CN116836100A - 2-aminopyrrole compound and preparation method and application thereof - Google Patents

2-aminopyrrole compound and preparation method and application thereof Download PDF

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CN116836100A
CN116836100A CN202210301956.XA CN202210301956A CN116836100A CN 116836100 A CN116836100 A CN 116836100A CN 202210301956 A CN202210301956 A CN 202210301956A CN 116836100 A CN116836100 A CN 116836100A
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alkyl
aryl
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鲍红丽
栗泰安
叶长青
李亚军
朱能波
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Fujian Institute of Research on the Structure of Matter of CAS
Mindu Innovation Laboratory
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Fujian Institute of Research on the Structure of Matter of CAS
Mindu Innovation Laboratory
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
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    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
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Abstract

The application discloses a 2-aminopyrrole compound, a preparation method and application thereof. 2-aminopyrrole compounds, wherein the 2-aminopyrrole compounds have a structure shown in a formula I:wherein R is 1 And R is 2 Independently selected from C 1 ～C 13 Alkyl, ester, carboxylic acid, amide, substituted amino, C 1 ～C 13 Alkoxy, C 6 ～C 20 Aryl, C 2 ～C 20 Heteroaryl, substituted C 1 ～C 13 Alkyl, substituted C 6 ～C 20 Aryl, substituted C 2 ～C 20 Heteroaryl groups. The 2-aminopyrrole compound has various structures, has two aryl groups which can be highly functionalized, and is convenient for subsequent coupling and assembly; the pyrrolopyrimidine compound has various structures and solid fluorescence properties; the preparation method has the advantages of easily available raw materials, simple method, convenient operation and higher yield.

Description

2-aminopyrrole compound and preparation method and application thereof
Technical Field
The application relates to a 2-aminopyrrole compound, a preparation method and application thereof, belonging to the field of organic synthesis.
Background
Pyrrole compounds exist widely in animals and plants, and are widely applied to the fields of medicines, natural products and materials. Conjugated aromatic molecules with push-pull electronic structures often have luminescent properties and have wide application in the field of luminescent materials, so that the synthesis method of pyrrole compounds and application research thereof are concerned by organic synthesis chemists. The current routes for preparing pyrrole are relatively rich: 1. by classical organic name reaction Hantzsch pyrrole synthesis method, paal-Knorr pyrrole synthesis method, knorr pyrrole synthesis method and the like; 2. the pyrrole compound is constructed by cyclizing a starting compound having a specific structure, such as 1, 3-eneyne, 1, 4-alkynylamine, heterocycle, etc., under a certain condition. The former method is mature and is widely applied, but the obtained product pyrrole is of a specific structure. The latter has higher purpose, needs to carry out pre-designed synthesis on the substrate, and the latter has higher efficiency and builds a certain pyrrole molecular structure more directly.
The 2-aminopyrrole compound is a compound with an amino cyano group intramolecular push-pull electronic structure, and amino and cyano groups can perform various reactions.
Disclosure of Invention
According to one aspect of the present application, there is provided a 2-aminopyrrole compound.
The compound has two aryl groups which can be connected with various substituents, and is convenient for subsequent coupling and assembly.
A 2-aminopyrrole compound, its polymorphs, solvates or salts thereof, the 2-aminopyrrole compound having the structure of formula i:
wherein R is 1 And R is 2 Independently selected from C 1 ～C 13 Alkyl, ester, carboxylic acid, amide, substituted amino, C 1 ～C 13 Alkoxy, C 6 ～C 20 Aryl, C 2 ～C 20 Heteroaryl, substituted C 1 ～C 13 Alkyl, substituted C 6 ～C 20 Aryl, substituted C 2 ～C 20 Heteroaryl;
preferably, R 1 And R is 2 Independently selected from C 1 ～C 7 Alkyl, ester, carboxylic acid, amide, substituted amino, C 1 ～C 7 Alkoxy, C 6 ～C 10 Aryl, C 2 ～C 10 Heteroaryl, substituted C 1 ～C 7 Alkyl, substituted C 6 ～C 10 Aryl, substituted C 2 ～C 10 Heteroaryl groups.
Optionally substituted C 1 ～C 13 The substituent of the alkyl group being R a ；
The R is a Selected from deuterium atoms, halogens, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 13 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 13 Oxo aryl, boric acid and silane、C 1 ～C 13 Alkyl phosphine, C 6 ～C 13 Aryl phosphine, -CN, -NO 2 At least one of them.
Optionally substituted C 6 ～C 20 The substituent of the aryl group is R b ；
The R is b Selected from deuterium atoms, halogens, C 1 ～C 13 Alkyl, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 20 Heteroaryl, C 2 ～C 20 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 20 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 20 Aryl phosphine, thioalkyl, sulfonyl, -CN, -NO 2 At least one of them.
Optionally substituted C 2 ～C 20 Heteroaryl has R as substituent c ；
The R is c Independently selected from deuterium atoms, halogens, C 1 ～C 13 Alkyl, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 20 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 20 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 20 Aryl phosphine, -CN, -NO 2 At least one of them.
Alternatively, the structural formula of the compound represented by formula I is selected from the following compounds:
according to a further aspect of the present application, there is provided a process for the preparation of 2-aminopyrroles. The preparation method is a method for preparing 2-aminopyrrole from alpha-beta unsaturated imine. The method is simple, the pyrrole is synthesized from imine in one step, and the yield is high. The product treatment method directly adds water to separate out and filter, and column chromatography is not needed.
A preparation method of 2-aminopyrrole compounds comprises the following steps:
(S) reacting a mixture containing an alpha-beta unsaturated imine compound, a base, an organic solvent and trimethylnitrile silane under an inert gas to obtain a 2-aminopyrrole compound
Or (b)
(A) The mixture containing alpha-beta unsaturated cyano sulfonamide, alkali, organic solvent and trimethylnitrile silane is reacted under the condition of inactive gas to obtain the 2-aminopyrrole compound
The structural formula of the alpha-beta unsaturated imine compound is as follows:
the alpha-beta unsaturated cyano sulfonamide has the structural formula:
wherein R is 1 And R is R 1 The same; r is R 2 And R is R 2 The same;
R 3 independently selected from C 1 ～C 13 Alkyl, C 3 ～C 8 Cycloalkyl, C 6 ～C 20 Aryl, -NO 2 、-CF 3 、-OH、-NH 2 ；
Alternatively, C 1 ～C 13 The alkyl groups being unsubstituted or substituted by one or more R' s A Substituted by substituent groups, said R A Selected from halogen, cycloalkyl, aryl, -OH, -NH 2 、-CN、-NO 2 、-CF、-CO 2 H；
C 3 ～C 8 Aryl is unsubstituted or substituted by one or even more R B Substituted by substituent groups, said R B Selected from halogen, alkyl, cycloalkyl, -OH, -NH 2 、-CN、-NO 2 、-CF、-CO 2 H。
The 2-aminopyrrole compound is selected from the 2-aminopyrrole compounds described in any one of the above.
Alternatively, the α - β unsaturated cyano sulfonamide is obtained from the addition of an α - β unsaturated imine compound and a 1,2 cyano group.
Optionally, in the step (S), the base is at least one selected from potassium carbonate, sodium tert-butoxide, potassium fluoride, triethylamine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 4-dimethylaminopyridine and triethylenediamine.
Optionally, the organic solvent is at least one selected from acetonitrile, N-dimethylformamide, tetrahydrofuran, N-methylpyrrolidone, and 1, 4-dioxane.
Optionally, the inactive gas is selected from one of nitrogen, argon and helium.
Optionally, the mass to volume ratio of the alpha-beta unsaturated imine compound to the organic solvent is 10 mg/mL-100 mg/mL.
Alternatively, the mass ratio of the α - β unsaturated imine compound to the base substance is 1:0.5 to 1:5, a step of;
preferably, the mass ratio of the α - β unsaturated imine compound to the base substance is 1:1.5 to 1:2.5.
alternatively, the mass ratio of the α - β unsaturated imine compound to the trimethylnitrile silane is 1:0.1 to 1:5, a step of;
preferably, the mass ratio of the α - β unsaturated imine compound to the trimethylnitrile silane is 1: 2-1: 2.2.
alternatively, the reaction conditions are as follows:
the temperature is 0-100 ℃;
the time is 0.5 to 24 hours.
Optionally, in the step (a), the base is at least one selected from potassium carbonate, sodium tert-butoxide, potassium fluoride, triethylamine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 4-dimethylaminopyridine and triethylenediamine.
Optionally, the organic solvent is at least one selected from acetonitrile, N-dimethylformamide, tetrahydrofuran, N-methylpyrrolidone, and 1, 4-dioxane.
Optionally, the inactive gas is selected from one of nitrogen, argon and helium.
Optionally, the mass to volume ratio of the alpha-beta unsaturated cyano sulfonamide to the organic solvent is 11 mg/mL-110 mg/mL.
Alternatively, the mass ratio of the α - β unsaturated cyano sulfonamide to the base material is 1:0.5 to 1:5, a step of;
preferably, the mass ratio of the α - β unsaturated cyano sulfonamide to the base material is 1:1.5 to 1:2.5.
alternatively, the mass ratio of the α - β unsaturated cyano sulfonamide to the trimethylnitrile silane is 1:0.1 to 1:5, a step of;
preferably, the mass ratio of the α - β unsaturated cyano sulfonamide to the trimethylnitrile silane is 1:0.5 to 1:1.3.
alternatively, the reaction conditions are as follows:
the temperature is 0-100 ℃;
the time is 0.5 to 24 hours.
According to a third aspect of the present application there is provided a pyrrolopyrimidine compound.
The pyrrolopyrimidine compound prepared from the 2-aminopyrrole compound and/or the 2-aminopyrrole compound obtained by the preparation method has a structure shown in a formula II:
R 4 、R 5 、R 6 independently selected from C 1 ～C 13 Alkyl, C 6 ～C 20 Aryl, C 2 ～C 20 Heteroaryl, substituted C 1 ～C 13 Alkyl, substituted C 6 ～C 20 Aryl, substituted C 2 ～C 20 Heteroaryl;
preferably, R 4 、R 5 、R 6 Independently selected from C 1 ～C 7 Alkyl, C 6 ～C 10 Aryl, C 2 ～C 10 Heteroaryl, substituted C 1 ～C 7 Alkyl, substituted C 6 ～C 10 Aryl, substituted C 2 ～C 10 Heteroaryl groups.
Optionally substituted C 1 ～C 13 The substituent of the alkyl group being R d ；
The R is d Independently selected from deuterium atoms, halogens, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 13 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 13 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 13 Aryl phosphine, -CN, -NO 2 At least one of them.
Optionally substituted C 6 ～C 20 The substituent of the aryl group is R e ；
The R is e Selected from deuterium atoms, halogens, C 1 ～C 13 Alkyl, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 20 Heteroaryl, C 2 ～C 20 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 20 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 20 Aryl phosphine, thioalkyl, sulfonyl, -CN, -NO 2 At least one of them.
Optionally substituted C 2 ～C 20 Heteroaryl has R as substituent f ；
The R is f Independently selected from deuterium atoms, halogens, C 1 ～C 13 Alkyl, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 20 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 20 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 20 Aryl phosphine, -CN, -NO 2 At least one of them.
Alternatively, the structural formula of the compound represented by formula II is selected from the following compounds:
optionally, the pyrrolopyrimidine compound is prepared from the 2-aminopyrrole compound and/or the 2-aminopyrrole compound obtained by the preparation method.
According to a fourth aspect of the present application, there is provided a process for the preparation of pyrrolopyrimidines.
A preparation method of a pyrrolopyrimidine compound comprises the following steps:
the mixture containing 2-aminopyrrole compounds, diketones and solvent reacts under the condition of inactive gas to obtain pyrrolopyrimidine compounds
Optionally, the diketone is selected from one of 2, 6-dimethyl-3, 5-heptanedione and acetylacetone.
Alternatively, the solvent is selected from one of glacial acetic acid, a mixture of glacial acetic acid and water.
Optionally, the volume ratio of the glacial acetic acid to the water mixture is 1:1.
Optionally, the inert gas is selected from one of nitrogen, argon and helium.
Optionally, the mass ratio of the 2-aminopyrrole compound to the diketone is 1:1-1:10.
Alternatively, the reaction conditions are as follows:
the temperature is 15-125 ℃;
the time is 0.5 to 48 hours.
According to a fifth aspect of the present application there is provided the use of a 2-aminopyrrole compound.
The application of the 2-aminopyrrole compound and/or the 2-aminopyrrole compound obtained by the preparation method in preparing pyrrolopyrimidine compounds.
According to a sixth aspect of the present application there is provided the use of a pyrrolopyrimidine compound.
The pyrrolopyrimidine compounds and/or the pyrrolopyrimidine compounds obtained by the preparation method are used as fluorescent molecules or applied to medicines.
In the application, C 1 ～C 13 、C 6 ～C 20 And the like refer to the number of carbon atoms contained in the group.
In the present application, the term "alkyl" refers to a group formed by the loss of any one hydrogen atom from an alkane compound molecule.
In the present application, the term "alkenyl" refers to a group formed by the loss of any one hydrogen atom from an olefin compound molecule.
In the present application, the term "alkynyl" refers to a group formed by the loss of any one hydrogen atom from an alkyne compound molecule.
In the present application, the term "aryl" refers to a group formed by the removal of one hydrogen atom on an aromatic ring from an aromatic compound molecule; for example, toluene loses p-tolyl group formed by the hydrogen atom at the para-position of the methyl group on the benzene ring.
In the present application, the term "halogen" means at least one of fluorine, chlorine, bromine, iodine.
In the present application, the term "heterocyclic group" means a group formed by losing any one of hydrogen atoms from an organic compound having a heterocyclic structure in a molecule, and atoms constituting a ring contain at least one hetero atom including nitrogen atom, sulfur atom and oxygen atom in addition to carbon atom.
In the present application, the term "polyfluoroalkyl" refers to a group formed by substitution of any number of hydrogen atoms on an alkyl compound molecule with fluorine atoms.
In the present application, the term "substituted amino" refers to a group formed by substitution of any one of the hydrogen atoms on the amino compound molecule.
In the present application, the term "substituted alkyl" refers to a group formed by substitution of any one of the hydrogen atoms on the alkyl compound molecule.
In the present application, the term "substituted aryl" refers to a group formed by substitution of any one of the hydrogen atoms on the aryl compound molecule.
In the present application, the term "substituted heteroaryl" refers to a group formed by substitution of any one of the hydrogen atoms on the heteroaryl compound molecule.
In the present application, the term "cycloalkyl" refers to a group formed by the loss of any one hydrogen atom from a naphthenic compound molecule.
In the present application, the term "oxo alkyl" refers to a group formed by oxo substitution of any one of the hydrogen atoms on an alkane compound molecule.
In the present application, the terms "ester group", "carboxylic acid group", "amide group" refer to the structural formula as follows:
wherein "M" is "O" when it is "ester group"; "Carboxylic" when "M" is "OH"; and "amide" when "M" is "NH".
The compounds described above and their NMR data are shown in the following table:
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the application has the beneficial effects that:
1) The 2-aminopyrrole compound provided by the application has various structures, has two aryl groups which can be highly functionalized, and is convenient for subsequent coupling and assembly.
2) The pyrrolopyrimidine compound provided by the application has various structures and solid fluorescence properties, and is a very useful fluorescent molecule.
3) The preparation method provided by the application has the advantages of easily available raw materials and simple method; the pyrrole is synthesized from the imine in one step, and the method has the advantage of high yield; the product treatment method can directly add water for precipitation and filtration without column chromatography, thereby leading the operation to be simpler and more convenient.
Detailed Description
The present application is described in detail below with reference to examples, but the present application is not limited to these examples.
Unless otherwise indicated, all starting materials in the examples of the present application were purchased commercially.
The analysis method in the embodiment of the application is as follows:
nuclear magnetic resonance analysis was performed using Bruker-Biospin AVANCE III HD and JEOL ECZ 600R.
The yields in the examples of the present application were calculated as follows:
in the examples of the present application, the yield of 2-aminopyrroles = mass of actual product/mass of theoretical product x 100%;
yield of pyrrolopyrimidines = mass of actual product/mass of theoretical product x 100%.
Synthesis of 2-aminopyrroles
Example 1
180mg of bisphenol alpha-beta unsaturated p-toluenesulfonimide and 138mg of potassium carbonate are added into a reaction tube, and nitrogen is introduced. Then 4ml acetonitrile was added as solvent and 55. Mu.l TMSCN (trimethylnitrile silane) was added. After 12 hours of reaction at 70 ℃, the reaction mixture was dried by spin-drying and passed through a column to give compound 1 (56 mg, yield 43%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(600MHz,DMSO-d 6 )δ11.40(s,1H),7.68(d,J＝7.5Hz,2H),7.49–7.41(m,4H),7.37(t,J＝7.7Hz,2H),7.27(t,J＝7.4Hz,1H),7.18(t,J＝7.3Hz,1H),4.84(s,2H).
example 2
160mg of 4-chlorobenzene-phenyl alpha-beta unsaturated methylsulfonylimide and 106mg of sodium carbonate were added to the reaction tube, and nitrogen gas was introduced. Then 4ml of N, N-Dimethylformamide (DMF) was added as solvent and 55. Mu.l TMSCN was added. After reaction at 20℃for 1 hour, the reaction mixture was dried by spin-drying, and the resultant was passed through a column to obtain Compound 6 (25 mg, yield 17%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ11.46(s,1H),7.71(d,J＝7.7Hz,2H),7.59–7.39(m,6H),7.32(t,J＝7.3Hz,1H),4.97(s,2H).
example 3
161mg of thiophene-phenyl alpha-beta unsaturated nitro-sulfonyl imide and 80mg of sodium tert-butoxide are added into a reaction tube, and nitrogen is introduced. Then, 4ml of Tetrahydrofuran (THF) was added as a solvent, and 55. Mu.l of TMSCN was added. After reacting at 60℃for 2 hours, the reaction mixture was dried by spin-drying, and the resultant was passed through a column to obtain compound 17 (21 mg, yield 16%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ11.5(s,1H),7.7(d,J＝7.0Hz,2H),7.5–7.4(m,3H),7.4–7.3(m,1H),7.2(s,1H),7.1(s,1H),5.0(s,2H).
example 4
218mg of pyrene-phenyl alpha-beta unsaturated cyclopropylsulfonyl imide and 58mg of potassium fluoride (KF) were added to a reaction tube, and nitrogen gas was introduced. 4ml of toluene was then added as solvent, and 55. Mu.l TMSCN was added. After 4 hours of reaction at 50℃the reaction mixture was dried by spin-drying and passed through a column to give compound 16 (71 mg, yield 37%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ11.64(s,1H),8.35(d,J＝7.9Hz,1H),8.33–8.28(m,2H),8.24–8.18(m,3H),8.14–8.07(m,2H),8.05(d,J＝7.9Hz,1H),7.82(d,J＝7.5Hz,2H),7.51(t,J＝7.8Hz,2H),7.34(t,J＝7.4Hz,1H),4.73(s,2H).
example 5
204mg of 4-trifluoromethyl-phenyl alpha-beta unsaturated trifluoromethylsulfanimine and 101mg of Triethylamine (TEA) were added to a reaction tube, and nitrogen gas was introduced thereinto. Then 4ml of N-methylpyrrolidone (NMP) was added as solvent and 55. Mu.l TMSCN was added. After reaction at 90℃for 8 hours, the reaction mixture was dried by spin-drying and passed through a column to give compound 7 (47 mg, yield 29%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ11.53(s,1H),7.79–7.67(m,6H),7.49(t,J＝7.8Hz,2H),7.34(t,J＝7.4Hz,1H),5.16(s,2H).
example 6
242mg of bis 4-methylthiophenyl alpha-beta-p-nitrobenzenesulfonimide and 152mg of 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) were charged into a reaction tube, and nitrogen gas was introduced. Then 4ml of 1, 4-dioxane was added as solvent and 55. Mu.l TMSCN was added. After 10 hours of reaction at 100℃the reaction mixture was dried by spin-drying and passed through a column to give compound 31 (49 mg, yield 28%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ11.37(s,1H),7.65(d,J＝8.4Hz,2H),7.43(d,J＝8.3Hz,2H),7.39–7.26(m,4H),4.85(s,2H),2.50(s,6H).
example 7
212mg of phenyl-biphenyl alpha-beta unsaturated pyridine sulfonyl imide and 122mg of 4-dimethylaminopyridine are added into a reaction tube, and nitrogen is introduced. Then 4ml DMF was added as solvent and 55. Mu.l TMSCN was added. After 24 hours of reaction at 80 ℃, the reaction mixture was dried by spin-drying and passed through a column to give compound 20 (72 mg, yield 43%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ11.54(s,1H),7.87–7.79(m,4H),7.74(d,J＝7.3Hz,2H),7.54–7.47(m,4H),7.43(t,J＝7.7Hz,2H),7.38(t,J＝7.3Hz,1H),7.23(t,J＝7.3Hz,1H),4.94(s,2H).
example 8
Phenyl-4-methylsulfonylphenyl alpha-beta unsaturated hydroxysulfonimide 183mg and triethylenediamine 122mg were added to a reaction tube, and nitrogen gas was introduced. Then 4ml of DMSO was added as solvent and 55. Mu.l TMSCN was added. After 5 hours of reaction at 75 ℃, the reaction mixture was dried by spin-drying and passed through a column to give compound 27 (74 mg, yield 44%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(400MHz,DMSO-d 6 )δ11.67(s,1H),8.00–7.82(m,4H),7.52–7.35(m,4H),7.26–7.13(m,1H),5.06(s,2H),3.19(s,3H).
synthesis of pyrrolopyrimidines
Example 9
130mg of diphenyl 2-aminopyrrole and 156mg of 2, 6-dimethyl-3, 5-heptanedione were added to a reaction tube, and nitrogen gas was introduced thereinto. Then 2ml of glacial acetic acid was added as solvent. After 6 hours of reaction, the organic phase was extracted and passed through a column to give compound 37 (84 mg, yield 45%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(400MHz,Chloroform-d)δ8.14(d,J＝7.6Hz,2H),7.53–7.41(m,7H),7.30(t,J＝7.4Hz,1H),6.50(s,1H),3.12–2.93(m,2H),1.33(d,J＝6.9Hz,6H),1.01(d,J＝6.7Hz,6H).
example 10
175mg of bis-p-methylthiophenyl 2-aminopyrrole and 500mg of acetylacetone were added to the reaction tube, and nitrogen gas was introduced. Then 10ml of glacial acetic acid and water (volume ratio of glacial acetic acid to water 1:1) were added as solvents. After 24 hours of reaction, the organic phase was extracted and passed through a column to give compound 41 (109 mg, yield 53%).
The nuclear magnetic detection data of the product are as follows:
1 H NMR(400MHz,Chloroform-d)δ7.98(d,J＝8.3Hz,2H),7.43–7.35(m,4H),7.31(d,J＝8.2Hz,2H),6.33(s,1H),2.55(s,3H),2.52(s,3H),2.50(s,3H),2.11(s,3H).
while the application has been described in terms of preferred embodiments, it will be understood by those skilled in the art that various changes and modifications can be made without departing from the scope of the application, and it is intended that the application is not limited to the specific embodiments disclosed.

Claims (10)

1. A 2-aminopyrrole compound, its polymorphs, solvates or salts thereof, characterized in that the 2-aminopyrrole compound has the structure of formula i:
wherein R is 1 And R is 2 Independently selected from C 1 ～C 13 Alkyl, ester, carboxylic acid, amide, substituted amino, C 1 ～C 13 Alkoxy, C 6 ～C 20 Aryl, C 2 ～C 20 Heteroaryl, substituted C 1 ～C 13 Alkyl, substituted C 6 ～C 20 Aryl, substituted C 2 ～C 20 Heteroaryl groups.
2. The 2-aminopyrroles according to claim 1 wherein R is 1 And R is 2 Independently selected from C 1 ～C 7 Alkyl, ester, carboxylic acid, amide, substituted amino, C 1 ～C 7 Alkoxy, C 6 ～C 10 Aryl, C 2 ～C 10 Heteroaryl, substituted C 1 ～C 7 Alkyl, substituted C 6 ～C 10 Aryl, substituted C 2 ～C 10 Heteroaryl;
preferably, substituted C 1 ～C 13 The substituent of the alkyl group being R a ；
The R is a Selected from deuterium atoms, halogens, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl group、C 3 ～C 6 Cycloalkyl, C 2 ～C 13 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 13 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 13 Aryl phosphine, -CN, -NO 2 At least one of (a) and (b);
preferably, substituted C 6 ～C 20 The substituent of the aryl group is R b ；
The R is b Selected from deuterium atoms, halogens, C 1 ～C 13 Alkyl, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 20 Heteroaryl, C 2 ～C 20 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 20 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 20 Aryl phosphine, thioalkyl, sulfonyl, -CN, -NO 2 At least one of (a) and (b);
preferably, substituted C 2 ～C 20 Heteroaryl has R as substituent c ；
The R is c Independently selected from deuterium atoms, halogens, C 1 ～C 13 Alkyl, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 20 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 20 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 20 Aryl phosphine, -CN, -NO 2 At least one of them.
3. 2-aminopyrroles according to claim 1 wherein the structural formula of the compound of formula i is selected from the group consisting of:
4. the preparation method of the 2-aminopyrrole compound is characterized by comprising the following steps of:
(S) reacting a mixture containing an alpha-beta unsaturated imine compound, alkali, an organic solvent and trimethylnitrile silane under an inactive gas to obtain a 2-aminopyrrole compound;
or (b)
(A) Reacting a mixture containing alpha-beta unsaturated cyano sulfonamide, alkali, an organic solvent and trimethylnitrile silane under an inactive gas to obtain a 2-aminopyrrole compound;
the structural formula of the alpha-beta unsaturated imine compound is as follows:
the alpha-beta unsaturated cyano sulfonamide has the structural formula:
wherein R is 1 And R is R 1 The same; r is R 2 And R is R 2 The same;
R 3 independently selected from C 1 ～C 13 Alkyl, C 3 ～C 8 Cycloalkyl, C 6 ～C 20 Aryl, -NO 2 、-CF 3 、-OH、-NH 2 ；
Preferably C 1 ～C 13 The alkyl groups being unsubstituted or substituted by one or more R' s A Substituted by substituent groups, said R A Selected from halogen, cycloalkyl, aryl, -OH, -NH 2 、-CN、-NO 2 、-CF、-CO 2 H；
C 3 ～C 8 Aryl is unsubstituted or substituted by one or even more R B Substituted by substituentsThe R is B Selected from halogen, alkyl, cycloalkyl, -OH, -NH 2 、-CN、-NO 2 、-CF、-CO 2 H。
The 2-aminopyrrole compound is selected from the 2-aminopyrrole compounds according to any one of claims 1 to 3.
5. The process according to claim 4, wherein in the step (S), the base is at least one selected from the group consisting of potassium carbonate, sodium t-butoxide, potassium fluoride, triethylamine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 4-dimethylaminopyridine and triethylenediamine;
preferably, the organic solvent is at least one selected from acetonitrile, N-dimethylformamide, tetrahydrofuran, N-methylpyrrolidone and 1, 4-dioxane;
preferably, the inactive gas is selected from one of nitrogen, argon and helium;
preferably, the mass to volume ratio of the alpha-beta unsaturated imine compound to the organic solvent is 10 mg/mL-100 mg/mL;
preferably, the mass ratio of the α - β unsaturated imine compound to the base substance is 1:0.5 to 1:5, a step of;
preferably, the mass ratio of the α - β unsaturated imine compound to the base substance is 1:1.5 to 1:2.5;
preferably, the mass ratio of the α - β unsaturated imine compound to the trimethylnitrile silane is 1:0.1 to 1:5, a step of;
preferably, the mass ratio of the α - β unsaturated imine compound to the trimethylnitrile silane is 1: 2-1: 2.2;
preferably, the reaction conditions are as follows:
the temperature is 0-100 ℃;
the time is 0.5 to 24 hours.
6. The process according to claim 4, wherein in the step (A), the base is at least one selected from the group consisting of potassium carbonate, sodium t-butoxide, potassium fluoride, triethylamine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 4-dimethylaminopyridine and triethylenediamine;
preferably, the organic solvent is at least one selected from acetonitrile, N-dimethylformamide, tetrahydrofuran, N-methylpyrrolidone and 1, 4-dioxane;
preferably, the inactive gas is selected from one of nitrogen, argon and helium;
preferably, the mass to volume ratio of the alpha-beta unsaturated cyano sulfonamide to the organic solvent is 11 mg/mL-110 mg/mL;
preferably, the mass ratio of the α - β unsaturated cyano sulfonamide to the base material is 1:0.5 to 1:5, a step of;
preferably, the mass ratio of the α - β unsaturated cyano sulfonamide to the base material is 1:1.5 to 1:2.5;
preferably, the mass ratio of the α - β unsaturated cyano sulfonamide to the trimethylnitrile silane is 1:0.1 to 1:5, a step of;
preferably, the mass ratio of the α - β unsaturated cyano sulfonamide to the trimethylnitrile silane is 1:0.5 to 1:1.3;
preferably, the reaction conditions are as follows:
the temperature is 0-100 ℃;
the time is 0.5 to 24 hours.
7. The pyrrolopyrimidine compound is characterized by having a structure shown in a formula II:
R 4 、R 5 、R 6 independently selected from C 1 ～C 13 Alkyl, C 6 ～C 20 Aryl, C 2 ～C 20 Heteroaryl, substituted C 1 ～C 13 Alkyl, substituted C 6 ～C 20 Aryl, substituted C 2 ～C 20 Heteroaryl;
preferably, R 4 、R 5 、R 6 Independently selected from C 1 ～C 7 Alkyl, C 6 ～C 10 Aryl, C 2 ～C 10 Heteroaryl, substituted C 1 ～C 7 Alkyl, substituted C 6 ～C 10 Aryl, substituted C 2 ～C 10 Heteroaryl;
preferably, substituted C 1 ～C 13 The substituent of the alkyl group being R d ；
The R is d Independently selected from deuterium atoms, halogens, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 13 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 13 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 13 Aryl phosphine, -CN, -NO 2 At least one of (a) and (b);
preferably, substituted C 6 ～C 20 The substituent of the aryl group is R e ；
The R is e Selected from deuterium atoms, halogens, C 1 ～C 13 Alkyl, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 20 Heteroaryl, C 2 ～C 20 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 20 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 20 Aryl phosphine, thioalkyl, sulfonyl, -CN, -NO 2 At least one of (a) and (b);
preferably, substituted C 2 ～C 20 Heteroaryl has R as substituent f ；
The R is f Independently selected from deuterium atoms, halogens, C 1 ～C 13 Alkyl, C 1 ～C 13 Polyfluoroalkyl, C 2 ～C 13 Alkenyl, C 2 ～C 13 Alkynyl, C 3 ～C 6 Cycloalkyl, C 2 ～C 20 Heterocyclyl, C 1 ～C 13 Oxo alkyl, C 6 ～C 20 Oxo-aryl, boric acid group, silane group, C 1 ～C 13 Alkyl phosphine, C 6 ～C 20 Aryl phosphine, -CN, -NO 2 At least one of (a) and (b);
preferably, the structural formula of the compound represented by formula ii is selected from the following compounds:
the pyrrolopyrimidine compound is prepared from the 2-aminopyrrole compound according to any one of claims 1 to 3 and/or the 2-aminopyrrole compound obtained by the preparation method according to any one of claims 4 to 6.
8. The preparation method of the pyrrolopyrimidine compound is characterized by comprising the following steps:
reacting a mixture containing 2-aminopyrrole compounds, diketones and solvents under an inactive gas to obtain pyrrolopyrimidine compounds;
preferably, the diketone is selected from one of 2, 6-dimethyl-3, 5-heptanedione and acetylacetone;
preferably, the solvent is selected from one of glacial acetic acid, a mixture of glacial acetic acid and water;
preferably, the volume ratio of the glacial acetic acid to the water mixture is 1:1;
preferably, the inactive gas is selected from one of nitrogen, argon and helium;
preferably, the ratio of the amount of 2-aminopyrrole compound to the amount of diketone is 1:1-1:10;
preferably, the reaction conditions are as follows:
the temperature is 15-125 ℃;
the time is 0.5 to 48 hours.
9. Use of a 2-aminopyrrole compound according to claims 1 to 3 and/or a 2-aminopyrrole compound according to claims 4 to 6 in the preparation of a pyrrolopyrimidine compound.
10. The use of the pyrrolopyrimidine compounds of claim 7 and/or the pyrrolopyrimidine compounds of claim 8 as fluorescent molecules or in medicaments.
CN202210301956.XA 2022-03-24 2022-03-24 2-aminopyrrole compound and preparation method and application thereof Pending CN116836100A (en)

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