Azaadenine compound, and preparation method therefor and use thereof

Abstract

Provided in the present application are an azaadenine compound, and a preparation method therefor and the use thereof. The azaadenine compound has a structure as represented by formula (I). The azaadenine compound of the present application is applied to a polyimide material without any change to the existing formulation, can maintain the original application performance of a product after the application and improves the stability of the product, with excellent heat resistance.

Description

Aza-adenine compound and preparation method and application thereof TECHNICAL FIELD

[0001] The present application belongs to the field of organic chemistry, and particularly relates to an aza-adenine compound and a preparation method and application thereof. BACKGROUND

[0002] It is known that adenine compounds are useful as therapeutic and / or prophylactic agents for allergic diseases, viral diseases or cancers, etc., and different adenine compounds are reported to be applied in the medical field in CN101679433A, CN1054982A and CN1250548C.

[0003] On the other hand, purine compounds represented by 8-aza-adenine as the main body have been widely used in the manufacture of polyimide compounds, and adenine compounds are reported to be applied in negative photosensitive resin compositions in CN102375336A, CN114467057A and CN112334833A.

[0004] However, such products still need to be further enriched, especially in the application of polyimide compounds, the copper surface bonding force of the products still needs to be further broken through, and low-cost and easily available compounds need to be found, in addition, the heat resistance after the application of the composition needs to be maintained. SUMMARY

[0005] The following is a summary of the subject matter described in detail herein. This summary is not intended to limit the scope of the claims.

[0006] In view of the deficiencies of the prior art, the purpose of the present application is to provide an aza-adenine compound and a preparation method and application thereof.

[0007] To achieve this purpose, the present application adopts the following technical solutions:

[0008] In one aspect, the present application provides an aza-adenine compound, which has the structure shown in formula (I):

[0009] wherein R1 is selected from hydrogen or deuterium, nitro or cyano, and R2 is selected from C1-C20 straight-chain or branched alkyl, C3-C10 cycloalkyl, C6-C12 aryl or C6-C18 aryloxyalkyl.

[0010] In the present application, the aza-adenine compound is applied in polyimide materials without changing the existing use formula, and after application, the original application performance of the product can be maintained, and the stability of the product is improved, and the heat resistance is excellent.

[0011] In the present application, the C1-C20 can be C1, C2, C3, C4, C5, C8, C10, C12, C14, C16, C18, or C20, etc.; the C3-C10 can be C3, C4, C5, C6, C7, C8, C9, or C10; the C6-C12 can be C6, C7, C8, C9, C10, C11, or C12; the C6-C18 can be C6, C7, C8, C9, C10, C11, C12, C14, C16, or C18, etc.

[0012] In one embodiment, R2is selected from any one of methyl, ethyl, butyl, isopropyl, tert-butyl, n-propyl, isopropyl, n-butyl, isobutyl, cyclohexyl, phenyl, benzyl or wherein the wavy line represents the point of attachment of the group.

[0013] Further in one embodiment, the azanucleoside is selected from any one of the following compounds:

[0014] In another aspect, the present application provides a method of preparing an azanucleoside compound as described above, the method comprising the steps of:

[0015] I. Synthesis of non-deuterium labeled product: starting material a is reacted with starting material b to obtain product A, the reaction scheme is as follows:

[0016] In one embodiment, the reaction is carried out in a solvent, preferably any one of or a combination of at least two of dimethylformamide (DMF), dimethylacetamide (DMAc), dimethylsulfoxide (DMSO), or N-methylpyrrolidone (NMP).

[0017] In one embodiment, the reaction is carried out in the presence of an acid binding agent.

[0018] In one embodiment, the acid binding agent is selected from any one of or a combination of at least two of morpholine, piperidine, triethylamine, or 4-dimethylaminopyridine.

[0019] In one embodiment, the molar ratio of starting material a to starting material b is 1.0:1.2-1.0:3.0, for example 1.0:1.2, 1.0:1.5, 1.0:1.8, 1.0:2.0, 1.0:2.3, 1.0:2.5, 1.0:2.8, or 1.0:3.0.

[0020] In one embodiment, the reaction is carried out at room temperature under stirring. Room temperature in the present application means 15-35 °C, such as 15 °C, 18 °C, 20 °C, 25 °C, 28 °C, 30 °C or 35 °C.

[0021] In one embodiment, the reaction time is 4-24 h, such as 4 h, 6 h, 8 h, 10 h, 12 h, 14 h, 16 h, 18 h, 20 h, 22 h or 24 h.

[0022] II. Synthesis of deuterium-labeled product: (1) the starting material a is reacted with deuterium-labeled trifluoro substituted sulfonic acid to obtain product B;

[0023] (2) product B is reacted with starting material b to obtain deuterium-labeled product C, the reaction scheme is as follows:

[0024] In one embodiment, the molar ratio of starting material a to deuterium-labeled trifluoromethanesulfonic acid in step (1) is 1 :5-1 :20, such as 1 :5, 1 :6, 1 :7, 1 :8, 1 :9, 1 :10, 1 :11, 1 :12, 1 :13, 1 :14, 1 :15, 1 :16, 1 :17, 1 :18, 1 :19 or 1 :20.

[0025] In one embodiment, the reaction in step (1) is carried out in a solvent, which is any one or a combination of at least two of tetrahydrofuran, hexahydro pyran, 1,4-dioxane or 4-methyl pyran.

[0026] In one embodiment, the reaction in step (1) is carried out at a temperature of 60-130 °C, such as 60 °C, 70 °C, 80 °C, 90 °C, 100 °C, 110 °C, 120 °C or 130 °C, and a reaction time of 12-48 h, such as 12 h, 15 h, 18 h, 20 h, 24 h, 28 h, 30 h, 33 h, 36 h, 40 h, 44 h or 48 h.

[0027] In one embodiment, the molar ratio of product B to starting material b in step (2) is 1.0:1.2-1.0:3.0, such as 1.0:1.2, 1.0:1.5, 1.0:1.8, 1.0:2.0, 1.0:2.3, 1.0:2.5, 1.0:2.8 or 1.0:3.0.

[0028] In one embodiment, the reaction in step (2) is carried out in a solvent, which is preferably any one or a combination of at least two of dimethylformamide (DMF), dimethylacetamide (DMAc), dimethyl sulfoxide (DMSO) or N-methyl pyrrolidone (NMP).

[0029] In one embodiment, the reaction in step (2) is carried out in the presence of an acid binding agent.

[0030] In one embodiment, the acid binding agent is selected from any one or a combination of at least two of morpholine, piperidine, triethylamine or 4-dimethylaminopyridine.

[0031] In one embodiment, the reaction of step (2) is carried out at room temperature with stirring. Room temperature in the present application refers to 15-35°C, such as 15°C, 18°C, 20°C, 25°C, 28°C, 30°C or 35°C.

[0032] In one embodiment, the reaction time of step (2) is 4-24h, such as 4h, 6h, 8h, 10h, 12h, 14h, 16h, 18h, 20h, 22h or 24h.

[0033] In another aspect, the present application provides use of the azetidine compound as described above in a polyimide material.

[0034] In another aspect, the present application provides a photosensitive composition comprising a polyimide resin, the azetidine compound as described above and an initiator.

[0035] In one embodiment, the content of each component in the photosensitive composition is: 100 parts by mass of the polyimide resin, 1-10 parts by mass (such as 1 part by mass, 2 parts by mass, 3 parts by mass, 4 parts by mass, 5 parts by mass, 7 parts by mass, 9 parts by mass or 10 parts by mass) of the azetidine compound as described above and 0.5-10 parts by mass (such as 0.5 parts by mass, 1 part by mass, 2 parts by mass, 3 parts by mass, 4 parts by mass, 5 parts by mass, 7 parts by mass, 9 parts by mass or 10 parts by mass) of the initiator.

[0036] In one embodiment, the initiator is selected from any one or a combination of at least two of 1-(6-(2-methylbenzoyl)-9-ethylcarbazol-3-yl)-3-cyclopentyl-propan-1-one-acetic acid oxime ester, 1-(4-phenylthiophenyl)-n-octane-1,2-dione-2-benzoic acid oxime ester, 1-(6-(2-methylbenzoyl)-9-ethylcarbazol-3-yl)-ethane-1-one-acetic acid oxime ester, NCI-831, NCI-930, NCI-1919, SPI-02, SPI-03, SPI-04, DFI-091, DFI-020, TR-PBG-314, TR-PBG-331, TR-PBG-365 or TR-PBG-380.

[0037] Compared with the prior art, the present application has the following beneficial effects:

[0038] The azaadenine compound of this application can be used in polyimide materials without changing the existing formulation. After application, it can maintain the original performance of the product and improve the product's stability and heat resistance.

[0039] After reading and understanding the detailed description, other aspects can be understood. Detailed Implementation

[0040] The technical solution of this application will be further described below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely to help understand this application and should not be regarded as specific limitations on this application.

[0041] Preparation Example 1

[0042] 4.5 g of starter 1a (8-azaadenine) and 45 mL of LDM were added to a 100 mL four-necked flask. 4.5 g of triethylamine was added under stirring, followed by dropwise addition of 10.8 g of starter 1b (di-tert-butyl dicarbonate). After the addition was complete, the mixture was stirred at room temperature for 20 h, and the reaction was monitored by TLC until the starter disappeared. The reaction mixture was filtered, and the filter cake was slurried with 5 times its mass of methanol at room temperature for 1 h. The slurry was then filtered again, and the filter cake was dried to obtain 4.3 g of off-white solid (HPLC 99.5%).

[0043] The structure of compound 1 was determined by 1 The H-NMR analysis confirmed the findings, and the characterization results are as follows: 1 H-NMR (d6-DMSO, 500MHz): 8.68 (1H, brs), 8.45 (1H, s), 8.33 (1H, brs), 1.68 (9H, s).

[0044] Preparation Example 2

[0045] 5 g of starting material 1a (8-azaadenine) and 100 g of 1,4-dioxane were added to a 100 mL four-necked flask. Stirring was started, and the system was heated to reflux. 33.4 g of deuterated trifluoromethanesulfonic acid was added dropwise under reflux conditions. After the addition was complete, the reaction was continued under reflux for 10 h. After the reaction was complete, the system was cooled, and solvent was removed under reduced pressure. Saturated sodium carbonate solution was added to the remaining reaction solution to adjust the pH to 10–11. A suitable amount of acetone was added, and the mixture was filtered to remove salt. The mother liquor was concentrated to obtain a crude product. The crude product was slurried with 95% acetone aqueous solution to obtain 4.3 g of a pale yellow solid intermediate 1a (HPLC 99.43%), with a deuteration rate >90%.

[0046] intermediate 1a structure 1 The H-NMR analysis confirmed the findings, and the characterization results are as follows: 1H-NMR(d6-DMSO,500MHz):7.89(1H,brs),6.66(2H,brs).

[0047] 4.5 g of intermediate 1a and 45 mL of LDMF were added to a 100 mL four-necked flask. 4.5 g of triethylamine was added under stirring, followed by dropwise addition of 10.8 g of starting material b (di-tert-butyl dicarbonate). After the addition was complete, stirring was continued at room temperature for 20 h. The reaction was monitored by TLC until the starting material disappeared. The reaction solution was filtered, and the filter cake was slurried with 5 times its mass of methanol at room temperature for 1 h. The mixture was then filtered again, and the filter cake was dried to obtain 3.9 g of a white solid compound 2 (HPLC 99.47%).

[0048] The structure of compound 2 was determined by 1 H-NMR confirmed the findings, and the characterization results are as follows. 1 H-NMR (d6-DMSO, 500MHz): 8.73 (1H, brs), 8.31 (1H, brs), 1.67 (9H, s).

[0049] Furthermore, referring to the method of the embodiments, compounds 3-14 with different structures were prepared from different starting material compound a, as shown in Table 1.

[0050] Table 1

[0051] Application Examples

[0052] The application performance of the compound of formula (I) of this application was tested by configuring an exemplary photosensitive resin composition.

[0053] 1. Photosensitive resin composition

[0054] The composition is formulated as follows: 100 parts by weight of polyimide resin; 3 parts by weight of purine compound; 5 parts by weight of photoinitiator.

[0055] The polyimide resin is AA-49 produced by Changzhou Lideer Materials Co., Ltd.; the purine compound is the compound shown in general formula (I) of this application or a conventional purine compound used as a comparison; and the photoinitiator is 1-(6-(2-methylbenzoyl)-9-ethylcarbazole-3-yl)-3-cyclopentyl-propane-1-one-acetate oxime ester.

[0056] 2. Preparation of cured film

[0057] The above light-curing composition was stirred to be transparent and uniform under a yellow light lamp, then coated on a silicon wafer using a coater, and dried to form a coating film with a thickness of 16 μm. Then, the coating film was exposed in a crawler-type exposure machine, model RW-UV20101, with a mercury lamp power of 300 W, to obtain a cured film.

[0058] 3. Performance test

[0059] The obtained cured film was subjected to a heating treatment at 320°C for 1 hour under nitrogen protection, and the change in film thickness before and after the treatment was observed to evaluate the heat resistance of the cured film.

[0060] The evaluation results are shown in Table 2.

[0061] Table 2

[0062] Comparative compound 1 is: Comparative compound 2 is Comparative compound 3 is adenine, and comparative compound 4 is

[0063] As can be seen from the above table, the deuterium-substituted purine compound described in the present application, when applied in a curing composition, has a small difference in film thickness before and after baking, excellent heat resistance, and a broad application prospect.

[0064] The applicant declares that the above examples are used to illustrate the nitrogenous adenine, its preparation method and application of the present application, but the present application is not limited to the above examples, i.e. it does not mean that the present application must rely on the above examples to be implemented. It should be understood by those skilled in the art that any improvement of the present application, equivalent replacement of each raw material of the product of the present application, addition of auxiliary ingredients, selection of specific modes, etc. fall within the protection scope and disclosure scope of the present application.

Claims

1. An azaadenine compound having the structure shown in formula (I): wherein R1is selected from hydrogen or deuterium, nitro or cyano, and R2is selected from a linear or branched C1-C20 alkyl group, a C3-C10 cycloalkyl group, a C6-C12 aryl group, or a C6-C18 aryloxyalkyl group.

2. The azanucleoside compound of claim 1, wherein, R2is selected from any one of methyl, ethyl, butyl, isopropyl, tert-butyl, n-propyl, isopropyl, n-butyl, isobutyl, cyclohexyl, phenyl, benzyl or where the wavy line indicates the site of attachment of the group.

3. The aza-adenine compound according to claim 1 or 2, wherein, The azanucleoside is selected from any one of the following compounds:

4. The method of claim 1-3 for preparing an aza-adenine compound, comprising the following steps: I. Synthesis of non-deuterium bearing product: starting material a is reacted with starting material b to give product A, the reaction scheme is as follows: II. Synthesis of deuterium-labeled product: (1) the starting material a reacts with deuterium-labeled trifluorosubstituted sulfonic acid to obtain product B; (2) Product B is reacted with starting material b to give deuterated product C, as shown in the following reaction scheme:

5. The production method according to claim 4, wherein In I, the reaction is carried out in a solvent selected from any one or a combination of at least two of dimethylformamide, dimethylacetamide, dimethylsulfoxide or N-methylpyrrolidone; Optionally, in I, the reaction is carried out in the presence of an acid binding agent; Optionally, in I, the acid binding agent is selected from any one or a combination of at least two of morpholine, piperidine, triethylamine or 4-dimethylaminopyridine; Optionally, in I, the molar ratio of the starting material a to the starting material b is 1.0:1.2-1.0:3.0; Optionally, in I, the reaction is carried out under stirring at room temperature; Optionally, in I, the reaction time is 4-24 h.

6. The production method according to claim 4, wherein In step (1), the molar ratio of the starting material a to deuterium-labeled trifluoromethylsulfonic acid is 1:5-1:20; Optionally, in step (1), the reaction is carried out in a solvent selected from any one or a combination of at least two of tetrahydrofuran, hexahydro-pyran, 1,4-dioxane or 4-methylpyran; Optionally, in step (1), the reaction temperature is 60-130 °C and the reaction time is 12-48 h.

7. The production method according to any one of claims 4 to 6, wherein In step (2), the molar ratio of the product B to the starting material b is 1.0:1.2-1.0:3.0; Optionally, in step (2), the reaction is carried out in a solvent selected from any one or a combination of at least two of dimethylformamide, dimethylacetamide, dimethylsulfoxide or N-methylpyrrolidone; Optionally, in step (2), the reaction is carried out in the presence of an acid binding agent; Optionally, the acid binding agent is selected from any one or a combination of at least two of morpholine, piperidine, triethylamine or 4-dimethylaminopyridine; Optionally, in step (2), the reaction is carried out under stirring at room temperature; Optionally, in step (2), the reaction time is 4-24 h.

8. Use of the aza-adenine compound according to any one of claims 1-3 in a polyimide material.

9. A photosensitive composition comprising a polyimide resin, the aza-adenine compound according to any one of claims 1-3, and a photo-initiator.

10. The photosensitive composition according to claim 9, wherein The contents of the components in the photosensitive composition are: 100 parts by mass of the polyimide resin, 1-10 parts by mass of the aza-adenine compound as described above, and 0.5-10 parts by mass of the photo-initiator; Optionally, the initiator is selected from any one of or a combination of at least two of 1-(6-(2-methylbenzoyl)-9-ethylcarbazol-3-yl)-3-cyclopentyl-propan-1-one-acetic acid oxime ester, 1-(4-phenylthiophenyl)-n-octane-1,2-dione-2-benzoic acid oxime ester, 1-(6-(2-methylbenzoyl)-9-ethylcarbazol-3-yl)-ethan-1-one-acetic acid oxime ester, NCI-831, NCI-930, NCI-1919, SPI-02, SPI-03, SPI-04, DFI-091, DFI-020, TR-PBG-314, TR-PBG-331, TR-PBG-365, or TR-PBG-380.

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