mass spectrometer.

[0223] The melting point was determined using a BUCHI M-565 melting point apparatus.

[0224] Experimental reagents and materials:

[0225] Column chromatography used silica gel (300-400 mesh or 100-200 mesh) produced by Yantai Jiangyou Silica Gel Development Co., Ltd.; thin layer chromatography plates used thin layer chromatography plates produced by Yantai Jiangyou Silica Gel Development Co., Ltd., and color development tools included ZF-7A portable UV detector, iodine cylinder, and alkaline potassium permanganate solution.

[0226] The reagents used were purchased from Shanghai Aladdin Biochemical Technology Co., Ltd. (Aladdin), Tokyo Chemical Industry Development Co., Ltd. (TCI), Shanghai Macklin Biochemical Technology Co., Ltd. (Macklin), San Chemical Technology (Shanghai) Co., Ltd. (Energy Chemical), Alfa Aesar (China) Chemical Co., Ltd. (Alfa Aesar), Shanghai Titan Technology Co., Ltd. (adamas), Shanghai Bid Pharmaceutical Technology Co., Ltd., Shanghai Tianlian Chemical Technology Co., Ltd., Shanghai Lingfeng Chemical Reagent Co., Ltd. or Shanghai Reagent Factory No. 3.

[0227] The solvents were purchased from Shanghai Macklin Biochemical Technology Co., Ltd. (Macklin), Shanghai Titan Technology Co., Ltd. (adamas), Shanghai Tianlian Chemical Technology Co., Ltd., Shanghai Dahe Chemical Co., Ltd., and Shanghai Hebang Pharmaceutical Technology Co., Ltd. and were used directly after purchase without additional treatment.

[0228] Example 1 Preparation of Fluorosulfonylguanidine

[0229]

[0230] Guanidine hydrochloride (10.8 g, 113 mmol) was added to the reactor, and then N,N-dimethylformamide (50 mL) and triethylamine (31 mL, 226 mmol) were added. The reaction system was pumped to negative pressure by a water pump, stirred at room temperature for ten minutes, and sulfuryl fluoride gas (7.7 g, 75 mmol) was introduced by a balloon, and stirred at 50°C for 5 hours until the balloon was completely deflated. 200 mL of water was added to the reactor to quench the reaction, and the aqueous phase was extracted with ethyl acetate (3×250 mL). The organic phases were combined and washed with saturated brine (2×100 mL), and concentrated on a rotary evaporator to obtain a crude product. The crude product was dissolved in 40 mL of water, and then the aqueous phase was extracted with ethyl acetate (3×25 mL). The organic phases were combined and washed with 25 mL of saturated brine, dried over anhydrous sodium sulfate, and filtered to obtain a filtrate. The filtrate was concentrated on a rotary evaporator and then slurried with 120 mL of a mixed solution of ethyl acetate / dichloromethane / petroleum ether (v / v / v=1:1:2) at room temperature for 15 minutes. A white solid precipitated, which was filtered and washed with 100 mL of dichloromethane to obtain the final product, fluorosulfonylguanidine (5.7 g, total yield 54%), a white solid, purity: 95%, melting point: 168-169°C. 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.19 (s, 4H). 13 C NMR (126 MHz, deuterated dimethyl sulfoxide) δ 158.77. 19 F NMR (376 MHz, deuterated dimethyl sulfoxide) δ 53.74. HRMS (ESI) m / z [M+H] +:calcd.142.0081,found 142.0081.

[0231] Example 2 Screening of reaction conditions for preparing fluorosulfonylguanidine (compound 1) by reacting guanidine hydrochloride (compound 2) with sulfuryl fluoride gas

[0232] Except for the conditions specifically indicated in Table 1 below, the remaining conditions and operations are the same as those described in Example 1 for preparing fluorosulfonylguanidine (the compound shown in Formula 1) by reacting guanidine hydrochloride (Compound 2) with sulfuryl fluoride gas.

[0233] Table 1 Screening of reaction conditions for preparing fluorosulfonylguanidine

[0234]

[0235] Note: The equivalent of the base in Table 1 is relative to the amount of guanidine hydrochloride.

[0236] Example 3 Synthesis of N-(phenyl)aminosulfonylguanidine

[0237]

[0238] Fluorosulfonylguanidine (141.1 mg, 1 mmol), triethylenediamine (DABCO) (112.2 mg, 1 mmol), water (2.5 mL) and aniline (46 μL, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. After quenching with 5 mL of water, the aqueous phase was extracted with ethyl acetate (4×10 mL), and the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated with a rotary evaporator and passed through a column (dichloromethane / methanol, v / v=10:1) to obtain white solid N-(phenyl)aminosulfonylguanidine (95 mg, yield 88%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 9.17 (s, 1H), 7.21–7.17 (m, 2H), 7.10–7.08 (m, 2H), 6.91–6.87 (m, 1H), 6.56 (s, 4H).

[0239] Example 4 Synthesis of N-(4-chlorophenyl)aminosulfonylguanidine

[0240]

[0241] Fluorosulfonylguanidine (141.1 mg, 1 mmol), triethylenediamine (DABCO) (112.2 mg, 1 mmol), water (2.5 mL) and 4-chloroaniline (63.8 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. After quenching with 5 mL of water, the aqueous phase was extracted with ethyl acetate (4×10 mL), and the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by rotary evaporator and passed through a column (dichloromethane / methanol, v / v=10:1) to obtain white solid N-(4-chlorophenyl)aminosulfonylguanidine (99 mg, yield 80%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 9.33 (s, 1H), 7.26 (d, J = 8.9 Hz, 2H), 7.10 (d, J = 8.9 Hz, 2H), 6.58 (s, 4H).

[0242] Example 5 Synthesis of N-(4-iodophenyl)aminosulfonylguanidine

[0243]

[0244] Fluorosulfonylguanidine (141.1 mg, 1 mmol), triethylenediamine (DABCO) (112.2 mg, 1 mmol), water (2.5 mL) and 4-iodoaniline (109.5 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. After quenching with 5 mL of water, the aqueous phase was extracted with ethyl acetate (4×10 mL), and the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by rotary evaporator and passed through a column (dichloromethane / methanol, v / v=10:1) to obtain gray solid N-(4-iodophenyl)aminosulfonylguanidine (113 mg, yield 67%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 9.33 (s, 1H), 7.52 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 6.59 (s, 4H).

[0245] Example 6 Synthesis of N-(3-ethynylphenyl)aminosulfonylguanidine

[0246]

[0247] Fluorosulfonylguanidine (141.1 mg, 1 mmol), triethylenediamine (DABCO) (112.2 mg, 1 mmol), water (2.5 mL) and 3-ethynylaniline (56 μL, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-(3-ethynylphenyl)aminosulfonylguanidine (91 mg, yield 77%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 9.35 (s, 1H), 7.23–7.19 (m, 2H), 7.11–7.08 (m, 1H), 7.00 (d, J=7.5 Hz, 1H), 6.60 (s, 4H), 4.12 (s, 1H).

[0248] Example 7 Synthesis of N-(3-methoxyphenyl)aminosulfonylguanidine

[0249]

[0250] Fluorosulfonylguanidine (141.1 mg, 1 mmol), triethylenediamine (DABCO) (112.2 mg, 1 mmol), water (2.5 mL) and 3-methoxyaniline (56 μL, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. After quenching with 5 mL of water, the aqueous phase was extracted with ethyl acetate (4×10 mL), and the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated with a rotary evaporator and passed through a column (dichloromethane / methanol, v / v=10:1) to obtain a light pink solid N-(3-methoxyphenyl)aminosulfonylguanidine (112 mg, yield 92%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 9.15 (s, 1H), 7.09 (t, J = 8.1 Hz, 1H), 6.70 (t, J = 2.2 Hz, 1H), 6.67–6.64 (m, 1H), 6.57 (s, 4H), 6.49–6.46 (m, 1H), 3.68 (s, 3H).

[0251] Example 8 Synthesis of N-(5-bromopyridin-3-yl)aminosulfonylguanidine

[0252]

[0253] Fluorosulfonylguanidine (141.1 mg, 1 mmol), triethylenediamine (DABCO) (112.2 mg, 1 mmol), water (2.5 mL) and 5-bromopyridin-3-amine (86.5 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. After quenching with 5 mL of water, the aqueous phase was extracted with ethyl acetate (4×10 mL), and the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated by rotary evaporator and passed through a column (dichloromethane / methanol, v / v=10:1) to obtain white solid N-(5-bromopyridin-3-yl)aminosulfonylguanidine (60 mg, yield 41%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 9.75 (s, 1H), 8.27 (d, J = 2.3 Hz, 1H), 8.22 (d, J = 2.1 Hz, 1H), 7.70–77.69 (m, 1H), 6.71 (s, 4H).

[0254] Example 9 Synthesis of 4-phenyl-1-piperazinesulfonylguanidine

[0255]

[0256] Fluorosulfonylguanidine (141.1 mg, 1 mmol), triethylenediamine (DABCO) (112.2 mg, 1 mmol), water (2.5 mL) and N-phenylpiperazine (77 μL, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. After quenching with 5 mL of water, the aqueous phase was extracted with ethyl acetate (4×10 mL), and the organic phase was washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated with a rotary evaporator and passed through a column (dichloromethane / methanol, v / v=10:1) to obtain 4-phenyl-1-piperazinesulfonylguanidine (128 mg, yield 90%) as a white solid. 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.25–7.19 (m, 2H), 6.98–6.92 (m, 2H), 6.80 (t, J = 7.3 Hz, 1H), 6.59 (s, 4H), 3.22–3.15 (m, 4H), 3.09–3.02 (m, 4H).

[0257] Example 10 Synthesis of N-(Carbamimidoylaminosulfonyl)-L-phenylalanine tert-butyl ester

[0258]

[0259] Fluorosulfonylguanidine (141.1 mg, 1 mmol), triethylenediamine (DABCO) (112.2 mg, 1 mmol), water (2.5 mL) and N-phenylpiperazine (77 μL, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-(amidinoaminosulfonyl)-L-phenylalanine tert-butyl ester (105 mg, yield 61%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.29–7.25 (m, 2H), 7.22–7.17 (m, 3H), 6.45 (s, 4H), 6.43 (s, 1H), 3.87–3.81 (m, 1H), 2.96–2.91 (m, 1H), 2.82–2.76 (m, 1H), 1.24 (s, 9H).

[0260] Example 11 Synthesis of N-(amidinoaminosulfonyl)-amlodipine

[0261]

[0262] Fluorosulfonylguanidine (141.1 mg, 1 mmol), triethylenediamine (DABCO) (112.2 mg, 1 mmol), water (2.5 mL) and amlodipine (204.4 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-(amidinoaminosulfonyl)-amlodipine (193 mg, yield 73%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ8.49 (s, 1H), 7.35–7.33 (m, 1H), 7.27–7.20 (m, 2H), 7.15–7.10 (m, 1H), 6.48–6.43 (m, 4H), 5.29 (s, 1H), 4.64–4.51 (m, 2H), 3.99–3.92 (m, 2H), 3.53–3.50 (m, 5H), 3.02 (d, J = 5.8 Hz, 2H), 2.30 (s, 3H), 1.10 (t, J = 7.1 Hz, 3H).

[0263] Example 12 Synthesis of N-formamidinylaminosulfonic acid phenol ester

[0264]

[0265] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and phenol (44 μL, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-carboxamidosulfonic acid phenol ester (86 mg, yield 80%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.44–7.35 (m, 2H), 7.30–7.12 (m, 3H), 6.91 (s, 4H).

[0266] Example 13 Synthesis of N-carboxamidosulfonic acid-(4-fluorophenol)-ester

[0267]

[0268] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and 4-fluorophenol (56.1 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-carboxamidosulfonic acid-(4-fluorophenol)-ester (111 mg, yield 96%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) -δ7.24–7.22 (m, 4H), 6.92 (s, 4H). 19 F NMR (376 MHz, deuterated dimethyl sulfoxide) δ-117.10.

[0269] Example 14 Synthesis of N-carboxamidosulfonic acid-(4-bromophenol)-ester

[0270]

[0271] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and 4-bromophenol (86.5 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-carboxamidosulfonic acid-(4-bromophenol)-ester (138 mg, yield 94%). 1H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.61–7.57 (m, 2H), 7.19–7.15 (m, 2H), 6.94 (s, 4H).

[0272] Example 15 Synthesis of N-carboxamidosulfonic acid-(4-methoxyphenol)-ester

[0273]

[0274] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and 4-methoxyphenol (62.1 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-carboxamidosulfonic acid-(4-methoxyphenol)-ester (104 mg, yield 85%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.13–7.09 (m, 2H), 6.94–6.90 (m, 2H), 6.87 (s, 4H), 3.74 (s, 3H).

[0275] Example 16 Synthesis of N-carboxamidosulfonic acid-(4-nitrophenol)-ester

[0276]

[0277] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and 4-nitrophenol (69.6 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-carboxamidosulfonic acid-(4-nitrophenol)-ester (118 mg, yield 91%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 8.31–8.27 (m, 2H), 7.49–7.45 (m, 2H), 7.04 (s, 4H).

[0278] Example 17 Synthesis of N-carboxamidosulfonic acid-(3-acetylphenol)-ester

[0279]

[0280] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and 3-acetylphenol (68.1 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-carboxamidosulfonic acid-(3-acetylphenol)-ester (82 mg, yield 64%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.86 (d, J = 7.6 Hz, 1H), 7.73–7.72 (t, J = 2.1 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.49–7.46 (m, 1H), 6.96 (s, 4H), 2.58 (s, 3H).

[0281] Example 18 Synthesis of N-carboxamidosulfonic acid-(3-ethynylphenol)-ester

[0282]

[0283] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and 3-ethynylphenol (54.5 μL, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-carboxamidosulfonic acid-(3-ethynylphenol)-ester (116 mg, yield 97%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.43–7.35 (m, 2H), 7.31–7.24 (m, 2H), 6.96 (s, 4H), 4.27 (s, 1H).

[0284] Example 19 Synthesis of N-carboxamidosulfonic acid-(1-bromophenol)-ester

[0285]

[0286] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and 1-bromophenol (58 μL, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-carboxamidosulfonic acid-(1-bromophenol)-ester (140 mg, yield 95%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.68–7.66 (m, 1H), 7.49–7.47 (m, 1H), 7.42–7.38 (m, 1H), 7.19–7.15 (m, 1H), 7.01 (s, 4H).

[0287] Example 20 Synthesis of N-formamidinylaminosulfonic acid-(4-hydroxyethylphenol)-ester

[0288]

[0289] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and 4-hydroxyethylphenol (69.1 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain white solid N-carboxamidosulfonic acid-(4-hydroxyethylphenol)-ester (125 mg, yield 96%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 7.22 (d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.5 Hz, 2H), 6.89 (s, 4H), 4.65 (t, J = 5.2 Hz, 1H), 3.59 (td, J = 7.0, 5.2 Hz, 2H), 2.70 (t, J = 7.0 Hz, 2H).

[0290] Example 21 Synthesis of N-carboxamidosulfonic acid-(α-naphthol)-ester

[0291]

[0292] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and α-naphthol (72.1 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain a light pink solid N-carboxamidosulfonic acid-(α-naphthol)-ester (122 mg, yield 92%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 8.15–8.12 (m, 1H), 7.97–7.94 (m, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.59–7.48 (m, 4H), 6.98 (s, 4H).

[0293] Example 22 Synthesis of N-carboxamidosulfonic acid-(3,4-methylenedioxyphenol)-ester

[0294]

[0295] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and sesamol (69.1 mg, 0.5 mmol) were added to the reaction vessel and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, washed with water (3×2.5 mL), and the precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain colorless solid N-carboxamidosulfonic acid-(3,4-methylenedioxyphenol)-ester (117 mg, yield 90%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 6.90–6.88 (m, 5H), 6.78 (d, J = 2.4 Hz, 1H), 6.65 (dd, J = 8.4, 2.4 Hz, 1H), 6.04 (s, 2H).

[0296] Example 23 Synthesis of N-carbamimidylsulfamate-(scopolamine)-ester

[0297]

[0298] Fluorosulfonylguanidine (105.8 mg, 0.75 mmol), triethylenediamine (DABCO) (84.1 mg, 0.75 mmol), water (2.5 mL) and scopolamine (96.1 mg, 0.5 mmol) were added to the reaction vessel, and stirred at 70°C for 12 hours. The mixture was quenched with 5 mL of water, filtered, and washed with water (3×2.5 mL). The precipitate was dissolved in acetonitrile, dried by rotary evaporation, and dried to obtain colorless solid N-carboxamidosulfonic acid-(scopolamine)-ester (117 mg, yield 90%). 1 H NMR (400 MHz, deuterated dimethyl sulfoxide) δ 8.01 (d, J = 9.6 Hz, 1H), 7.44 (s, 1H), 7.32 (s, 1H), 7.03 (s, 4H), 6.47 (d, J = 9.6 Hz, 1H), 3.83 (s, 3H).

Claims

1. Use of a fluorosulfonylguanidine as shown in Formula 1 in the preparation of a guanidine compound, 2. The use according to claim 1, characterized in that: In a solvent, the fluorosulfonylguanidine as shown in Formula 1 and the The amine compound containing the structural fragment shown in formula A is reacted to obtain a compound containing the structural fragment shown in formula A; In a solvent, the fluorosulfonylguanidine as shown in Formula 1 and the The alcohol-phenol compound containing the structural fragment shown in formula A is reacted to obtain a compound containing the structural fragment shown in formula B; Preferably, it comprises the following steps: In solvent, The formula The amine compound of the structural fragment shown is Obtain a compound as shown in formula C; in, R 1 and R 2 are independently H, C1-C6 alkyl, C6-C 10 Aryl, benzyl, 4-7 membered heterocyclic and C6-C 10 Aryl, 5-10 membered heteroaryl, or one or more R f substituted 5-10 membered heteroaryl, substituted by one or more R a Substituted C1-C6 alkyl, one or more R b Substituted C6-C 10 Aryl, one or more R c substituted benzyl or one or more R d Substituted 4-7 membered heterocyclic C6-C 10 aryl; and R 1 and R 2 are not H at the same time; when there are multiple substituents, the substituents are the same or different; Or, R 1 and R 2 Together with the nitrogen atom therebetween, it forms a 3-7 membered heterocyclic ring or is replaced by one or more R e A substituted 3-7 membered heterocycle; when there are multiple substituents, the substituents are the same or different; The 4-7 membered heterocyclic ring is C6-C 10 Aryl and one or more R d Substituted 4-7 membered heterocyclic C6-C 10 The heteroatom in the aryl group is selected from one or more of N, O and S, and the number of the heteroatom is 1 to 4; The 3-7 membered heterocyclic ring is represented by one or more R e The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of the heteroatom is 1 to 4; The 5-10 membered heteroaryl group and one or more R f The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of the heteroatoms is 1 to 4; Each R a Independently Carboxyl, benzyl, C2-C6 alkynyl, or hydroxyl; R a-1 is a C1-C6 alkyl group; Each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocyclic ring, with one or more R b-5 Substituted 3-7 membered heterocyclic ring, or When there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and the one or more R b-5 The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of the heteroatom is 1 to 4; Each R c are independently halogen; Each R d Independently 4-7 membered lactam-containing heterocyclic alkyl or Substituted 4-7 membered lactam-containing heterocycloalkyl; Each R e Independently C6-C 10 Aryl or one or more R e-1 Substituted C6-C 10 Aryl; when there are multiple substituents, the substituents are the same or different; Each R f are independently halogen; Each R b-1 are independently C1-C6 alkyl; R b-2 and R b-3 are independently C1-C6 alkyl; or, R b-2 and R b-3 Together with the nitrogen atom therebetween, it forms a 3-7 membered heterocyclic ring or a 3-7 membered heterocyclic ring substituted by one or more C1-C6 alkyl groups; the heteroatoms in the 3-7 membered heterocyclic ring are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; when there are multiple substituents, the substituents are the same or different; Each R b-4 is independently a 5-10 membered heteroaryl or is replaced by one or more R b-6 A substituted 5-10 membered heteroaryl group, wherein the 5-10 membered heteroaryl group is a 5-10 membered heteroaryl group having one or more heteroatoms selected from N, O and S, and the number of heteroatoms is 1 to 4; when there are multiple substituents, the substituents are the same or different; Each R b-4 Independently or C1-C6 alkyl; Each R b-5 are independently hydrogen, or C1-C6 alkyl; Each R b-6 are independently C1-C6 alkyl or C1-C6 alkoxy; Each R e-1 is independently a C1-C6 alkyl group substituted by one or more halogens; when there are multiple substituents, the substituents are the same or different; And / or, in a solvent, the The phenolic alcohol compounds of the structural fragments shown are Obtain a compound as shown in formula D; in, R 3 C 1-10 Alkyl, with one or more R 1-0 Substituted C 1-10 Alkyl, C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, C(O)R 1-3 , 5-12 membered heterocycloalkyl, 1-7 substituted 5-12 membered heterocycloalkyl, 5-10 membered heteroaryl, substituted by one or more R 1-8 Substituted 5-10 membered heteroaryl, C 5-20 Cycloalkyl C 6-14 Aryl, or one or more R 1-9 Substituted C 5-20 Cycloalkyl C 6-14 Aryl; the 5-12 membered heterocycloalkyl and one or more R 1-7 The heteroatoms in the substituted 5-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; the 5-10 membered heteroaryl and the substituted one or more R 1-8 The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; Each R 1-0 are independently halogen, nitro, cyano, oxo, C(O)OR 1-1-1 、C(O)R 1-1-2 NR 1-1-3 R 1-1-4 NR 1-1-3 C(O)R 1-1-4 , OR 1-1-5 , C 6-14 Aryl, one or more R 1-1-7 Substituted C 6-14 Aryl, 5-12 membered heterocycloalkyl, 1-1-8 substituted 5-12 membered heterocycloalkyl, 5-10 membered heteroaryl, substituted by one or more R 1-1-9 Substituted 5-10 membered heteroaryl, C 2-12 Alkynyl, with one or more R 1-1-10 Substituted C 2-12 Alkynyl, vinyl, one or more R 1-1-11 Substituted vinyl, or OS(O)2R 1-1-12 ; Each R 1-1 , R 1-7 , R 1-8 and R 1-9 are independently halogen, nitro, cyano, C2-C6 alkynyl, C(O)OR 1 -1-1 、C(O)R 1-1-2 NR 1-1-3 R 1-1-4 NR 1-1-3 C(O)R 1-1-4 , C 1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR 1-1-5 ; Each R 1-3 are independently hydrogen, NR 1-1-3 R 1-1-4 , C 1-10 Alkyl, with one or more R 1-1-6 Substituted C 1-10 Alkyl, C 6-14 Aryl, one or more R 1-1-7 Substituted C 6-14 Aryl, 5-12 membered heterocycloalkyl, 1-1-8 substituted 5-12 membered heterocycloalkyl, 5-10 membered heteroaryl, or substituted by one or more R 1-1-9 substituted 5-10 membered heteroaryl, vinyl, or one or more R 1-1-11 Replaced vinyl; Each R 1-1-1 Independently for C 1-10 Alkyl, with one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl; Each R 1-1-2 Independently for C 1-10 Alkyl, with one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl, vinyl, or one or more R 1-1-1-3 Replaced vinyl; Each R 1-1-3 and R 1-1-4 are independently hydrogen, C 1-10 Alkyl, with one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl; Each R 1-1-5 Independently for C 1-10 Alkyl, or one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl; Each R 1-1-6 are independently halogen, nitro, cyano, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl; Each R 1-1-7 are independently halogen, nitro, cyano, C 1-10 Alkyl, with one or more R 1-1-1-1 Substituted C 1-10 Alkyl, C 6-14 Aryl, or one or more R 1-1-1-2 Substituted C 6-14 Aryl; R 1-1-12 For halogen, C 1-10 Alkyl, or one or more R 1-1-1-1 Substituted C 1-10 alkyl; Each R 1-1-13 are independently hydroxyl groups; Each R 1-1-8 , R 1-1-9 , R 1-1-10 , R 1-1-11 , R 1-1-1-1 and R 1-1-1-2 are independently halogen, nitro, cyano, C 1-4 Alkyl, halo-C 1-4 Alkyl, -OC 1-4 Alkyl, -NH2, vinyl, ethynyl, C 6-12 Aryl, 5-6 membered heterocycloalkyl, or 5-6 membered heteroaryl; The 5-12 membered heterocycloalkyl group and one or more R 1-1-8 The heteroatoms in the substituted 5-12 membered heterocycloalkyl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; the 5-10 membered heteroaryl and the one or more R 1-1-9 The heteroatoms in the substituted 5-10 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; the heteroatoms in the 5-6 membered heterocycloalkyl and 5-6 membered heteroaryl are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4.

3. The use according to claim 2, characterized in that: Wherein the compound represented by formula C or the compound represented by formula D satisfies one or more of the following conditions: (1)R 1 and R 2 wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl, such as methyl, ethyl or n-butyl; (2)R 1 and R 2 In the C6-C 10 Aryl is phenyl or naphthyl, for example phenyl; (3)R 1 and R 2 wherein the 4-7 membered heterocyclic ring is C6-C 10 C6-C in aromatic groups 10 Aryl is phenyl; (4)R 1 and R 2 wherein the 4-7 membered heterocyclic ring is C6-C 10 The 4-7-membered heterocyclic ring in the aryl group is a 5-6-membered heterocyclic ring, for example, a 5-membered heterocyclic ring; (5)R 1 and R 2 wherein the 4-7 membered heterocyclic ring is C6-C 10 The heteroatom of the 4-7 membered heterocyclic ring in the aryl group is N, and the number of heteroatoms is 1 to 2, for example 1; (6)R 1 and R 2 Together with the nitrogen atoms in between, they form a e When the 3-7 membered heterocyclic ring is substituted, the ring is replaced by one or more R e The 3-7-membered heterocycle in the substituted 3-7-membered heterocycle is a 5-6-membered heterocycle, for example, a 6-membered heterocycle; (7)R 1 and R 2 Together with the nitrogen atoms in between, they form a e When the 3-7 membered heterocyclic ring is substituted, the ring is replaced by one or more R e The heteroatom of the 3-7-membered heterocyclic ring in the substituted 3-7-membered heterocyclic ring is N, and the number of the heteroatoms is 1 to 2, for example 2; (8)R a wherein the C2-C6 alkynyl group is an ethynyl group; (9)R a-1 wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl or tert-butyl, such as methyl, ethyl or n-butyl; (10)R b wherein the C2-C6 alkynyl group is an ethynyl group; (11)R b wherein the halogen is fluorine, chlorine, bromine or iodine; (12)R b wherein the C1-C6 alkyl group substituted by one or more hydroxyl groups is methyl, ethyl, n-propyl or isopropyl, for example, methyl; (13)R b wherein the C1-C6 alkyl group substituted by one or more halogens is methyl, ethyl, n-propyl or isopropyl, for example, methyl; (14)R b wherein the halogen in the C1-C6 alkyl substituted by one or more halogens is fluorine, chlorine or bromine, for example fluorine; (15)R b In the above, the 3-7 membered heterocycle is a 5-6 membered heterocycle, for example, a 6 membered heterocycle; (16)R b In the 3-7 membered heterocyclic ring, the heteroatom is N, and the number of heteroatoms is 1 to 2, for example, 2; (17)R c wherein the halogen is fluorine, chlorine, bromine or iodine, for example iodine; (18)R d In the embodiment, the 4-7 membered lactam-containing heterocycloalkyl group is a 5-6 membered lactam-containing heterocycloalkyl group, for example, a 6 membered lactam-containing heterocycloalkyl group, and for example, (19)R e In the C6-C 10 Aryl is phenyl or naphthyl, for example phenyl; (20)R c In the case where the halogen is fluorine, chlorine, bromine or iodine, for example iodine; (21)R b-1 wherein the C1-C6 alkane is methyl, ethyl, n-propyl or isopropyl, for example methyl; (22)R b-2 and R b-3 When the nitrogen atom therebetween forms a 3-7 membered heterocyclic ring substituted by one or more C1-C6 alkyl groups, the 3-7 membered heterocyclic ring in the 3-7 membered heterocyclic ring substituted by one or more C1-C6 alkyl groups is a 5-6 membered heterocyclic ring, for example, a 6 membered heterocyclic ring; (23)R b-2 and R b-3 When the nitrogen atom therebetween forms a 3-7 membered heterocyclic ring substituted by one or more C1-C6 alkyl groups, the heteroatom of the 3-7 membered heterocyclic ring substituted by one or more C1-C6 alkyl groups is N, and the number of heteroatoms is 1 to 2, for example, 2; (24)R b-2 and R b-3 When together with the nitrogen atom therebetween, they form a 3-7 membered heterocyclic ring substituted with one or more C1-C6 alkyl groups, the C1-C6 alkyl group is methyl, ethyl, n-propyl or isopropyl, for example methyl; (25)R b-4 In the above, the 5-10 membered heteroaryl group is a 5-6 membered heteroaryl group, for example, a 6 membered heteroaryl group; (26)R b-4 In the 5-10 membered heteroaryl group, the heteroatom of the 5-10 membered heteroaryl group is N, and the number of heteroatoms is 1 to 2, for example, 2; (27)R b-5 wherein the C1-C6 alkyl group is methyl, ethyl, n-propyl or isopropyl, for example, methyl; (28)R b-6 In the above, the C1-C6 alkoxy group is methoxy, ethoxy, n-propoxy or isopropoxy, for example, methoxy; (29)R e-1 wherein the C1-C6 alkyl group substituted by one or more halogens is methyl, ethyl, n-propyl or isopropyl; (30)R e-1 wherein the halogen in the C1-C6 alkyl substituted by one or more halogens is fluorine, chlorine or bromine, for example fluorine; (31)R 3 In the C 1-10 Alkyl is C 1-6 Alkyl, preferably C 1-4 Alkyl, more preferably methyl, ethyl, n-propyl, isopropyl or isobutyl; (32)R 3 In the C 6-14 Aryl is C 6-12 Aryl, preferably phenyl or naphthyl; (33)R 3 wherein the 5-12 membered heterocycloalkyl is a 5-10 membered heterocycloalkyl, preferably a 5-6 membered heterocycloalkyl, and further preferably a piperazinyl, pyrrolidinyl or pyridinyl group; (34)R 3 In the 5-10 membered heteroaryl group, the heteroatom is N, and the number of heteroatoms is 1 to 2. For example, (35)R 3 In the C 5-20 Cycloalkyl C 6-14 Aryl is C 5-16 Cycloalkyl C 6-12 Aryl, preferably C 5-14 Cycloalkylphenyl, more preferably (36) Each R 1-1 wherein the halogen is fluorine, chlorine, bromine or iodine; (37) Each R 1-1 wherein the C2-C6 alkynyl group is an ethynyl group; (38) Each R 1-1 In, C 1-10 Alkyl is C 1-6 Alkyl, preferably C 1-4 Alkyl, more preferably methyl, ethyl, n-propyl, isopropyl or isobutyl; (39) Each R 1-8 wherein the halogen is fluorine, chlorine, bromine or iodine; (40) Each R 1-8 In, C 1-10 Alkyl is C 1-6 Alkyl, preferably C 1-4 Alkyl, more preferably methyl, ethyl, n-propyl, isopropyl or isobutyl; (41) Each R 1-1-2 In, C 1-10 Alkyl is C 1-6 Alkyl, preferably C 1-4 Alkyl, more preferably methyl, ethyl, n-propyl, isopropyl or isobutyl; (42) Each R 1-1-5 In, C 1-10 Alkyl is C 1-6 Alkyl, preferably C 1-4 The alkyl group is more preferably a methyl group, an ethyl group, a n-propyl group, an isopropyl group or an isobutyl group.

4. The use according to claim 2, characterized in that The compound represented by formula C or the compound represented by formula D satisfies one or more of the following conditions: (1)R 1 For H, R 2 C6-C 10 Aryl, one or more R a Substituted C1-C6 alkyl, 5-10 membered heteroaryl, substituted by one or more R f substituted 5-10 membered heteroaryl or one or more R b Substituted C6-C 10 Aryl; or, R 1 and R 2 Together with the nitrogen atom therebetween, a 3-7 membered heterocyclic ring is formed, wherein the heteroatoms in the 3-7 membered heterocyclic ring are selected from one or two of N, O or S, and the number of heteroatoms is 1 to 2; the 5-10 membered heteroaryl group and the one or more R f The heteroatom in the substituted 5-10 membered heteroaryl group is selected from one or two of N, O and S, and the number of the heteroatom is 1 to 2; (2) Each R a are independently benzyl, R a-1 is a C1-C6 alkyl group; (3) Each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocycle, or substituted by one or more R b-5 substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R b-5 The heteroatoms in the substituted 3-7 membered heterocyclic ring are selected from one or two of N, O and S, and the number of heteroatoms is 1 to 4; (4) Each R b-5 are independently hydrogen, or C1-C6 alkyl; (5) Each R f are independently halogen; (6)R 3 C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, 5-10 membered heteroaryl or one or more R 1 -8 substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1-8 The heteroatom in the substituted 5-10 membered heteroaryl group is selected from one or two of N, O and S, and the number of the heteroatom is 1 to 2; (7) Each R 1-1 are independently halogen, nitro, C2-C6 alkynyl, C(O)R 1-1-2 , C 1-6 Alkyl, with one or more R 1-1-13 Substituted C 1-6 Alkyl, or OR 1-1-5 ; (8) Each R 1-8 are independently halogen, C 1-6 Alkyl, with one or more R 1-1-13 Substituted C 1-6 Alkyl, or OR 1-1-5 ; (9) Each R 1-1-2 Independently for C 1-6 alkyl; (10) Each R 1-1-5 Independently for C 1-6 alkyl; (11) Each R 1-1-13 are independently hydroxyl groups; (12)R 1 For H, R 2 C6-C 10 Aryl, benzyl, one or more R a Substituted C1-C6 alkyl, 5-10 membered heteroaryl, substituted by one or more R f substituted 5-10 membered heteroaryl, substituted by one or more R b Substituted C6-C 10 Aryl or one or more R c Substituted benzyl, or, R 1 and R 2 Together with the nitrogen atom therebetween, it forms a 3-7 membered heterocyclic ring or is replaced by one or more R e substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R e The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; the 5-10 membered heteroaryl and the one or more R f The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; preferably, R 2 C6-C 10 Aryl, one or more R a Substituted C1-C6 alkyl, 5-10 membered heteroaryl, substituted by one or more R f substituted 5-10 membered heteroaryl or one or more R b Substituted C6-C 10 Aryl; or, R 1 and R 2 Together with the nitrogen atom therebetween, a 3-7 membered heterocyclic ring is formed; the heteroatoms in the 3-7 membered heterocyclic ring are selected from one or two of N, O or S, and the number of heteroatoms is 1 to 2; the 5-10 membered heteroaryl group and the one or more R f The heteroatom in the substituted 5-10 membered heteroaryl group is selected from one or two of N, O and S, and the number of the heteroatom is 1 to 2; (13) Each R a are independently benzyl, C2-C6 alkynyl or (14)R a-1 is a C1-C6 alkyl group; (15) Each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocycle, or substituted by one or more R b-5 substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R b-5 The heteroatoms in the substituted 3-7 membered heterocyclic ring are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; preferably, each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocycle, or substituted by one or more R b-5 substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R b-5 The heteroatoms in the substituted 3-7 membered heterocyclic ring are selected from one or two of N, O and S, and the number of heteroatoms is 1 to 4; (16) Each R c are independently halogen; (17) Each R f are independently halogen; (18) Each R b-5 are independently hydrogen, or C1-C6 alkyl; (19)R 3 C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, 5-10 membered heteroaryl or one or more R 1-8 substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1-8 The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; preferably, R 3 C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, 5-10 membered heteroaryl or one or more R 1-8 substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1-8 The heteroatom in the substituted 5-10 membered heteroaryl group is selected from one or two of N, O and S, and the number of the heteroatom is 1 to 2; (20) Each R 1-1 are independently halogen, nitro, cyano, C2-C6 alkynyl, C(O)OR 1-1-1 、C(O)R 1-1-2 NR 1-1-3 C(O)R 1-1-4 , C 1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR 1-1-5 Preferably, each R 1-1 are independently halogen, nitro, C2-C6 alkynyl, C(O)R 1-1-2 , C 1-6 Alkyl, with one or more R 1-1-13 Substituted C 1-6 Alkyl, or OR 1-1-5 ; (21) Each R 1-8 are independently halogen, C 1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR 1-1-5 Preferably, each R 1-8 are independently halogen, C 1-6 Alkyl, with one or more R 1-1-13 Substituted C 1-6 Alkyl, or OR 1-1-5 ; (22) Each R 1-1-1 Independently for C 1-10 alkyl; (23) Each R 1-1-2 Independently for C 1-10 Alkyl; preferably, each R 1-1-2 Independently for C 1-6 alkyl; (24) Each R 1-1-3 and R 1-1-4 are independently hydrogen or C 1-10 alkyl; (25) Each R 1-1-5 Independently for C 1-10 Alkyl; preferably, each R 1-1-5 Independently for C 1-6 alkyl; (26) Each R 1-1-13 are independently hydroxyl groups; (27)R b wherein the C1-C6 alkyl group substituted by one or more halogens is trifluoromethyl; (28)R e-1 wherein the C1-C6 group substituted by one or more halogens is a trifluoromethyl group; Preferably, the compound represented by formula C or the compound represented by formula D satisfies one or more of the following conditions: (1)R 1 For H, R 2 C6-C 10 Aryl, benzyl, one or more R a Substituted C1-C6 alkyl, 5-10 membered heteroaryl, substituted by one or more R f substituted 5-10 membered heteroaryl, substituted by one or more R b Substituted C6-C 10 Aryl or one or more R c substituted benzyl; or, R 1 and R 2 Together with the nitrogen atom therebetween, it forms a 3-7 membered heterocyclic ring or is replaced by one or more R e substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R e The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; the 5-10 membered heteroaryl and the one or more R f The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of the heteroatoms is 1 to 4; Each R a are independently benzyl, C2-C6 alkynyl or R a-1 is a C1-C6 alkyl group; Each R b are independently C2-C6 alkynyl, halogen, hydroxyl, carboxyl, C1-C6 alkyl substituted by one or more halogens, C1-C6 alkyl substituted by one or more hydroxyl groups, 3-7 membered heterocycle, or substituted by one or more R b-5 substituted 3-7 membered heterocyclic ring; when there are multiple substituents, the substituents are the same or different; the 3-7 membered heterocyclic ring and one or more R b-5 The heteroatom in the substituted 3-7 membered heterocyclic ring is selected from one or more of N, O and S, and the number of the heteroatom is 1 to 4; Each R c are independently halogen; Each R e Independently C6-C 10 Aryl or one or more R e-1 Substituted C6-C 10 Aryl; when there are multiple substituents, the substituents are the same or different; Each R f are independently halogen; Each R b-5 are independently hydrogen, or C1-C6 alkyl; Each R e-1 is independently a C1-C6 alkyl group substituted by one or more halogens; when there are multiple substituents, the substituents are the same or different; (2)R 3 C 6-14 Aryl, one or more R 1-1 Substituted C 6-14 Aryl, 5-10 membered heteroaryl or one or more R 1 -8 substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl and one or more R 1-8 The heteroatoms in the substituted 5-10 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 to 4; Each R 1-1 are independently halogen, nitro, cyano, C2-C6 alkynyl, C(O)OR 1-1-1 、C(O)R 1-1-2 NR 1-1-3 C(O)R 1-1-4 , C 1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR 1-1-5 ; Each R 1-8 are independently halogen, C 1-10 Alkyl, with one or more R 1-1-13 Substituted C 1-10 Alkyl, or OR 1-1-5 ; Each R 1-1-1 Independently for C 1-10 alkyl; Each R 1-1-2 Independently for C 1-10 alkyl; Each R 1-1-3 and R 1-1-4 are independently hydrogen or C 1-10 alkyl; Each R 1-1-5 Independently for C 1-10 alkyl; Each R 1-1-13 are independently hydroxyl groups; More preferably, the compound represented by formula C or the compound represented by formula D satisfies one or more of the following conditions: (1)R 1 is hydrogen; R 2 for or, for Preferably R 2 for , for (2)R 3 for Preferably 5. The use according to claim 2, characterized in that The compound shown in formula C is any of the following compounds: And / or, the compound as shown in formula D is any of the following compounds:

6. The use according to claim 2, characterized in that: The application meets one or more of the following conditions: (1) The solvent is an organic solvent, water, or a mixed solvent of an organic solvent and water; preferably a mixed solvent of an organic solvent and water, more preferably a volume ratio of the organic solvent to water of 1:1; (2) When the solvent comprises an organic solvent, the organic solvent is one or more of acetonitrile, methanol, DMF, dimethyl sulfoxide, sulfolane, dichloromethane and ethyl acetate, for example, one or more of acetonitrile, methanol and DMF; preferably, the solvent is an acetonitrile / water solvent system, methanol or DMF; (3) The molar ratio of the amine compound or alcohol-phenol compound to the fluorosulfonylguanidine compound of Formula 1 is 1:(0.3-2), for example, 1:0.33, 1:0.5, 1:0.6, 1:0.83, 1:1 or 1:2; (4) The molar volume ratio of the amine compound or alcohol-phenol compound to the solvent is 0.13 mol / L to 1.5 mol / L, for example: 0.13 mol / L, 0.2 mol / L, 0.25 mol / L, 0.33 mol / L, 0.4 mol / L, 0.5 mol / L, 0.6 mol / L, 0.63 mol / L, 1.0 mol / L or 1.5 mol / L; (5) The reaction further comprises a base, which is one or more of an alkali metal carbonate, an alkali metal phosphate, an alkali metal hydroxide, an alkali metal bicarbonate and an organic base, such as N,N-diisopropylethylamine and / or triethylenediamine; (6) When the reaction further comprises a base, the molar ratio of the amine compound to the base is 1:(2-3), for example 1:2, 1:2.2 or 1:3; (7) The reaction only includes the amine compound and / or the phenolic alcohol compound, the fluorosulfonylguanidine compound as described in Formula 1, and the solvent; or, the reaction only includes the amine compound and / or the phenolic alcohol compound, the fluorosulfonylguanidine compound as described in Formula 1, the solvent, and a base; (8) The reaction temperature is 0-100°C, for example 60-80°C, preferably 70°C; (9) The reaction time is 5 min-24 h, for example 10 min-24 h, further for example: 2 h, 4 h, 16 h, 20 h or 24 h; (10) The post-treatment of the reaction may include the following steps: quenching, washing and removing the solvent; preferably, the quenching process may use water or an acid aqueous solution, preferably an aqueous solution; the acid in the acid aqueous solution is an organic acid, such as citric acid; preferably, when the acid aqueous solution is used for quenching, preferably, the acid aqueous solution is added to make the pH value 4; preferably, the washing process may use water or saturated saline for washing; preferably, the quenching and washing processes may further include extraction, and the type of organic solvent used in the extraction is conventional in the art, such as ethyl acetate; preferably, the extraction is performed 3 or 4 times; preferably, the process of removing the solvent may use a reduced pressure concentration method; (11) The post-treatment step of the reaction may further include purification, wherein the purification is column chromatography.

7. A fluorosulfonylguanidine as shown in Formula 1, 8. A method for preparing fluorosulfonylguanidine as shown in formula 1, characterized in that: It includes the following steps: In the presence of a base, compound 2 reacts with sulfuryl fluoride in a solvent to obtain a fluorosulfonylguanidine as shown in Formula 1; 9. The method for preparing the compound of formula 1 according to claim 8, characterized in that: It meets one or more of the following conditions: (1) The solvent is one or more of a hydrocarbon solvent, a halogenated hydrocarbon solvent, a nitrogen-containing compound solvent, an ether solvent, an ester solvent, a ketone solvent and a sulfur-containing compound solvent, for example, a nitrogen-containing compound solvent; wherein the hydrocarbon solvent is benzene and / or toluene; the halogenated hydrocarbon solvent is one or more of dichloromethane, 1,2-dichloroethane and chloroform; the nitrogen-containing compound solvent is one or more of acetonitrile, N,N-dimethylformamide (DMF) and N-methylpyrrolidone, for example, N,N-dimethylformamide (DMF); the ether solvent is one or more of 1,4-dioxane, diethyl ether, methyl tert-butyl ether (MTBE) and tetrahydrofuran; the ester solvent is ethyl acetate; the ketone solvent is acetone; and the sulfur-containing compound solvent is dimethyl sulfoxide (DMSO); (2) The base is one or more of alkali metal carbonates, alkali metal phosphates, alkali metal hydroxides, alkali metal bicarbonates and organic bases, for example, organic bases; wherein the alkali metal carbonate is one or more of potassium carbonate, cesium carbonate and sodium carbonate, preferably cesium carbonate and / or potassium carbonate, more preferably potassium carbonate; the alkali metal phosphate is tripotassium phosphate; the alkali metal hydroxide is sodium hydroxide and / or potassium hydroxide; the alkali metal bicarbonate is sodium bicarbonate and / or potassium bicarbonate; the organic base is triethylamine and / or N,N-diisopropylethylamine; (3) In the method for preparing fluorosulfonylguanidine as shown in Formula 1, the sulfuryl fluoride is introduced by evacuating the reaction system to negative pressure and then introducing the sulfuryl fluoride gas at once; (4) In the method for preparing the fluorosulfonyl group as shown in Formula 1, the molar ratio of the compound 2 to the sulfuryl fluoride is (1.2-2):1, for example, 1.5:1; (5) In the method for preparing the fluorosulfonylguanidine as shown in Formula 1, the molar volume ratio of the compound 2 to the solvent is 0.5 mol / L to 3 mol / L, for example 2.26 mol / L; (6) In the method for preparing the fluorosulfonyl group as shown in Formula 1, the molar ratio of the compound 2 to the base is 1:(2-7), for example 1:3; (7) In the method for preparing the fluorosulfonyl group as shown in Formula 1, the reaction temperature is -20°C to 60°C, for example, 50°C; (8) In the method for preparing the fluorosulfonylguanidine as shown in Formula 1, the progress of the reaction can be monitored by TLC or HPLC, and the end point of the reaction is generally when the sulfuryl fluoride gas is completely consumed; the reaction time is 0.5-48 hours, for example 5 hours; (9) In the preparation method of the fluorosulfonylguanidine as shown in Formula 1, the preparation method may further include post-treatment, and the post-treatment includes the following steps: quenching and extraction; the quenching is quenching with water; the solvent of the extraction is water and an organic solvent, and the type of the organic solvent is methyl tert-butyl ether and / or ethyl acetate; (10) Compound 2 is in the form of a guanidine salt; the guanidine salt is, for example, one or more of guanidine hydrochloride, guanidine sulfate, guanidine nitrate and guanidine carbonate, and is also, for example, guanidine hydrochloride; (11) The compound 2 is directly subjected to the preparation reaction of the fluorosulfonylguanidine shown in Formula 1 as described above without isolation.

10. An aminosulfonylguanidine as shown in formula C or an N-amidinosulfamate as shown in formula D, R 1 and R 2 The definition as in any one of claims 2 to 6; R 3 The definition of any one of claims 2 to 6.

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