WO2018099416A1 - Azo-compound, polymer and preparation method and use of same - Google Patents

Abstract

Provided in the present invention are an azo-compound, a polymer and a preparation method and a use. The structural formula of the azo-compound is shown in formula (I), wherein R¹、R²、R³ and m have meanings as described in the description. The azo-compound has a good blue light intercepting property, and the above compound is a polymerizable azo-compound that is not easily migrated and diffused in the polymer.

Description

Azo compound, polymer and preparation method and use thereof Technical field

The present invention relates to the field of ocular medical devices, and in particular to an azo compound, a polymer obtained by polymerizing the azo compound, and a preparation method and use thereof.

Background technique

In recent years, with the popularization and development of electronic display devices, the blue portion of visible light has attracted more and more attention to the damage of the human eye, especially the retina. Studies have shown that blue light in visible light can cause damage to the human eye, especially the retina, leading to decreased vision or even blindness. Therefore, in an ophthalmic medical device such as an eyeglass lens, a film capable of intercepting blue light or a component capable of intercepting blue light is added to prevent blue light from injuring the human eye.

However, current ophthalmic medical devices with blue-blocking capabilities and polymers for the preparation of ophthalmic medical devices remain to be improved.

Summary of the invention

This application is based on the discovery and recognition of the following facts and issues by the inventors:

Although eyeglass lenses with blue-light interception function are more common, in the eye medical devices such as intraocular lenses that are directly in contact with the human eye, products with blue-light interception function are still relatively rare. The inventors have found through in-depth research that this is mainly due to the interception function of blue light, which is generally achieved by adding a yellow dye having a blue light absorbing function to an eye medical device. In the above-mentioned eye medical device that is directly in contact with the human eye, the yellow dye required to be added cannot be diffused and migrated in the ophthalmic medical device, that is, it is required to ensure that the added yellow dye is stably present in the above-mentioned eye medical treatment. In the device, it will not enter the human eye in order to ensure the safety performance of the above-mentioned eye medical device. The yellow dyes that meet the above requirements are very limited, thus limiting the development of ophthalmic medical devices with blue-blocking capabilities.

The present invention aims to solve at least one of the technical problems in the related art at least to some extent. To this end, the present invention provides an azo compound which has good blue-blocking property, and the above compound is a polymerizable azo compound, which is difficult to migrate and diffuse in a polymer, and thus can be used as an artificial crystal or the like. Use of blue light absorbers in ocular medical devices.

The present invention also proposes a polymer containing the above azo compound and thus having a function of intercepting blue light. And the above azo compound is a polymerizable compound, and thus the above azo compound is not easily produced in the polymer proposed by the present invention. Raw diffusion migration.

The invention also provides the use of the polymers of the invention in the preparation of ocular medical devices. The use of the above polymer to prepare an ocular medical device can realize the interception function of blue light without affecting the use function of the ocular medical device, and has better safety.

Furthermore, the invention also proposes a process for the preparation of the polymers of the invention.

DRAWINGS

Figure 1 shows a comparison of the spectral transmittances of the polymers A3, A5, A10 and A0 of the present invention;

Figure 2 is a graph showing the spectral transmittance of the polymers A4, A8, A11 and A0 of the present invention;

Figure 3 is a graph showing the spectral transmittance of the polymers A1, A6, A9 and A0 of the present invention;

Figure 4 is a graph showing the comparison of spectral transmittances of the polymers A4 and A11 of the present invention before and after extraction;

Figure 5 is a graph showing the ratio of spectral absorption loss at 450 nm before and after extraction of the polymers A1, A2, A4, A6, A9, and A11 of the present invention.

Detailed description of the invention

Definitions and general terms

Embodiments of the invention are described in detail below, examples of which are illustrated in the accompanying drawings. The embodiments described below with reference to the drawings are intended to be illustrative of the invention and are not to be construed as limiting.

Unless otherwise stated, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those skilled in the art. All patents and publications related to the present invention are hereby incorporated by reference in their entirety. The term "comprising" or "including" is an open-ended expression that includes the content of the invention, but does not exclude other aspects. In the present invention, all numbers disclosed herein are approximate, whether or not the words "about" or "about" are used. The value of each number may have a difference of less than 10% or a reasonable difference considered by those in the field, such as a difference of 1%, 2%, 3%, 4% or 5%.

In the present invention, the azo compound proposed by the present invention has the formula of the formula (Ia) or the formula (I), and also includes the stereoisomer of the compound of the formula (Ia) or the formula (I). Or tautomer. "Stereoisomer" refers to a compound that has the same chemical structure but differs in the way the atoms or groups are spatially aligned. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotomers), geometric isomers (cis/trans) isomers, and atropisomers and the like.

The stereochemical definitions and rules used in the present invention generally follow SP Parker, Ed., McGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., "Stereochemistry Of Organic Compounds", John Wiley & Sons, Inc., New York, 1994 The stereochemical definitions and rules described.

Many organic compounds exist in optically active forms, i.e., they have the ability to rotate a plane of plane polarized light. In describing optically active compounds, the prefixes D and L, or R and S are used to indicate the absolute configuration of the molecule with respect to one or more of its chiral centers. The prefixes d and l or (+) and (-) are symbols for specifying the rotation of plane polarized light caused by the compound, wherein (-) or l indicates that the compound is left-handed. Compounds prefixed with (+) or d are dextrorotatory. A particular stereoisomer is an enantiomer and a mixture of such isomers is referred to as a mixture of enantiomers. A 50:50 mixture of enantiomers is referred to as a racemic mixture or a racemate, which can occur when there is no stereoselectivity or stereospecificity in a chemical reaction or process.

Any asymmetric atom (e.g., carbon, etc.) of the compounds disclosed herein may exist in racemic or enantiomerically enriched form, such as the (R)-, (S)- or (R, S)-configuration presence. In certain embodiments, each asymmetric atom has at least 50% enantiomeric excess in the (R)- or (S)-configuration, at least 60% enantiomeric excess, at least 70% enantiomeric excess, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess, or at least 99% enantiomeric excess.

Depending on the choice of starting materials and methods, the compounds of the invention may be one of the possible isomers or mixtures thereof, such as racemates and mixtures of diastereomers (depending on the number of asymmetric carbon atoms) The form exists. Optically active (R)- or (S)-isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may be in the E or Z configuration; if the compound contains a disubstituted cycloalkyl group, the substituent of the cycloalkyl group may have a cis or trans configuration.

The resulting mixture of any stereoisomers can be separated into pure or substantially pure geometric isomers, enantiomers, diastereomers, for example, by chromatography, depending on the difference in physicochemical properties of the components. Method and / or step crystallization.

The racemate of any of the resulting end products or intermediates can be resolved into the optical antipodes by methods known to those skilled in the art by known methods, for example, by obtaining the diastereomeric salts thereof. Separation. Racemic products can also be separated by chiral chromatography, such as high performance liquid chromatography (HPLC) using a chiral adsorbent. In particular, enantiomers can be prepared by asymmetric synthesis, for example, see Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Principles of Asymmetric Synthesis (2 ^nd Ed. Robert) E. Gawley, Jeffrey Aubé, Elsevier, Oxford, UK, 2012); Eliel, ELStereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, SHTables of Resolving Agents and Optical Resolutions p. 268 (ELEliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972); Chiral Separation Techniques: A Practical Approach (Subramanian, G. Ed., Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2007).

The term "tautomer" or "tautomeric form" means a low energy barrier with different energies (low energy) Barrier) A structural isomer that is converted to each other. If tautomerism is possible (as in solution), the chemical equilibrium of the tautomers can be achieved. For example, proton tautomers (also known as prototropic tautomers) include interconversions by proton transfer, such as keto-enol isomerization and imine-ene Amine isomerization. Valence tautomers include interconversions by recombination of some bonding electrons. A specific example of keto-enol tautomerization is the interconversion of a pentane-2,4-dione and a 4-hydroxypent-3-en-2-one tautomer. Another example of tautomerization is phenol-keto tautomerization. A specific example of phenol-keto tautomerization is the interconversion of pyridin-4-ol and pyridine-4(1H)-one tautomers. All tautomeric forms of the compounds of the invention are within the scope of the invention unless otherwise indicated.

In the present invention, the term "blue light" refers to visible light having a wavelength in the range of 400 to 550 nm, and the terms "intercepting blue light" and "absorbing blue light" refer to a substance such as an azo compound or a polymer proposed by the present invention when visible light containing blue light is contained. When the surface of the formed material is incident on one side and passes through the material, the intensity of blue light in the outgoing light on the other side of the material is significantly lower than that of the blue light in the incident light, and even the emitted light does not contain blue light. . The "room temperature" in the present invention refers to a temperature which can be attained by subjecting, for example, a reaction liquid, a mixed liquid or the like to an indoor environment for a certain period of time during the synthesis, preparation, and the like without performing additional cooling or heat treatment. For example, in some embodiments, the "room temperature" temperature is from about 10 degrees Celsius to about 40 degrees Celsius. In some embodiments, "room temperature" refers to a temperature of from about 20 degrees Celsius to about 30 degrees Celsius; in other embodiments, "room temperature" refers to 20 degrees Celsius, 22.5 degrees Celsius, 25 degrees Celsius, 27.5 degrees Celsius, and the like.

In the present invention, the term "optional" or "optionally" means that the subsequently described event or situation may, but does not necessarily, occur, and the description includes the case in which the event or situation occurs and in which it does not occur. . For example, "optionally substituted alkylene" means that the alkylene group may be unsubstituted by any substituent, or alkyl, halogen, nitro, cyano, aldehyde, amino, alkoxy, haloalkyl, haloalkane Substituted by a substituent such as an oxy group.

In each part of the specification, the substituents of the compounds disclosed herein are disclosed in terms of the type or range of groups. In particular, the invention includes each individual sub-combination of each member of the group and range of such groups. For example, the term "C ₁ -C ₆ alkyl" refers particularly to the disclosure independently methyl, ethyl, C ₃ alkyl, C ₄ alkyl, C ₅ alkyl, and C ₆ alkyl.

The term "alkyl" or "alkyl group" denotes a saturated straight or branched chain hydrocarbyl group. In one embodiment, the alkyl group contains from 1 to 20 carbon atoms; in another embodiment, the alkyl group contains from 1 to 12 carbon atoms; in another embodiment, the alkyl group contains 1 -8 carbon atoms; in yet another embodiment, the alkyl group contains 1-6 carbon atoms; and in one embodiment, the alkyl group contains 1-3 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl (Me, -CH ₃ ), ethyl (Et, -CH ₂ CH ₃ ), n-propyl (n-Pr, -CH ₂ CH ₂ CH ₃ ), isopropyl (i-Pr, -CH(CH ₃ ) ₂ ), n-butyl (n-Bu, -CH ₂ CH ₂ CH ₂ CH ₃ ), isobutyl (i-Bu, -CH ₂ CH) (CH ₃ ) ₂ ), sec-butyl (s-Bu, -CH(CH ₃ )CH ₂ CH ₃ ), tert-butyl (t-Bu, -C(CH ₃ ) ₃ ), n-pentyl (-CH) ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-pentyl (-CH(CH ₃ )CH ₂ CH ₂ CH ₃ ), 3-pentyl (-CH(CH ₂ CH ₃ ) ₂ ), 2-methyl -2-butyl (-C(CH ₃ ) ₂ CH ₂ CH ₃ ), 3-methyl-2-butyl (-CH(CH ₃ )CH(CH ₃ ) ₂ ), 3-methyl-1- Butyl (-CH ₂ CH ₂ CH(CH ₃ ) ₂ ), 2-methyl-1-butyl (-CH ₂ CH(CH ₃ )CH ₂ CH ₃ ), n-hexyl (-CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-hexyl (-CH(CH ₃ )CH ₂ CH ₂ CH ₂ CH ₃ ), 3-hexyl (-CH(CH ₂ CH ₃ )(CH ₂ CH ₂ CH ₃ )), 2-methyl-2-pentyl (-C(CH ₃ ) ₂ CH ₂ CH ₂ CH ₃ ), 3-methyl-2-pentyl (-CH(CH ₃ )CH(CH ₃ )CH ₂ CH ₃ ), 4-methyl-2-pentyl (-CH(CH ₃ )CH ₂ CH(CH ₃ ) ₂ ), 3-methyl-3-pentyl (-C(CH ₃ )(CH ₂ CH ₃ ) ₂ ), 2-methyl-3-pentyl (-CH(CH ₂ CH ₃ )CH(CH ₃ ) ₂ ), 2,3-dimethyl 2-butyl (-C(CH ₃ ) ₂ CH(CH ₃ ) ₂ ), 3,3-dimethyl-2-butyl (-CH(CH ₃ )C(CH ₃ ) ₃ ), positive Heptyl, n-octyl, and so on.

The term "alkylene" denotes a saturated divalent hydrocarbon radical derived from the removal of two hydrogen atoms from a saturated straight or branched chain hydrocarbon. In one embodiment, the alkylene group contains from 1 to 12 carbon atoms. In another embodiment, the alkylene group contains 1-6 carbon atoms; in another embodiment, the alkylene group contains 1-4 carbon atoms; in yet another embodiment, the alkylene group The group contains 1-3 carbon atoms; also in one embodiment, the alkylene group contains 1-2 carbon atoms. Non-limiting examples include methylene (-CH ₂ -), ethylene (-CH ₂ CH ₂ -), isopropylidene (-CH(CH ₃ )CH ₂ -), and the like.

The terms "heteroalkylene" and "heteroalkylene chain" mean that one or more heteroatoms such as O, N, S, etc. may be inserted into the alkylene and alkylene chains, and/or, optionally one Or a plurality of -CH ₂ - is replaced by a group such as -NH-, -C(=O), -S(=O), -S(=O) ₂ , wherein the alkylene group and the alkylene chain have the same The meaning of the invention. Unless otherwise specified, a heteroalkylene or heteroalkylene chain contains from 1 to 12 carbon atoms, and in some embodiments, a heteroalkylene group contains from 1 to 10 carbon atoms, and in other embodiments, a heteroaza The alkyl group contains from 1 to 5 carbon atoms, and in other embodiments, the heteroalkylene group contains from 1 to 4 carbon atoms. Such examples include, but are not limited to, -CH ₂ -O-, -CH ₂ -O-CH ₂ -, -C(CH ₃ ) ₂ -O-, -C(CH ₃ )(OH)-O- , -CH(CH ₃ )-O-CH ₂ -, -C(CH ₃ ) ₂ -O-CH ₂ -, -CH ₂ -NH-, -CH ₂ -NH-CH ₂ -, -C(CH _{3 2} -NH-, -CH(CH ₃ )-NH-CH ₂ -, -C(CH ₃ ) ₂ -NH-CH ₂ -, -C(CH ₃ )(OH)-NH-, -C(= O) -NH-, -C(=O)-NH-CH ₂ -, -CH ₂ -NH-C(=O)-. Wait.

The term "alkenyl" denotes a straight or branched chain hydrocarbon radical having at least one carbon-carbon sp ² double bond, which includes the positioning of "cis" and "tans", or the positioning of "E" and "Z". In one embodiment, the alkenyl group contains 2-20 carbon atoms; in another embodiment, the alkenyl group contains 2-12 carbon atoms; in yet another embodiment, the alkenyl group comprises 2 -8 carbon atoms; also in one embodiment, the alkenyl group contains 2-6 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl (-CH = CH _2), allyl (-CH ₂ CH = CH ₂₎ and the like.

The term "alkynyl" denotes a straight or branched chain hydrocarbon radical having at least one carbon-carbon sp triple bond. In one embodiment, the alkynyl group contains 2-20 carbon atoms; in another embodiment, the alkynyl group contains 2-12 carbon atoms; in yet another embodiment, the alkynyl group comprises 2 -8 carbon atoms; also in one embodiment, the alkynyl group contains 2-6 carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl (-C≡CH), propargyl (-CH ₂ C≡CH), 1-propynyl (-C≡C-CH ₃ ), and the like. .

The term "alkoxy" denotes an alkyl group attached to the remainder of the molecule through an oxygen atom, wherein the alkyl group has the meaning as described herein. Unless otherwise specified, the alkoxy group contains from 1 to 12 carbon atoms. In one embodiment, the alkoxy group contains from 1 to 6 carbon atoms; in another embodiment, the alkoxy group contains from 1 to 4 carbon atoms; in yet another embodiment, the alkoxy group The group contains 1-3 carbon atoms. The alkoxy group is optionally substituted with one or more substituents described herein. Examples of alkoxy groups include, but are not limited to, methoxy (MeO, -OCH ₃ ), ethoxy (EtO, -OCH ₂ CH ₃ ), 1-propoxy (n-PrO, n- Propyloxy, -OCH ₂ CH ₂ CH ₃ ), 2-propoxy (i-PrO, i-propoxy, -OCH(CH ₃ ) ₂ ), and the like.

The term "alkylthio" refers to a _C1-6 straight or branched alkyl group attached to the remainder of the molecule through a sulfur atom. In one embodiment, the lower alkylthio is C _1-4 alkylthio level, such examples include, but are not limited to methylthio (CH ₃ S-).

The term "alkylamino" or "alkylamino" includes "N-alkylamino" and "N,N-dialkylamino", wherein the amino groups are each independently substituted with one or two alkyl groups, Wherein the alkyl group has the meaning as described herein. In one embodiment, the alkylamino group is a lower alkylamino group to which one or two _C1-6 alkyl groups are attached to the nitrogen atom. In another embodiment, the alkylamino group is a lower alkylamino group of _C1-4 . Suitable alkylamino groups may be monoalkylamino or dialkylamino, examples of which include, but are not limited to, N-methylamino, N-ethylamino, N,N-dimethylamino, N, N - Diethylamino and the like. The alkylamino group is optionally substituted with one or more substituents described herein.

The terms "halogen" and "halo" refer to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

The term "haloalkyl", "haloalkenyl" or "haloalkoxy" denotes an alkyl, alkenyl or alkoxy group, respectively, substituted by one or more halogen atoms, wherein alkyl, alkenyl and alkoxy The radicals have the meanings described herein, and such examples include, but are not limited to, difluoromethyl, trifluoromethyl, trifluoromethoxy, 2,2,2-trifluoroethoxy, 2 , 2,3,3-tetrafluoropropoxy, and the like. The haloalkyl, haloalkenyl or haloalkoxy group is optionally substituted with one or more substituents described herein.

The term "alkoxyalkyl" denotes an alkyl group substituted by one or more alkoxy groups, wherein the alkyl group and the alkoxy group have the meanings as described herein, such examples include However, it is not limited to methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl and the like.

The term "aryl" denotes a monocyclic, bicyclic and tricyclic carbocyclic ring system containing from 6 to 14 ring atoms, or from 6 to 12 ring atoms, or from 6 to 10 ring atoms, wherein at least one ring system is aromatic Of the family, wherein each ring system comprises a ring of 3-7 atoms and one or more attachment points are attached to the remainder of the molecule. Examples of the aryl group may include a phenyl group, a naphthyl group, and an anthracenyl group. When the aryl group may be optionally substituted, the substituted group may be fluorine, chlorine, bromine, iodine, cyano, azide, nitro, amino, hydroxy, decyl, alkylamino, alkoxy, alkylthio, Alkyl, haloalkyl, alkenyl, alkyne A group, a carbocyclic group, a heterocyclic group, an aryl group or a heteroaryl group.

The term "arylalkyl" denotes an alkyl group substituted with one or more aryl groups; wherein the alkyl group and the aryl group have the meaning as described herein, and examples of arylalkyl include , but not limited to, benzyl, phenethyl and the like.

The term "aryloxy" or "aryloxy" refers to an optionally substituted aryl group, as defined herein, attached to an oxygen atom and attached to the remainder of the molecule by an oxygen atom, wherein the aryl group Has the meaning as described in the present invention. Examples of aryloxy groups include, but are not limited to, phenoxy, halophenoxy, cyano substituted phenoxy, hydroxy substituted phenoxy, and the like.

The term "aryloxyalkyl" refers to an alkyl group substituted with one or more aryloxy groups; wherein the aryloxy group and the alkyl group have the meanings as described herein. Examples of aryloxyalkyl groups include, but are not limited to, phenoxymethyl, fluorophenoxymethyl (such as (2-fluorophenoxy)methyl, (3-fluorophenoxy)methyl or (4-Fluorophenoxy)methyl), chlorophenoxymethyl, and the like.

The term "arylalkoxy" denotes that the alkoxy group is substituted by one or more aryl groups; wherein the alkoxy group and the aryl group have the meanings as described herein. Examples of arylalkoxy groups include, but are not limited to, benzyloxy, fluorobenzyloxy, chlorobenzyloxy, cyano substituted benzyloxy, methylsulfonyl substituted benzyloxy, phenylethoxy Base, and so on.

Detailed content of the invention

In one aspect of the invention, the invention provides an azo compound. The azo compound has a compound of the formula represented by the formula (Ia) or a stereoisomer or tautomer of a compound of the formula: (Ia):

among them,

R ¹ is hydrogen or alkyl; R ² is alkyl;

X is O, NH or NR ⁵ ; Y is O, S, NH or NR ⁵ ; wherein each R ^{5 is} independently C _1-10 alkyl;

W is a single bond, an alkylene group or a heteroalkylene group; W is optionally 1, 2, 3, 4 or 5 fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, oxygen Substituted (=O), C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylthio or C _1-6 alkylamino;

R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR ^a R ^b , -C(=O)R ^c , -S(=O ₂ -R ^c , -C(=O)-NR ^a R ^b , -S(=O) ₂ -NR ^a R ^b , C _1-6 alkyl, C _1-6 alkoxy, halogen C _{1 -6} alkyl, halo C _1-6 alkoxy, C _1-6 alkoxy C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-12 aryl, C _6-12 aryl C _1-6 alkyl, C _6-12 aryloxy, C _6-12 aryloxy C _1-6 alkyl or C _6-12 aryl C _1-6 alkoxy;

Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-6 alkyl group;

n is 0, 1, 2, 3 or 4;

m is 0, 1, 2, 3, 4 or 5.

In some embodiments, R ¹ is hydrogen or C _1-4 alkyl. In other embodiments, R ¹ is hydrogen or methyl.

In some embodiments, R ² is alkyl. In other embodiments, R ² is C _1-6 alkyl. In still other embodiments, R ² is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl.

In some embodiments, X is O, NH or NR ⁵ . In other embodiments, X is O or NH.

In some embodiments, Y is O, S, NH or NR ⁵ . In other embodiments, Y is O, S or NH.

In some embodiments, each R ^{5 is} independently C _1-10 alkyl.

In some embodiments, W is a single bond, an alkylene or a heteroalkylene group; W is optionally 1, 2, 3, 4 or 5 fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro Substituted by amino, carboxyl, oxo (=O), C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylthio or C _1-6 alkylamino.

In other embodiments, W is a single bond, C _1-12 alkylene or C _1-12 heteroalkylene; W is optionally 1, 2, 3, 4 or 5 fluoro, chloro, bromo, iodo , hydroxy, cyano, nitro, amino, carboxy, oxo (=O), C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylthio or C _1-6 alkylamino Replace.

In still other embodiments, W is -(CR ^d R ^e ) _r -, -(CR ^d R ^e ) _r -O-(CR ^f R ^g ) _t -, -(CR ^d R ^e ) _r -C( =O)-(CR ^f R ^g ) _t -, -(CR ^d R ^e ) _r -N(R ^h )-(CR ^f R ^g ) _t -, -C(=O)-N(R ^h )- (CR ^f R ^g ) _t -, -(CR ^d R ^e ) _r -N(R ^h )-C(=O)- or -(CR ^d R ^e ) _r -N(R ^h )-S(=O ) ₂ -;

Each r is independently 1, 2, 3 or 4;

Each t is independently 0, 1, 2 or 3;

Each of R ^d , R ^e , R ^f and R ^{g is} independently hydrogen, deuterium, fluorine, chlorine, bromine, iodine, cyano, hydroxy, nitro, amino, carboxy, oxo (=O), C _1-4 An alkyl group, a C _2-4 alkenyl group, a C _2-4 alkynyl group, a C _1-3 alkoxy group or a C _1-3 alkylamino group;

Each R ^{h is} independently hydrogen, C _1-4 alkyl, C _2-4 alkenyl or C _2-4 alkynyl.

In some further embodiments, W is _{-CH 2 -, - (CH 2} ) 2 -, - C (CH 3) 2 -, - CH 2 -C (CH 3) 2 -, - C (CH 3) ( OH)-, -CH ₂ -O-, -CH ₂ -O-CH ₂ -, -C(CH ₃ ) ₂ -O-, -C(CH ₃ )(OH)-O-, -CH(CH ₃ -O-CH ₂ -, -C(CH ₃ ) ₂ -O-CH ₂ -, -CH ₂ -NH-, -CH ₂ -NH-CH ₂ -, -C(CH ₃ ) ₂ -NH-, -CH(CH ₃ )-NH-CH ₂ -, -C(CH ₃ ) ₂ -NH-CH ₂ -, -C(CH ₃ )(OH)-NH-, -C(=O)-NH-, -C(=O)-NH-CH ₂ -, -CH ₂ -NH-C(=O)-.

In some embodiments, R ^3, R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxyl, aldehyde, nitro, ^{cyano, -NR a R b, -C (} = O) R c , -S(=O) ₂ R ^c , -C(=O)NR ^a R ^b , -S(=O) ₂ NR ^a R ^b , C _1-6 alkyl, C _1-6 alkoxy, halogen C _1-6 alkyl, halo C _1-6 alkoxy, C _1-6 alkoxy C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-12 Aryl, C _6-12 aryl C _1-6 alkyl, C _6-12 aryloxy, C _6-12 aryloxy C _1-6 alkyl or C _6-12 aryl C _1-6 alkoxy Base; and

Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-6 alkyl group.

In some embodiments, R ^3, R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxyl, aldehyde, nitro, ^{cyano, -NR a R b, -C (} = O) R c , -S(=O) ₂ R ^c , -C(=O)NR ^a R ^b , -S(=O) ₂ NR ^a R ^b , C _1-4 alkyl, C _1-4 alkoxy, halogen C _1-4 alkyl, halo C _1-4 alkoxy, C _1-4 alkoxy C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _6-10 Aryl, C _6-10 aryl C _1-4 alkyl, C _6-10 aryloxy, C _6-10 aryloxy C _1-4 alkyl or C _6-10 aryl C _1-4 alkoxy base;

Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-4 alkyl group. In some embodiments, R ³ , R ⁴ are each independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, aldehyde, nitro, cyano, —NH ₂ , —N(CH ₃ ) ₂ , —C (=O)CH ₃ , -C(=O)OH, -C(=O)OCH ₃ , -CONH ₂ , -CON(CH ₃ ) ₂ , methyl, ethyl, n-propyl, isopropyl, n-Butyl, isobutyl, tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, trifluoromethyl, trifluoromethoxy , trifluoroethyl, trifluoroethoxy, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, phenyl Phenylmethyl, phenethyl, phenylpropyl, phenoxy, phenoxymethyl, phenoxyethyl, phenylmethoxy or phenylethoxy.

In some embodiments, the invention provides an azo compound. The azo compound has a compound conforming to the formula of the formula (I) or a stereoisomer or tautomer of a compound of the formula represented by the formula (I).

In formula (I), R ¹ is H or alkyl; R ² is alkyl; R ^{3 is} independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, aldehyde, nitro, cyano, -NR ^a R ^b , -C(=O)R ^c , -S(=O) ₂ R ^c , -C(=O)NR ^a R ^b , -S(=O) ₂ NR ^a R ^b , alkyl, alkane Oxy, halo C _1-6 alkyl, halo C _1-6 alkoxy, C _1-6 alkoxy C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-12 aryl, C _6-12 aryl C _1-6 alkyl, C _6-12 aryloxy, C _6-12 aryloxy C _1-6 alkyl or C _6-12 aryl C _{1 -6} alkoxy; and

Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-6 alkyl group;

m is 0, 1, 2, 3, 4 or 5.

The azo compound having the above structure is a polymerizable yellow dye which can exhibit a good blue light absorption/interception function and can be formed with other materials (for example, monomers or additives for forming an ophthalmic medical device such as an artificial lens). The copolymer, thus reducing the risk of migration of the above azo compounds in ophthalmic medical devices, can be used to prepare ophthalmic medical devices with blue light blocking capabilities.

In one embodiment of the invention, R ¹ is H or alkyl; in another embodiment, R ¹ is H or C _1-6 alkyl; in yet another embodiment, R ¹ is H or methyl .

In one embodiment of the invention, R ² is alkyl; in another embodiment, R ² is C _1-6 alkyl; in another embodiment, R ² is methyl, ethyl, n-propyl Base, isopropyl, n-butyl or isobutyl.

In an embodiment of the invention, m is 0, 1, 2, 3, 4 or 5,

R ^{3 is} independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR ^a R ^b , -C(=O)R ^c , -S(=O) ₂ R ^c , -C(=O)NR ^a R ^b , -S(=O) ₂ NR ^a R ^b , C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkyl, halogen C _1-6 alkoxy, C _1-6 alkoxy C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-12 aryl, C _6-12 aryl C _1-6 alkyl, C _6-12 aryloxy, C _6-12 aryloxy C _1-6 alkyl or C _6-12 aryl C _1-6 alkoxy;

Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-6 alkyl group.

In another embodiment, m is 0, 1, 2, ³ , 4 or 5, and R ^{3 is} independently hydrogen, fluoro, chloro, bromo, iodo, hydroxy, aldehyde, nitro, cyano, -NR, respectively. ^a R ^b , -C(=O)R ^c , -S(=O) ₂ R ^c , -C(=O)NR ^a R ^b , -S(=O) ₂ NR ^a R ^b , C _1-4 Alkyl, C _1-4 alkoxy, halo C _1-4 alkyl, halo C _1-4 alkoxy, C _1-4 alkoxy C _1-4 alkyl, C _2-4 alkenyl , C _2-4 alkynyl, C _6-10 aryl, C _6-10 aryl C _1-4 alkyl, C _6-10 aryloxy, C _6-10 aryloxy C _1-4 alkyl or C _6-10 aryl C _1-4 alkoxy; and

Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-4 alkyl group.

In still other embodiments, m is 0, 1, 2, ³ , 4 or 5, and R ^{3 is} independently hydrogen, fluoro, chloro, bromo, iodo, cyano, hydroxy, nitro, aldehyde, -NH, respectively. ₂ , -N(CH ₃ ) ₂ , -C(=O)CH ₃ , -C(=O)OH, -C(=O)OCH ₃ , -CONH ₂ , -CON(CH ₃ ) ₂ , methyl , ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy Base, trifluoromethyl, trifluoromethoxy, trifluoroethyl, trifluoroethoxy, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxy Ethyl ethyl, ethoxypropyl, phenyl, benzyl, phenethyl, phenylpropyl, phenoxy, phenoxymethyl, phenoxyethyl, benzyloxy or phenylethoxy.

In one embodiment of the invention, R ¹ is H or methyl, R ² is methyl or ethyl, m is 1 or 2, and R ^{3 is} independently hydroxy, methyl, ethyl, n-propyl, Isopropyl, n-butyl, isobutyl, methoxy, ethoxy, methoxyethyl, trifluoromethyl, trifluoromethoxy, fluoro, chloro or bromo.

In the above embodiment of the invention, the number and type of R ³ do not affect each other, and when m is greater than 1, a plurality of R ³ in the azo compound may be the same or different.

In another embodiment of the present invention, the azo compound of the present invention may be a compound satisfying the formula represented by the following formulas (1) to (20), or a stereoisomer of a compound satisfying the following formula: Bulk or tautomer:

a compound satisfying the formula represented by the above formulas (1) to (20), or a stereoisomer of a compound satisfying the above formula The azo compound of the body or tautomer has an ideal blue-blocking effect and can be added as a blue light absorber to the raw material of the synthetic ocular medical device. The above azo compounds are all polymerizable azo compounds, and the inventors have found through extensive experiments that the above azo compounds can be polymerized with other raw materials forming an ocular medical device when preparing an ocular medical device, thereby being relatively stable. It is present in the obtained ophthalmic medical device, which in turn can greatly reduce the risk of entering the human eye due to migration of the azo compound during use. Moreover, the above compounds do not adversely affect the optical properties (refractive index, spectral transmittance, etc.), mechanical properties (tensile strength, elongation at break, elastic modulus, etc.) of the ocular medical device, and thus can be used for A flexible ophthalmic medical device such as a foldable intraocular lens is prepared.

In another aspect, the invention provides a polymer. The monomer constituting the polymer includes a bulk monomer and a blue light absorber, which is an azo compound previously described in the present invention. In other words, the monomer constituting the polymer includes a monomer (bulk monomer) forming a polymer body and an azo compound previously proposed by the present invention. Thus, the polymer has the effect of intercepting blue light. Moreover, in the process of synthesizing the polymer, the blue light absorber can be copolymerized with the bulk monomer or other additives in the raw material for synthesizing the polymer, thereby greatly reducing the risk of migration of the blue light absorber inside the polymer. In turn, the safety of the device directly in contact with the human body prepared using the polymer can be improved. For example, the polymer can be used to prepare an ocular medical device such as an artificial lens, so that the ocular medical device can also have a function of intercepting blue light, thereby reducing the damage of blue light in visible light to an organ such as a human eye.

In the present invention, the ratio of the blue light absorber and the bulk monomer in the above polymer can be adjusted according to actual conditions. The term "bulk monomer" specifically refers to the primary monomer material used to form the polymer body. The bulk monomer is a main component capable of constituting the above-mentioned polymer proposed by the present invention by polymerization, which is capable of undergoing copolymerization with a blue light absorber during polymerization. Since the blue light absorber contains a polymerizable group, the monomers commonly used for forming the polymer can be copolymerized with the blue light absorber proposed by the present invention, and therefore, in the present invention, the specific type of the bulk monomer is not particularly limited. In some embodiments of the invention, the bulk monomer is an acrylate monomer, which may include, but is not limited to, at least one of the following monomers: methyl methacrylate, ethyl methacrylate, propyl methacrylate, Isopropyl methacrylate, butyl methacrylate, tert-butyl methacrylate, isobutyl methacrylate, amyl methacrylate, t-amyl methacrylate, hexyl methacrylate, glysyl methacrylate Ester, octyl methacrylate, 2-ethylhexyl methacrylate, decyl methacrylate, decyl methacrylate, dodecyl methacrylate, stearyl methacrylate, methacrylic acid Cyclopentyl ester, cyclohexyl methacrylate, phenoxy methacrylate; methoxyethyl methacrylate, ethoxyethyl methacrylate, ethoxyethyl acrylate, methoxy methacrylate Diethylene glycol ester, 2-ethylphenoxy methacrylate, 2-ethylphenoxy acrylate, 2-ethylthiophene methacrylate, 2-ethylthiophene acrylate, A 2-ethylaminophenyl acrylate, 2-ethylaminophenyl acrylate Phenyl methacrylate, benzyl methacrylate, 2-phenylethyl methacrylate, 2-phenylethyl acrylate, 3-phenylpropyl methacrylate, -4-benzene methacrylate Base Butyl ester, 4-methylphenyl methacrylate, 4-methylbenzyl methacrylate, 2,2-methylphenylethyl methacrylate, 2,3-methyl methacrylate Phenylethyl ester, 2,4-methylphenylethyl methacrylate, 2-(4-propylphenyl)ethyl methacrylate, 2-(4-(1-methyl) methacrylate Ethyl ethyl) phenyl) ethyl ester, 2-(4-methoxyphenyl)ethyl methacrylate, 2-(4-cyclohexylphenyl)ethyl methacrylate, methacrylic acid-2 -(2-chlorophenyl)ethyl ester, 2-(3-chlorophenyl)ethyl methacrylate, 2-(4-chlorophenyl)ethyl methacrylate, -2-(methacrylic acid) 4-bromophenyl)ethyl ester, 2-(3-phenylphenyl)ethyl methacrylate, 2-(4-phenylphenyl)ethyl methacrylate, methacrylic acid-2-( 4-benzylphenyl)ethyl ester. In other embodiments of the invention, the bulk monomer may comprise at least one of 2-phenylethyl acrylate, 2-phenylethyl methacrylate, and ethoxyethyl methacrylate. In other embodiments of the invention, the bulk monomer is a vinyl-based monomer, which may include, but is not limited to, at least one of the following monomers: styrene, 4-butylstyrene, styrene, vinyl acetate, 4-ethoxymethylstyrene, 4-hexyloxymethylstyrene, 4-hexyloxyethylstyrene, vinyl ether, n-butyl vinyl ether, isobutyl vinyl ether, uncle Butyl vinyl ether, cyclohexene vinyl ether, butanediol divinyl ether, N-vinyl caprolactam, dodecyl vinyl ether, octadecyl vinyl ether, divinyl glycol divinyl Ether ether, trivinyl glycol divinyl ether. In still other embodiments of the present invention, the bulk monomer is an allyl monomer, which may include, but is not limited to, at least one of the following monomers: methyl crotonate, ethyl crotonate, benzene crotonate. Ethyl ester, propylene acetate, propylene propionate, propylene butyrate, propylene valerate, propylene hexanoate, 3-phenyl-2-propenyl butyrate. The above bulk monomer has better optical and mechanical properties, and can further improve the performance of the polymer.

In the raw material constituting the polymer proposed by the present invention, at least one of a crosslinking agent, an ultraviolet absorber, and an initiator may be further included. The above crosslinking agent, ultraviolet absorber and initiator may be mixed with a bulk monomer and a blue light absorber to form a polymer of the present invention by polymerization. In an embodiment of the invention, the crosslinking agent may include, but is not limited to, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, 1,3-propanediol. Dimethacrylate, 1,6-hexanediol dimethacrylate, 1,3-butanediol dimethacrylate, 1,4-butanediol dimethacrylate, 1,4-butyl Diol diacrylate, trimethylolpropane trimethacrylate, 1,5-bis(methacryloyloxy)-2,2,3,3,4,4-hexafluorohexane, 1, 6-bis(acryloyloxy)-2,2,3,3,4,4,5,5-octafluorohexane and pentaerythritol tetraacrylate. UV absorbers may include, but are not limited to, 2-(2'-hydroxy-3'-methallyl-5'-methylphenyl)benzotriazole, 2-[3-(2H-benzotriazole) 2-yl)-4-hydroxyphenyl]ethyl 2-methacrylate, 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-propenyl)phenol , 2-(5-chloro-2H-benzo[d][1,2,3]triazole)-4-methyl-6-(2-allyl)phenol, 4-allyl-2- (5-Chloro-2H-benzo[d][1,2,3]triazole)-6-methoxyphenol, 2-(5-chloro-2H-1,2,3-benzo[d] [1,2,3]triazole)-4-methyl-6-allylphenol, 2-hydroxy-4-(methacryloyloxy)benzophenone, and 2-acrylic acid 2-(4- Benzoyl-3-hydroxyphenoxy)ethyl ester. Initiators may include, but are not limited to, benzoyl peroxide, t-butyl hydroperoxide, cumyl hydroperoxide, bis(4-tert-butylcyclohexyl)peroxydicarbonate, azobisisobutyronitrile, and even Nitrogen bis(2,4-dimethylvaleronitrile). Thereby, the performance of the polymer can be further improved.

In another aspect, the invention provides an ocular medical device. The ocular medical device comprises the polymer set forth above in the present invention. Thus, the ocular medical device has all of the features and advantages of the foregoing polymers and will not be described again. Specifically, the ocular medical device has ideal mechanical properties and optical properties, and can intercept blue light components in visible light, thereby reducing damage of blue light to organs such as the human eye. The ocular medical device has better safety performance, because the blue light absorbing agent in the polymer proposed by the invention is less likely to migrate and diffuse in the polymer, thereby preventing direct contact of the azo compound forming the blue absorbing agent with the human body. .

In an embodiment of the invention, the ocular medical device may be an intraocular lens, an intraocular lens, a contact lens, a corneal correction, an intracorneal lens, a corneal inlay, a corneal ring or a glaucoma filter.

In still another aspect, the invention provides a method of making the polymer of the invention. The raw material mixture is subjected to heat treatment or photocuring treatment. In some embodiments, the method includes subjecting the feedstock mixture to a gradient heat treatment to obtain a polymer. Among them, the raw material mixture contains the bulk monomer described above and a blue light absorber. The specific types of the bulk monomer and the blue light absorber have been described in detail above and will not be described herein. In the method proposed by the present invention, the ratio of the bulk monomer and the blue light absorber is also not particularly limited. Those skilled in the art can make adjustments to the above ratios according to the requirements of the physicochemical properties of the specific polymer prepared, as well as the specific types of bulk monomers and blue light absorbers selected. In order to further improve the properties of the polymer produced by the method, at least one of a crosslinking agent, an initiator, and an ultraviolet absorber may be further included in the raw material mixture. The method has simple operation steps, short production cycle, and the obtained polymer has ideal physical and chemical properties (such as optical and mechanical properties and intercepting blue light function).

In some embodiments, the gradient heating process described above can include:

The first reaction stage:

In the first reaction stage, the raw material mixture is heated to 40 to 120 degrees Celsius for the reaction, preferably at 40 to 70 degrees Celsius, and the reaction time may be from 1 to 48 hours. The reaction at a lower temperature prevents the reaction rate from being too fast, which is advantageous for forming a sample having a uniform appearance, thereby improving the performance of the polymer.

Second reaction stage:

In the second reaction stage, the raw material mixture passing through the first reaction stage is heated to 40 to 140 ° C for the reaction, preferably at 80 to 120 ° C, and the reaction time may be from 1 to 48 hours. Thereby, it is advantageous to promote further reaction of the remaining raw materials, increase the conversion rate of the raw materials, and further improve the properties of the polymer prepared by the method.

The solution of the present invention will be explained below in conjunction with the embodiments. Those skilled in the art will appreciate that the following examples are merely illustrative of the invention and are not to be considered as limiting the scope of the invention. Where specific techniques or conditions are not indicated in the examples, they are carried out according to the techniques or conditions described in the literature in the art or in accordance with the product specifications. The reagent or instrument used is not marked Ming manufacturers are all conventional products that can be obtained through commercial purchase.

The examples described below are all set to degrees Celsius unless otherwise stated. The reagents used are all commercially available or can be prepared by the methods described herein.

In the present invention, if there is any difference between the chemical name and the chemical structure, the structure is dominant.

The following abbreviations are used throughout the present invention.

g g

mL ml

Mm mmol

h hours

Min minute

s seconds

Boc tert-butoxycarbonyl

EtOAc ethyl acetate

n-Hex n-hexane

Wt% wt%

Example 1

1-(4-((4-hydroxyphenyl)diazenyl)phenoxy)-3-methoxypropan-2-yl methacrylate

Step 1: Synthesis of the compound 1-(4-nitrophenoxy)-3-methoxypropan-2-ol

4-Nitrophenol (41.7 g, 0.3 mol), potassium carbonate (56.5 g, 0.1 mol) and absolute ethanol (200 mL) were successively added to a three-necked flask, and the mixture was stirred under reflux for 1 hour, and then slowly added dropwise thereto 1- Chloro-3-methoxy-2-propanol (25.0 g, 0.2 mol) and stirring was continued for 24 h. The reaction solution was cooled to room temperature, filtered, and the filtrate was evaporated to ethyl ether. The crude product was diluted with methylene chloride (250 mL) and washed with aqueous sodium hydroxide (5 wt%, 150 mL×2). The organic phase was dried over anhydrous MgSO~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Mass spectrum of the obtained product And the nuclear magnetic resonance H spectrum data is as follows:

LC-MS (ESI, pos.) m/z: 250 [M+Na] ⁺

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 8.21-8.19 (m, 2H), 7.01-6.98 (m, 2H), 4.24-4.18 (m, 1H), 4.16-4.09 (m, 2H), 3.62-3.55 (m, 2H), 3.43 (s, 3H), 2.74-2.73 (d, 1H).

Step 2: Synthesis of the compound 1-(4-aminophenoxy)-3-methoxypropan-2-ol

1-(4-Nitrophenoxy)-3-methoxypropan-2-ol (27 g, 118.9 mmol), 5% palladium on carbon (25.2 g, 11.9 mmol), ammonium formate (44.9) were sequentially added to a one-neck flask. After a mixture of g, 713.4 mmol) and tetrahydrofuran (100 mL) at room temperature for 5 minutes, the reaction was transferred to a 60 ° C oil bath for 2 h. The reaction was filtered, and the filter cake was washed with THF (100 mL), and the filtrate was washed with saturated aqueous sodium hydrogen carbonate (100 mL×1). After separation, the aqueous phase was extracted with dichloromethane (100 mL×3). After washing with saturated brine (100 ml × 2), the aqueous phase was extracted with dichloromethane (100 mL × 1), and the organic phase was concentrated and dried over anhydrous magnesium sulfate. Liquid (22.7 g, 99%). The mass spectrum of the obtained product and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.) m/z: 198 [M+H] ⁺

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 6.79-6.76 (m, 2H), 6.66-6.64 (m, 2H), 4.17-4.12 (m, 1H), 3.99-3.92 (m, 2H), 3.60-3.52 (m, 2H), 3.42 (s, 3H).

Step 3: Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-methoxypropan-2-ol

1-(4-Aminophenoxy)-3-methoxypropan-2-ol (22.0 g, 111.7 mmol) and methanol (200 mL) were sequentially added to a one-neck flask. BOC anhydride (37.4 g, 171.3 mmol) was diluted with methanol (30 mL) and then added dropwise, and the mixture was stirred at room temperature for 3 h. The mixture was concentrated slightly and then added dropwise to n-hexane (400 mL). After stirring for 10 min, then filtered, filtered and washed with n-hexane (100 mL). The collected solid was dried in vacuo at 40 ° C for 2 h to give an off-white solid (30 g, 87. ). The mass spectrum of the obtained product and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.) m/z: 320 [M+Na] ⁺

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.28-7.27 (m, 2H), 6.88-6.85 (m, 2H), 6.41 (s, 1H), 4.20-4.14 (m, 1H), 4.04- 3.97 (m, 2H), 3.61-3.53 (m, 2H), 3.43 (s, 3H), 2.60-2.59 (d, 1H), 1.53 (s, 9H).

Step 4: Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-methoxypropan-2-yl methacrylate

1-(4-tert-Butoxycarbonylaminophenoxy)-3-methoxypropan-2-ol (15.0 g, 50.5 mmol), triethylamine (10.1 g, 100.0 mmol), 4 were sequentially added to a one-neck flask. Dimethylaminopyridine (1.2 g, 10.0 mmol) and tetrahydrofuran (150 mL) were dissolved. Then, methacryloyl chloride (10.5 g, 100.9 mmol) was slowly added dropwise thereto, and stirred at 0 ° C for 1 h, then transferred to room temperature. Stirring was continued for 24 h. The reaction was quenched by the addition of 50% aqueous sodium bicarbonate (10 mL), and the mixture was stirred for 10 min. (v/v) = 5/1) gave a colorless transparent viscous liquid (17 g, 92.4%). The mass spectrum of the obtained product and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.ion) m / z: 388 [M + Na] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.28-7.26 (m, 2H), 6.87-6.85 (m, 2H), 6.46 (s, 1H), 6.16 (s, 1H), 5.60 (s, 1H), 5.37-5.32 (m, 1H), 4.17-4.11 (m, 2H), 3.71-3.70 (d, 2H), 3.41 (s, 3H), 1.96 (s, 3H), 1.52 (s, 9H) .

Step 5: Synthesis of 1-(4-Aminophenoxy)-3-methoxypropan-2-ylmethacrylate as a compound

To a single-necked flask was added 1-(4-tert-butoxycarbonylaminophenoxy)-3-methoxypropan-2-yl methacrylate (17.0 g, 46.6 mmol) and dichloromethane (100 mL). After fully dissolved, trifluoroacetic acid (70 mL) was added and stirred at room temperature for 15 min. After completion of the reaction, the mixture was neutralized with aq. sodium hydroxide, and the mixture was separated, and the aqueous phase was extracted with dichloromethane (50mL×1). The organic phase was dried over anhydrous magnesium sulfate for 2h, filtered and evaporated to remove solvent to give a pale red viscous liquid. (12.5 g, 98%). The mass spectral data of the obtained product is as follows:

LC-MS (ESI, pos.ion) m / z: 266 [M + H] +.

Step 6: Synthesis of the compound 1-(4-((4-hydroxyphenyl)diazenyl)phenoxy)-3-methoxypropan-2-yl methacrylate

1-(4-Aminophenoxy)-3-methoxypropan-2-yl methacrylate (3.00 g, 11.30 mmol) and potassium bromide (1.35 g, 11.30 mmol) were sequentially added to a three-necked flask. a mixed solution of concentrated hydrochloric acid (5.70g, 56.50mmol) and acetone/water (v/v, 1/1) (20mL), the mixture is stirred in a low temperature bath of -5 °C, when the internal temperature reaches below 0 °C, A solution of sodium nitrite (0.93 g, 13.60 mmol) dissolved in water (20 mL) was slowly added dropwise to the above reaction mixture, and stirring was continued for 0.5 h. A solution of phenol (1.09 g, 11.30 mmol), sodium hydroxide (1.11 g, 28.30 mmol), sodium carbonate (1.50 g, 14.10 mmol) dissolved in water (20 mL) was added dropwise to the above diazonium salt solution, and the dropping process was carried out. Keep the solution temperature no higher than 5 °C. Stirring was continued overnight, and the mixture was poured into dichloromethane (100 mL). EtOAc (EtOAc m. , 53.1%). The mass spectrum of the obtained product and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.ion) m / z: 371 [M + H] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.88-7.83 (m, 4H), 7.04-7.02 (m, 2H), 6.96-6.94 (m, 2H), 6.19 (s, 1H), 5.63 ( s, 1H), 5.44-5.39 (m, 1H), 4.29-4.28 (d, 2H), 3.75-.374 (d, 2H), 3.44 (s, 3H), 1.98 (s, 3H).

Example 2

Compound 1-(4-((4-hydroxyphenyl)diazenyl)phenoxy)-3-methoxyprop-2-yl acrylate

Step 1: Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-methoxyprop-2-yl acrylate

1-(4-tert-Butoxycarbonylaminophenoxy)-3-methoxypropan-2-ol (8.00 g, 26.94 mmol) and triethylamine (5.45 g, 53.96 mmol) were sequentially added to a one-neck flask. After 4-dimethylaminopyridine (0.65 g, 2.50 mmol) and tetrahydrofuran (150 mL) were dissolved, acryloyl chloride (4.80 g, 46.12 mmol) was slowly added dropwise thereto, stirred at 0 ° C for 1 h, then transferred to room temperature and continued. Stir for 24 h. The reaction was quenched by the addition of 50% aqueous sodium hydrogen carbonate (10 mL), and the mixture was stirred for 10 min, then filtered, and then filtered and evaporated to EtOAc (EtOAc) ), a pale red transparent viscous liquid (8.05 g, 81.9%) was obtained. The mass spectrum of the obtained product and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.ion) m / z: 374 [M + Na] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.28-7.26 (m, 2H), 6.88-6.86 (m, 2H), 6.49-6.45 (d, 1H), 6.22-6.15 (m, 1H), 5.89-5.86 (d, 1H), 5.41-5.36 (m, 1H), 4.19-4.13 (m, 2H), 3.71-3.70 (d, 2H), 3.41 (s, 3H), 1.52 (s, 9H).

Step 2: Synthesis of the compound 1-(4-aminophenoxy)-3-methoxyprop-2-yl acrylate

1-(4-tert-Butoxycarbonylaminophenoxy)-3-methoxyprop-2-yl acrylate (8.0 g, 31.87 mmol) and dichloromethane (100 mL) were sequentially added to a single-necked flask to dissolve well. Trifluoroacetic acid (70 mL) was added and stirred at room temperature for 15 min. After completion of the reaction, the mixture was neutralized with aq. sodium hydroxide, and the mixture was separated, and the aqueous phase was extracted with dichloromethane (50mL×1). The organic phase was dried over anhydrous magnesium sulfate for 2h, filtered and evaporated to remove solvent to give a pale red viscous liquid. (4.60 g, 80%). The mass spectrum and nuclear magnetic data of the obtained product are as follows:

LC-MS (ESI, pos.ion) m / z: 252 [M + H] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 6.79-6.77 (m, 2H), 6.65-6.63 (m, 2H), 6.49-6.45 (d, 1H), 6.23-6.16 (m, 1H), 5.88-5.86 (d, 1H), 5.39-5.34 (m, 1H), 4.13-4.11 (m, 2H), 3.71-3.70 (d, 2H), 3.41 (s, 3H).

Step 3: Synthesis of the compound 1-(4-((4-hydroxyphenyl)diazenyl)phenoxy)-3-methoxyprop-2-yl acrylate

1-(4-Aminophenoxy)-3-methoxypropan-2-yl acrylate (1.50 g, 5.90 mmol) and potassium bromide (0.70 g, 5.90 mmol) concentrated hydrochloric acid were added to a three-necked flask. 2.99g, 29.50mmol) and acetone/water (v/v, 1/1) The mixed solution (20 mL), the mixture was stirred in a -5 ° C low temperature bath, when the internal temperature reached below 0 ° C, sodium nitrite (0.48 g, 7.80 mmol) was dissolved in water (20 mL), slowly added dropwise In the reaction mixture, stirring was continued for 0.5 h. Phenol (0.55 g, 5.90 mmol), sodium hydroxide (0.59 g, 14.75 mmol), anhydrous sodium carbonate (0.77 g, 7.34 mmol) were dissolved in water (20 mL) and added dropwise to the above diazonium salt solution. The addition process keeps the solution temperature not higher than 5 °C. Stirring was continued overnight, and the mixture was poured into dichloromethane (100 mL). EtOAc (EtOAc m. , 73.5%). The mass spectrum of the obtained product and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.ion) m / z: 357 [M + H] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.89-7.83 (m, 4H), 7.05-7.02 (m, 2H), 6.96-6.94 (m, 2H), 6.52-6.47 (d, 1H), 6.24-6.17 (m, 1H), 5.91-5.89 (d, 1H), 5.46-5.43 (m, 1H), 4.29-4.28 (m, 2H), 3.76-3.74 (d, 2H), 3.44 (s, 3H) ).

Example 3

1-(4-((2,4-dihydroxyphenyl)diazenyl)phenoxy)-3-methoxyprop-2-yl acrylate

The remaining steps were the same as in Example 1, except that in the step (6), 1-(4-aminophenoxy)-3-methoxypropan-2-yl methacrylate was sequentially added to a three-necked flask. a mixed solution of (3.00 g, 11.30 mmol), potassium bromide (1.35 g, 11.30 mmol) concentrated hydrochloric acid (5.70 g, 56.50 mmol) and acetone/water (v/v, 1/1) (20 mL) Stirring in a -5 ° C low temperature bath. When the internal temperature reached below 0 ° C, sodium nitrite (0.93 g, 13.60 mmol) was dissolved in water (20 mL), slowly added dropwise to the above reaction mixture, and stirring was continued for 0.5 h. Resorcinol (1.23 g, 11.30 mmol), sodium hydroxide (1.11 g, 28.30 mmol), sodium carbonate (1.50 g, 14.10 mmol) were dissolved in water (20 mL) and added dropwise to the above diazonium salt solution. The dropping process keeps the solution temperature not higher than 5 °C. Stirring was continued overnight, the mixture was poured into dichloromethane (100 mL). EtOAc (EtOAc m. 53.8%). The mass spectrum of the obtained product and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.) m/z: 387 [M+H] ⁺

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.80-7.73 (m, 3H), 7.04-7.02 (m, 2H), 6.56-6.53 (d, 1H), 6.44-6.43 (s, 1H), 6.18 (s, 1H), 5.63 (s, 1H), 5.43-5.38 (m, 1H), 4.29-4.27 (d, 2H), 3.75-3.73 (d, 2H), 3.44 (s, 3H), 1.98 ( s, 3H).

Example 4

1-(4-((2,4-dihydroxyphenyl)diazenyl)phenoxy)-3-methoxyprop-2-yl acrylate

The remaining steps were the same as in Example 2 except that in the step (3), 1-(4-aminophenoxy)-3-methoxyprop-2-yl acrylate (1.00) was sequentially added to a three-necked flask. a mixed solution of g, 3.90 mmol), potassium bromide (0.47 g, 3.90 mmol), concentrated hydrochloric acid (2.00 g, 19.50 mmol) and acetone/water (v/v, 1/1) (20 mL) The mixture was stirred in a low temperature bath at 5 ° C. When the internal temperature reached below 0 ° C, sodium nitrite (0.32 g, 4.68 mmol) was dissolved in water (20 mL), and slowly added dropwise to the above reaction mixture, and stirring was continued for 0.5 h. Resorcinol (0.73 g, 3.90 mmol), sodium hydroxide (0.39 g, 9.75 mmol), anhydrous sodium carbonate (0.51 g, 4.87 mmol) were dissolved in water (20 mL) and added dropwise to the above diazonium salt The solution, the dropping process keeps the solution temperature not higher than 5 °C. Stirring was continued overnight, the mixture was poured into dichloromethane (100 mL). EtOAc (EtOAc m. (1.15g, 77.7%). The mass spectrum of the obtained product and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.ion) m / z: 373 [M + H] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.79-7.71 (m, 3H), 7.03-7.01 (m, 2H), 6.55-6.53 (t, 1H), 6.52-6.48 (d, 1H), 6.43-6.42(d,1H), 6.24-6.17(m,1H),5.93-5.90(d,1H),5.47-5.42(m,1H), 4.30-4.25(m,2H),3.76-3.75(d , 2H), 3.45 (s, 3H).

Example 5

1-(4-((4-Hydroxy-2-methoxyphenyl)diazenyl)phenoxy)-3-methoxypropan-2-yl methacrylate and 1-(4(( 2-hydroxy-4-methoxyphenyl)diazenol)phenoxy)-3-methoxypropan-2-yl methacrylate

The remaining steps were the same as in Example 1, except that in the step (6), 1-(4-aminophenoxy)-3-methoxypropan-2-yl methacrylate was sequentially added to a three-necked flask. (2.00 g, 7.50 mmol), a mixed solution of potassium bromide (0.89 g, 7.50 mmol) concentrated hydrochloric acid (3.80 g, 37.7 mmol) and acetone/water (v/v, 1/1) (20 mL), Stirring in a -5 ° C low temperature bath. When the internal temperature reached below 0 ° C, sodium nitrite (0.62 g, 9.00 mmol) was dissolved in water (20 mL), and slowly added dropwise to the above reaction mixture, and stirring was continued for 0.5 h. m-Methoxyphenol (0.93 g, 7.5 mmol), sodium hydroxide (0.75 g, 18.70 mmol), sodium carbonate (0.99 g, 9.40 mmol) were dissolved in water (20 mL) and added dropwise to the above diazonium salt solution The dropping process keeps the solution temperature not higher than 5 °C. Stirring was continued overnight, the mixture was poured into dichloromethane (100 mL). EtOAc (EtOAc m. , 17%) and a red viscous liquid (0.21 g, 7.7%), which was identified as a compound (11) by mass spectrometry and nuclear magnetic identification. The red viscous liquid was identified as a compound after mass spectrometry and nuclear magnetic identification. ). The mass spectrum of the compound (11) and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.ion) m / z: 401 [M + H] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.81-7.76 (m, 3H), 7.05-7.03 (m, 2H), 6.64-6.61 (m, 1H), 6.52-6.49 (m, 1H), 6.18(s,1H), 5.63(s,1H),5.43-5.38(m,1H), 4.29-4.28(d,2H),3.88(s,3H),3.74-3.73(d,2H), 3.44( s, 3H), 1.98 (s, 3H).

The mass spectrum of the compound (5) and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, pos.ion) m / z: 401 [M + H] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.87-7.86 (m, 2H), 7.69-7.68 (m, 1H), 7.02-7.01 (m, 2H), 6.58 (s, 1H), 6.48- 6.47 (m, 1H), 6.18 (s, 1H), 5.63 (s, 1H), 5.42-5.39 (m, 1H), 4.28-4.27 (d, 2H), 4.01 (s, 3H), 3.74-3.73 ( d, 2H), 3.43 (s, 3H), 1.98 (s, 3H).

Example 6

1-(4-((4-Hydroxy-2-methylphenyl)diazenyl)phenoxy)-3-methoxypropan-2-yl methacrylate

The remaining steps were the same as in Example 1, except that in the step (6), 1-(4-aminophenoxy)-3-methoxypropan-2-yl methacrylate was sequentially added to a three-necked flask. (2.00 g, 7.50 mmol), a mixed solution of potassium bromide (0.89 g, 7.50 mmol) concentrated hydrochloric acid (3.80 g, 37.70 mmol) and acetone/water (v/v, 1/1) (20 mL), Stirring in a -5 ° C low temperature bath. When the internal temperature reached below 0 ° C, sodium nitrite (0.62 g, 9.00 mmol) was dissolved in water (20 mL), and slowly added dropwise to the above reaction mixture, and stirring was continued for 0.5 h. M-methylphenol (0.82 g, 7.50 mmol), sodium hydroxide (0.75 g, 18.70 mmol), sodium carbonate (0.99 g, 9.40 mmol) were dissolved in water (20 mL) and added dropwise to the above diazonium salt solution. The dropping process keeps the solution temperature not higher than 5 °C. Stirring was continued overnight, and the mixture was poured into dichloromethane (100 mL). EtOAc (EtOAc/EtOAc (EtOAc) 2.06g, 79.2%). The mass spectrum of the obtained product and the nuclear magnetic resonance H spectrum data are as follows:

LC-MS (ESI, </RTI> ^m .

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.87-7.85 (m, 2H), 7.65-7.62 (d, 1H), 7.03-7.01 (m, 2H), 6.78 (s, 1H), 6.73- 6.70(d,1H), 6.19(s,1H), 5.63(s,1H),5.44-5.39(m,1H), 4.29-4.27(d,2H), 3.76-3.75(d,2H), 3.44( s, 3H), 2.68 (s, 3H), 1.99 (s, 3H).

Example 7

1-ethoxy-3-(4-((4-hydroxyphenyl)diazenyl)phenoxy)propan-2-yl methacrylate

Step 1: Synthesis of compound 1-ethoxy-3-(4-nitrophenoxy)propan-2-ol

4-Nitrophenol (28.0 g, 0.2 mol), potassium carbonate (14.0 g, 0.1 mol) and absolute ethanol (200 mL) were successively added to a three-necked flask, and the mixture was stirred under reflux for 1 hour, and then slowly added dropwise thereto 1- Chloro-3-ethoxy-2-propanol (13.9 g, 0.1 mol) and stirring was continued for 24 h. The reaction solution was cooled to room temperature, filtered, and the filtrate was evaporated to ethyl ether. The crude product was diluted with methylene chloride (200 mL) and washed with aqueous sodium hydroxide (10 wt%, 80 mL×3). The organic phase was dried over anhydrous sodium sulfate for 2 h, filtered and evaporated and evaporated.

LC-MS (ESI, pos.) m/z: 264 [M+Na] ⁺

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 8.24-8.20 (m, 2H), 7.12-6.98 (m, 2H), 4.23-4.14 (m, 1H), 4.13-4.11 (m, 2H), 3.64-3.58 (m, 4H), 2.64 (s, 1H), 1.26-1.19 (t, 3H).

Step 2: Synthesis of the compound 1-(4-aminophenoxy)-3-ethoxypropan-2-ol

1-Ethoxy-3-(4-nitrophenoxy)propan-2-ol (13.3 g, 55.2 mmol), 5% palladium on carbon (11.7 g, 5.5 mmol), ammonium formate were sequentially added to a one-neck flask. (20.9 g, 33.1 mmol) and tetrahydrofuran (50 mL), and the mixture was stirred at 45 ° C for 1 h. The reaction was filtered, and the filter cake was washed with dichloromethane (100 mL). The filtrate was diluted with dichloromethane to 250 mL, and washed with brine (80ml×4). After filtration, the solvent was evaporated <RTI ID=0.0>

LC-MS (ESI, pos.ion) m / z: 212 [M + H] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 6.79-6.77 (m, 2H), 6.67-6.64 (m, 2H), 4.17-4.12 (m, 1H), 4.00-3.93 (m, 2H), 3.64-3.55 (m, 4H), 3.47 (s, 2H), 2.65 (s, 1H), 1.30-1.22 (t, 3H).

Step 3: Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-ethoxypropan-2-ol

1-(4-Aminophenoxy)-3-ethoxypropan-2-ol (10.0 g, 47.4 mmol), BOC anhydride (12.5 g, 56.9 mmol) and methanol (50 mL) were sequentially added to a single-neck flask. The mixture was stirred at room temperature for 1 h. The reaction was added to hexane (300 mL). EtOAc (EtOAc)EtOAc.

LC-MS (ESI, pos.ion) m / z: 334 [M + Na] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.28-7.27 (m, 2H), 6.89-6.86 (m, 2H), 6.37 (s, 1H), 4.18-4.14 (m, 1H), 4.04- 3.97 (m, 2H), 3.65-3.56 (m, 4H), 2.58-2.56 (d, 1H), 1.53 (s, 9H), 1.26-1.22 (t, 3H).

Step 4: Synthesis of the compound 1-(4-tert-butoxycarbonylaminophenoxy)-3-ethoxypropan-2-yl methacrylate

1-(4-tert-Butoxycarbonylaminophenoxy)-3-ethoxypropan-2-ol (11.0 g, 33.2 mmol) and diisopropylethylamine (14.2 g, 108.5) were sequentially added to a one-neck flask. After lysing, 4-dimethylaminopyridine (0.86 g, 7.0 mmol) and tetrahydrofuran (70 mL) were dissolved, methacryloyl chloride (18.4 g, 176.9 mmol) was slowly added dropwise and stirring was continued for 24 h. The reaction mixture was filtered and evaporated to dryness crystals eluted eluted eluted eluted

LC-MS (ESI, pos.ion) m / z: 402 [M + Na] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.28-7.26 (m, 2H), 6.89-6.86 (m, 2H), 6.37 (s, 1H), 6.16 (s, 1H), 5.60 (s, 1H), 5.37-5.31 (m, 1H), 4.18-4.12 (m, 2H), 3.74-3.73 (d, 2H), 3.60-3.53 (m, 2H), 1.97 (s, 3H), 1.53 (s, 9H), 1.30-1.19 (t, 3H).

Step 5: Synthesis of the compound 1-(4-aminophenoxy)-3-ethoxypropan-2-yl methacrylate

1-(4-tert-Butoxycarbonylaminophenoxy)-3-ethoxypropan-2-ylmethacrylic acid (9.0 g, 23.7 mmol), trifluoroacetic acid/dichloromethane was added to a single-necked flask. The solution (v/v, 3/4, 35 mL) was fully dissolved and stirred at room temperature for 15 min. The reaction mixture was diluted with methylene chloride (EtOAc) (EtOAc m. v/v) = 1:1) to give a brown viscous liquid (5.4 g, 75%).

LC-MS (ESI, pos.) m/z: 280 [M+H] ⁺

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 6.79-6.76 (m, 2H), 6.66-6.63 (m, 2H), 6.16 (s, 1H), 5.60 (s, 1H), 5.35-5.30 ( m, 1H), 4.17-4.09 (m, 2H), 3.74 - 3.72 (d, 2H), 3.62-3.51 (m, 2H), 1.97 (s, 3H), 1.22-1.19 (t, 3H).

Step 6: Synthesis of compound 1-ethoxy-3-(4-((4-hydroxyphenyl)diazenyl)phenoxy)propan-2-yl methacrylate

To the three-necked flask, 1-(4-aminophenoxy)-3-ethoxypropan-2-yl methacrylate (0.84 g, 3.00 mmol) obtained in the step (5) and potassium bromide (0.41) were sequentially added. g, 3.40 mmol) a mixed solution of concentrated hydrochloric acid (1.12 g, 11.00 mmol) and acetone/water (v/v, 1/1) (20 mL), the mixture was stirred in a low temperature bath at -5 ° C, when the internal temperature reached 0 Sodium nitrite (0.23 g, 3.30 mmol) was dissolved in water (10 mL), slowly added dropwise to the above reaction mixture, and stirring was continued for 0.5 h. Phenol (0.32 g, 3.30 mmol) and sodium hydroxide (0.13 g, 3.30 mmol) were dissolved in water (15 mL), and added dropwise to the above diazonium salt solution, and the dropwise addition process kept the solution temperature not higher than 5 °C. After the stirring was continued for 0.5 h, the reaction was filtered, and then filtered and washed with water (100mL), and the solid was collected by column chromatography (hexane/EtOAc (v/v) = 5/1) to give an orange viscous liquid (0.40 g, 34%).

LC-MS (ESI, pos.ion) m / z: 407 [M + Na] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.88-7.83 (m, 4H), 7.05-7.02 (d, 2H), 6.96-6.94 (d, 2H), 6.18 (s, 1H), 5.62 ( s, 1H), 5.43-5.38 (m, 1H), 4.31-4.18 (m, 2H), 3.78-3.77 (m, 2H), 3.63-3.56 (m, 2H), 1.98 (s, 3H), 1.25- 1.21 (t, 3H).

Example 8

1-(4-((2,4-dihydroxyphenyl)diazenyl)phenoxy)-3-ethoxypropan-2-yl methacrylate

The remaining steps were the same as in Example 7, except that in the step (6), 1-(4-aminophenoxy)-3-ethoxypropan-2-yl methacrylate was sequentially added to a three-necked flask. (0.84g, 3.00mmol), potassium bromide (0.41g, 3.40mmol) concentrated hydrochloric acid (1.12g, 11.00mmol) and acetone / water (v / v, 1 / 1) mixed solution (20mL), the mixture in Stirring in a -5 ° C low temperature bath. When the internal temperature reached below 0 ° C, sodium nitrite (0.23 g, 3.30 mmol) was dissolved in water (10 mL), slowly added dropwise to the above reaction mixture, and stirring was continued for 0.5 h. m-Diphenol (0.36g, 3.30mmol), sodium hydroxide (0.26g, 6.60mmol) was dissolved in water (15mL), and added dropwise to the above diazonium salt solution, the dropping process kept the solution temperature not higher than 5 °C . After the stirring was continued for 0.5 h, the reaction was filtered and EtOAcjjjjjjjjjjjjjjjjjjjjjjjjjj %).

LC-MS (ESI, pos.ion) m / z: 423 [M + Na] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.77-7.75 (d, 2H), 7.71-7.70 (d, 1H), 7.02-7.00 (d, 2H), 6.54-6.52 (t, 1H), 6.42-6.42(d,1H), 6.19(s,1H), 5.64(s,1H),5.42-5.39(m,1H), 4.30-4.26(m,2H),3.79-3.78(m,2H), 3.64-3.57 (m, 2H), 1.99 (s, 3H), 1.25-1.23 (t, 3H).

Example 9

1-ethoxy-3-(4-((4-hydroxy-2-methoxyphenyl)diazenyl)phenoxy)propan-2-yl methacrylate

The remaining steps were the same as in Example 7, except that in the step (6), 1-(4-aminophenoxy)-3-ethoxypropan-2-ylmethacrylate was sequentially added to a three-necked flask ( 0.84 g, 3.0 mmol), a mixed solution of potassium bromide (0.41 g, 3.40 mmol) concentrated hydrochloric acid (1.20 g, 11.80 mmol) and acetone/water (v/v, 1/1) (20 mL), 5 ° C low temperature The mixture was stirred in a bath. When the internal temperature reached below 0 ° C, sodium nitrite (0.23 g, 3.30 mmol) was dissolved in water (10 mL), slowly added dropwise to the above reaction mixture, and stirring was continued for 0.5 h. M-methoxyphenol (0.41 g, 3.30 mmol), sodium hydroxide (0.13 g, 3.3 mmol) was dissolved in water (15 mL), and added dropwise to the above diazonium salt solution. The dropping process kept the solution temperature not higher than 5 ° C. After the stirring was continued for 0.5 h, the reaction was filtered and EtOAcjjjjjjjjjjjjjjjjjjjjj %).

LC-MS (ESI, pos.ion) m / z: 415 [M + H] +;

_{^{1 H NMR (400MHz, CDCl 3}} ) δ (ppm): 7.86-7.84 (d, 2H), 7.67-7.65 (d, 1H), 7.10-6.99 (d, 2H), 6.57 (s, 1H), 6.48- 6.46(t,1H), 6.17(s,1H), 5.62(s,1H),5.41-5.37(m,1H), 4.30-4.27(m,2H),3.98(s,3H),3.77-3.76( d, 2H), 3.62-3.53 (m, 2H), 1.98 (s, 3H), 1.24-1.20 (t, 3H).

Comparative Example 1 Preparation of Polymer A0

2-Phenylethyl acrylate (0.3500 g), 2-phenylethyl methacrylate (0.2500 g), ethoxyethyl methacrylate (0.3500 g), 1,4-butanediol II Acrylate (0.0350g), 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-propenyl)phenol (0.0100g) and bis(4-tert-butylcyclohexyl) The oxidized dicarbonate (0.0100 g) (with no azo compound added) was uniformly mixed, and then transferred to a mold consisting of two layers of glass and a 0.4 mm thick polytetrafluoroethylene sheet, and the mold was placed at 60 ° C. The reaction was carried out in an oven for 3 hours, and the oven was elevated to 100 ° C and maintained for 3 hours to obtain a transparent and elastic polymer. The obtained material was ultrasonically washed in absolute ethanol and vacuum dried at 60 ° C for 24 hours.

Example 10 Preparation of Polymer A1

2-Phenylethyl acrylate (0.3500 g), 2-phenylethyl methacrylate (0.2500 g), ethoxyethyl methacrylate (0.3500 g), 1,4-butanediol II Acrylate (0.0350g), 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-propenyl)phenol (0.0100g), bis(4-tert-butylcyclohexyl) The oxidized dicarbonate (0.0200 g) and the azo compound (0.0010 g) prepared in Example 1 were uniformly mixed, and then transferred to a mold composed of two layers of glass and a 0.4 mm thick polytetrafluoroethylene sheet, and then The mold was placed in an oven at 60 ° C for 3 hours, and the oven was elevated to 100 ° C and maintained for 3 hours to obtain a transparent and elastic polymer. The obtained material was ultrasonically cleaned in absolute ethanol and vacuum dried at 60 ° C for 24 hours. That is, the polymer A1 is obtained.

Examples 11 to 18 prepared polymers A2 to A9

The rest of the procedure was the same as in Example 10 except that the azo compounds prepared in Examples 2 to 9 were used in place of the azo compounds prepared in Example 1, respectively, to obtain polymers A2 to A9.

Example 19 Preparation of Polymer A10

2-Phenylethyl acrylate (0.3500 g), 2-phenylethyl methacrylate (0.2500 g), ethoxyethyl methacrylate (0.3500 g), 1,4-butanediol II Acrylate (0.0350g), 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2- Propylene-based phenol (0.0100 g), bis(4-tert-butylcyclohexyl)peroxydicarbonate (0.0100 g) and the azo compound prepared in Example 3 (0.00150 g) were uniformly mixed and then transferred to a two-layer glass. And a mold consisting of a 0.4 mm thick polytetrafluoroethylene sheet, and then the mold was placed in an oven at 60 ° C for 3 hours, and the oven was raised to 100 ° C for 3 hours to obtain a transparent and elastic polymerization. The material obtained was ultrasonically washed in absolute ethanol and dried under vacuum at 60 ° C for 24 hours.

Comparative Example 2 Preparation of Polymer A11

2-Phenylethyl acrylate (0.3500 g), 2-phenylethyl methacrylate (0.2500 g), ethoxyethyl methacrylate (0.3500 g), 1,4-butanediol II Acrylate (0.0350g), 2-(2H-benzotriazol-2-yl)-4-methyl-6-(2-propenyl)phenol (0.0100g), bis(4-tert-butylcyclohexyl) The oxidized dicarbonate (0.0100g) and the traditional dye 4-hydroxy azobenzene (0.0010g) are uniformly mixed and then transferred to a mold consisting of two layers of glass and a 0.4mm thick Teflon sheet. The mold was placed in an oven at 60 ° C for 3 hours, and the oven was elevated to 100 ° C and maintained for 3 hours to obtain a transparent and elastic polymer. The obtained material was ultrasonically cleaned in absolute ethanol and vacuum dried at 60 ° C for 24 hours. .

Example 20 Spectral Transmittance Measurement

(1) Test method: The spectral transmittance of the material in the range of 200 nm to 800 nm light wave was measured by an Agilent Cary 60 ultraviolet-visible spectrophotometer at room temperature.

(2) Test results:

The spectral transmittances of the respective polymers prepared in Examples 10 to 19 and Comparative Examples 1 and 2 are shown in Table 1. Figures 1-3 show a comparison of the spectral transmittances of the polymers prepared in some of the examples and the polymers prepared in the comparative examples. As can be seen from the table and the accompanying drawings, the comparative test material A0 to which the yellow dye (azo compound) of the present invention is not added has a strong transmittance at 400 nm and a transmittance at 450 nm (blue light region). Above 90%, there is almost no absorption of blue light. The addition of the polymers A1 to A10 of the yellow dye of the present invention can significantly reduce the spectral transmission of wavelengths between 400 and 500 nm, and has good absorption of blue light in the range, and the spectral transmittance in the visible range. The maximum values were all above 91%, indicating that the polymer added to the yellow dye of the present invention maintained good transparency. Moreover, the polymer synthesized by the present invention also has good blue light absorption properties and spectral transmittance as compared with Comparative Example 2 using a conventional dye.

Table 1

Example	polymer	450nm transmittance (%)	Maximum transmittance (%)
Comparative example 1	A0	90.16386	92.15835
Example 10	A1	59.01423	91.14392

Example	polymer	450nm transmittance (%)	Maximum transmittance (%)
Example 11	A2	58.97997	91.63613
Example 12	A3	24.23858	92.48477
Example 13	A4	5.437931	91.89379
Example 14	A5	15.10579	91.09235
Example 15	A6	50.16385	91.43137
Example 16	A7	63.43479	91.82819
Example 17	A8	21.50296	91.91238
Example 18	A9	33.92863	91.37845
Example 19	A10	5.781409	91.36183

Example 21 Polymer Material Extraction Experiment and Test Results

(1) Extraction experiment method:

The polymers A1, A2, A4, A6, A9, and A11 prepared in the previous examples were each cut into a sheet having a width of about 15 × 10 mm, and placed in a Soxhlet extractor and rinsed with anhydrous ethanol under reflux. The frequency at which the extract flushed the extraction cannula was 2 times/hour. After 24 hours of extraction, the sample was taken out, and dried at 60 ° C for 24 hours, and then the spectral transmittance of the sample was measured, and the loss rate of absorption efficiency of each sample at 450 nm before and after the extraction was calculated.

(2) Test results:

The spectral absorption data and the 450 nm absorption loss rate of each sample before and after the extraction of the polymers A1, A2, A4, A6, A9, and A11 are shown in Table 2. Figure 4 is a comparison of spectral transmittance before and after extraction of A4 and A11. The comparison shows that after extraction, the absorption efficiency of blue light by the polymer A11 added with the traditional dye 4-hydroxyazobenzene is significantly reduced (the absorption efficiency is reduced by 43.8%), indicating that the traditional dye added in the polymer is less stable, so When artificial crystals are prepared therefrom, the risk of azo compounds in the polymer entering the human eye is greater. The absorption efficiency of blue light added to the polymer of the dye of the present invention does not change significantly before and after the extraction (absorption loss rate is less than 3%), indicating that the yellow dye of the present invention is formed by having a polymerizable double bond. The polymer participates in the reaction, and the dye and the material matrix are covalently bonded to each other, which effectively improves the biocompatibility of the yellow crystal material and the stability of absorption of blue light. Referring to Fig. 5, the absorption loss rate of each polymer synthesized by the present invention before and after extraction is not higher than 3%, and the absorption loss rate of the conventional dye after extraction is as high as 45%. The other polymers synthesized by the present invention were tested and the test results were similar to those shown in Table 2.

Table 2

In the description of the present specification, the description of the terms "one embodiment", "another embodiment", "an example" or the like means that a specific feature, structure, material or characteristic described in connection with the embodiment or example is included in the present invention. At least one embodiment or example. In the present specification, the schematic representation of the above terms is not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in a suitable manner in any one or more embodiments or examples. In addition, various embodiments or examples described in the specification, as well as features of various embodiments or examples, may be combined and combined.

While the embodiments and the embodiments of the present invention have been shown and described, it is understood that the foregoing embodiments and examples are illustrative and not restrictive Variations, modifications, substitutions and variations of the above-described embodiments and embodiments may be made within the scope of the invention.

Claims (17)

1. An azo compound characterized in that the azo compound is a compound represented by the formula (Ia) or a stereoisomer or tautomer of the compound represented by the formula (Ia):

   

   among them,

   R ¹ is hydrogen or alkyl; R ² is alkyl;

   X is O, NH or NR ⁵ ; Y is O, S, NH or NR ⁵ ; wherein each R ^{5 is} independently C _1-10 alkyl;

   W is a single bond, an alkylene group or a heteroalkylene group; W is optionally 1, 2, 3, 4 or 5 fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, oxygen Substituted (=O), C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylthio or C _1-6 alkylamino;

   R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR ^a R ^b , -C(=O)R ^c , -S(=O ₂ R ^c , -C(=O)NR ^a R ^b , -S(=O) ₂ NR ^a R ^b , C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkane , halogenated C _1-6 alkoxy, C _1-6 alkoxy C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-12 aryl, C _{6- 12} aryl C _1-6 alkyl group, C _6-12 aryloxy, C _6-12 aryloxy C _1-6 alkyl or C _6-12 aryl C _1-6 alkoxy group; and

   Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-6 alkyl group;

   n is 0, 1, 2, 3 or 4;

   m is 0, 1, 2, 3, 4 or 5.
2. The azo compound according to claim 1, wherein in the azo compound represented by the formula (Ia):

   R ¹ is hydrogen or C _1-4 alkyl; R ² is C _1-6 alkyl;

   X is O or NH; Y is O or S; W is a single bond, C _1-12 alkylene or C _1-12 heteroalkylene; W is optionally 1, 2, 3, 4 or 5 fluorine , chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, oxo (=O), C _1-6 alkyl, C _1-6 alkoxy, C _1-6 alkylthio or C Substituted with _1-6 alkylamino group;

   R ³ and R ⁴ are each independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR ^a R ^b , -C(=O)R ^c , -S(=O ₂ R ^c , -C(=O)NR ^a R ^b , -S(=O) ₂ NR ^a R ^b , C _1-6 alkyl, C _1-6 alkoxy, halogenated C _1-6 alkane , halogenated C _1-6 alkoxy, C _1-6 alkoxy C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-12 aryl, C _{6- 12} aryl C _1-6 alkyl group, C _6-12 aryloxy, C _6-12 aryloxy C _1-6 alkyl or C _6-12 aryl C _1-6 alkoxy group; and

   Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-6 alkyl group;

   n is 0, 1, 2, 3 or 4;

   m is 0, 1, 2, 3, 4 or 5.
3. The azo compound according to claim 1, wherein the azo compound is a compound represented by the formula (I) or a stereoisomer or tautomer of the compound represented by the formula (I):

   

   among them,

   R ¹ is H or an alkyl group;

   R ² is an alkyl group;

   R ^{3 is} independently hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, aldehyde, nitro, cyano, -NR ^a R ^b , -C(=O)R ^c , -S(=O) ₂ R ^c , -C(=O)NR ^a R ^b , -S(=O) ₂ NR ^a R ^b , alkyl, alkoxy, halo C _1-6 alkyl, halo C _1-6 alkoxy , C _1-6 alkoxy C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _6-12 aryl, C _6-12 aryl C _1-6 alkyl, C _6-12 aryloxy, C _6-12 aryloxy C _1-6 alkyl or C _6-12 aryl C _1-6 alkoxy;

   Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _1-6 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-6 alkyl group;

   m is 0, 1, 2, 3, 4 or 5.
4. The azo compound according to any one of claims 1 to 3, wherein the R ¹ is H or a methyl group.
5. The azo compound according to any one of claims 1 to 4, wherein the R ² is a C _1-6 alkyl group.
6. The azo compound according to any one of claims 1 to 5, wherein the R ² is a methyl group, an ethyl group, a n-propyl group, an isopropyl group, an n-butyl group or an isobutyl group.
7. The azo compound according to any one of claims 1 to 6, wherein the R ^{3 is} independently hydrogen, fluorine, chlorine, bromine, iodine, a hydroxyl group, an aldehyde group, a nitro group, a cyano group, or NR ^a R ^b , -C(=O)R ^c , -S(=O) ₂ R ^c , -C(=O)NR ^a R ^b , -S(=O) ₂ NR ^a R ^b , C _{1- 4-} alkyl, C _1-4 alkoxy, halo C _1-4 alkyl, halo C _1-4 alkoxy, C _1-4 alkoxy C _1-4 alkyl, C _2-4 olefin , C _2-4 alkynyl, C _6-10 aryl, C _6-10 aryl C _1-4 alkyl, C _6-10 aryloxy, C _6-10 aryloxy C _1-4 alkyl Or a C _6-10 aryl C _1-4 alkoxy group;

   Each of R ^a , R ^b and R ^{c is} independently hydrogen, hydroxy, C _1-4 alkyl, C _2-4 alkenyl, C _2-4 alkynyl, C _1-4 alkoxy, C _6-10 aryl Or a C _6-10 aryl C _1-4 alkyl group.
8. The azo compound according to any one of claims 1 to 7, wherein each of R ^{3 is} independently hydrogen, fluorine, chlorine, bromine, iodine, cyano, hydroxy, nitro, aldehyde, or NH ₂ , -N(CH ₃ ) ₂ , -C(=O)CH ₃ , -C(=O)OH, -C(=O)OCH ₃ , -CONH ₂ , -CON(CH ₃ ) ₂ , A Base, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutyl Oxyl, trifluoromethyl, trifluoromethoxy, trifluoroethyl, trifluoroethoxy, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, B Oxyethyl, ethoxypropyl, phenyl, phenylmethyl, phenethyl, phenylpropyl, phenoxy, phenoxymethyl, phenoxyethyl, phenylmethoxy or benzene Ethyloxy.
9. The azo compound according to any one of claims 1 to 8, wherein R ¹ is H or a methyl group, R ² is a methyl group or an ethyl group, and m is 1 or 2, R ^{3 is} independently hydroxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, methoxyethyl, trifluoromethyl, Trifluoromethoxy, fluoro, chloro or bromo.
10. The azo compound according to any one of claims 1 to 9, wherein the azo compound is a compound represented by the formula (1) to (20), or a stereoisomer of the compound or Tautomers:

    

    

    
11. A polymer characterized in that the monomer constituting the polymer comprises a bulk monomer and a blue light absorber, and the blue light absorber is the azo compound according to any one of claims 1 to 10.
12. The polymer according to claim 11, wherein the bulk monomer comprises at least one of a (meth) acrylate monomer, a vinyl monomer, and an allyl monomer.
13. The polymer according to claim 11 or 12, wherein the raw material constituting the polymer further comprises at least one of a crosslinking agent, an ultraviolet absorber, and an initiator.
14. An ophthalmic medical device comprising the polymer according to any one of claims 11 to 13.
15. The ocular medical device according to claim 14, wherein the ocular medical device is an intraocular lens, an intraocular lens, a contact lens, a corneal correction, an intracorneal lens, a corneal inlay, a corneal ring, or a glaucoma filter. Optical device.
16. A method of preparing the polymer of any one of claims 11 to 13, comprising:

    Gradging heat treatment or photocuring treatment of the raw material mixture to obtain the polymer,

    Wherein the raw material mixture contains a bulk monomer, a blue light absorber, and optionally at least one selected from the group consisting of a crosslinking agent, an initiator, and an ultraviolet absorber.
17. The method of claim 16 wherein said gradient heating process comprises:

    In the first reaction stage, the temperature of the first reaction stage is 40 to 120 degrees Celsius, and the reaction time is 1 to 48 hours;

    In the second reaction stage, the temperature of the second reaction stage is 40 to 140 degrees Celsius, and the reaction time is 1 to 48 hours.

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