A method for preparing a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative

Abstract

The present invention relates to the field of pharmaceutical chemicals, and specifically discloses a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2- c ] A method for preparing a quinoline-5-one derivative, wherein the method uses aldehyde, active methylene compound and 4-hydroxyquinoline-2-one as reaction raw materials, uses a solid-supported alkaline ionic liquid as a catalyst, and uses an ethanol aqueous solution as a reaction solvent. The system prepares 2-amino-tetrahydropyrano[3,2- c ] The catalytic activity of quinoline-5-one derivatives is higher, and the reaction time can be greatly reduced under mild conditions.

Description

Technical Field

[0001] The invention relates to a method for preparing a derivative, in particular to a method for preparing a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative, and belongs to the field of pharmaceutical chemical industry. Background Art

[0002] In recent years, pyranoquinolinone derivatives have become a major trend in the development of chemical drugs due to their wide range of biological and pharmacological activities that meet the requirements of future drug development. Drugs with pyranoquinolinone parent structures can be used for antifungal, anticytotoxic, antiplatelet aggregation, antihypertension, treatment of estrogen disorders, etc. Therefore, they are very important pharmaceutical intermediates, and their preparation has also attracted widespread attention from chemists.

[0003] Amino-tetrahydropyrano[3,2-c]quinoline-5-one derivatives are important pyranoquinoline derivatives, which can be prepared by a one-pot method, i.e., from aromatic aldehydes, active methylene compounds and 4-hydroxyquinoline-2-one under the catalysis of a catalyst. The catalyst used can be an inorganic salt and an amine-containing organic compound. For example, regarding inorganic salts as catalysts: in 2005, Wang Xiangshan et al. used alumina-supported potassium fluoride as a catalyst, various aromatic aldehydes, cyanoacetic acid esters and 4-hydroxyquinoline-2-one as reaction raw materials, and ethanol as a reaction solvent to prepare a series of 2-amino-4-aryl-5,6-dihydro-4H-pyrano[3,2-c]quinoline-5-one-3-carboxylate derivatives (One-step synthesis of 2-amino-4-aryl-5,6-dihydro-4H-pyrano[3,2-c]quinoline-5-one-3-carboxylate derivatives catalyzed by KF-alumina [J], Organic Chemistry, 2005, 25(5): 579-582); in 2011, Lei Min et al. used ammonium acetate as a catalyst, various aldehydes (lower aliphatic aldehydes, aromatic aldehydes, 2-furancarboxaldehyde, 4-pyridinecarboxaldehyde), malononitrile and 4-hydroxyquinoline-2-one as reaction raw materials, and prepared 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one derivatives in refluxing ethanol (A green, efficient, and rapid procedure for the synthesis of 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinolin-5-one derivatives catalyzed by ammoniumacetate[J], Tetrahedron Letters, 2011, 52: 2597-2600); in 2017, Han et al. Liangliang et al. used diammonium hydrogen phosphate as a recyclable catalyst for the rapid and green synthesis of 2-amino-1,4,5,6-tetrahydropyano[3,2-c]-quinolin-5-one derivatives [J], Polycyclic Aromatic Compounds, 2017, 37(1): 73-80, as catalyst, aromatic aldehydes, malononitrile or ethyl cyanoacetate, and 4-hydroxyquinoline-2-one as reaction raw materials under reflux conditions of ethanol-water solution.

[0004] Regarding amine-containing organic compounds as catalysts: In 2012, Vetrivel Nadaraj et al. used triethylamine as a catalyst, aromatic aldehydes, ethyl cyanoacetate and 4-hydroxyquinoline-2-one as reaction raw materials, and prepared 2-amino-3-ethoxy-4-benzopyrano[3,2-c]quinoline-5(6H)-one derivatives under solvent-free ultrasound-assisted conditions (Microwave solvent-free condition synthesis and pharmacological evaluation of pyrano[3,2-c]quinolines[J], Medicinal Chemistry In 2012, Yao Mengjian used glycine as a green catalyst, aromatic aldehydes or 2-furanaldehyde, malononitrile and 4-hydroxyquinoline-2-one as reaction materials, and prepared 2-amino-3-cyano-1,4,5,6-tetrahydropyrano[3,2-c]quinoline-5-one derivatives under reflux conditions of ethanol aqueous solution (Research on Green and Efficient Synthesis of Pyranoquinoline Derivatives [D], Southwest University In 2020, Lu Hua et al. used magnetic nanomaterials containing amine groups as catalysts, aromatic aldehydes, cyanoacetates and 4-hydroxyquinoline-2-one as reaction raw materials, and prepared 2-amino-3-ethoxy-4-benzopyrano[3,2-c]quinoline-5(6H)-one derivatives in ethanol reflux (A method for preparing pharmaceutical intermediates pyranoquinoline derivatives [P], application number: 2020105534509).

[0005] However, the above preparation method will produce many shortcomings in the process of industrial large-scale production, such as: 1) although a small number of catalysts can be recycled, the preparation process of the catalyst is relatively complicated and the raw materials are expensive; 2) the catalyst needs to be treated before recycling, and the number of recycling times is relatively small; 3) the catalytic efficiency and reaction selectivity of the catalyst are low, resulting in more side reactions and by-products and longer reaction time; 4) since the catalyst cannot be recycled or cannot be regenerated, the entire production process is an intermittent operation and cannot be produced continuously.

[0006] In view of this, it is necessary to provide a method for preparing a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative suitable for industrial large-scale production. Summary of the invention

[0007] In view of the problems in the prior art, the present invention provides a method for preparing a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative.

[0008] The purpose of the present invention can be achieved through the following technical solutions:

[0009] A preparation method of a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative, the preparation method uses aldehyde, active methylene compound and 4-hydroxyquinoline-2-one as reaction raw materials, uses a solid-supported alkaline ionic liquid as a catalyst, and uses an ethanol aqueous solution as a reaction solvent for preparation;

[0010] The chemical reaction formula of the preparation method is:

[0011]

[0012] Wherein, R1 is selected from: C6H5-, 4-FC6H5-, 4-ClC6H5-, 4-BrC6H5-, 4-CH3C6H5-, 4-CH3OC6H5-, 4-NO2C6H5-, 4-OHC6H5-, 2-ClC6H5-, 3-ClC6H5-, 3-BrC6H5-, 3-NO2C6H5-, 2,4-Cl2C6H5-, 3,4-Cl2C6H5-, 2-Furyl, 4-Pyridyl;

[0013] R2 is selected from: CN-, CH3CH2COO-, CH3COO-;

[0014] And the preparation method comprises the following steps:

[0015] Step 1: first, add an ethanol aqueous solution with an ethanol mass ratio of 93-97% into a reaction container, then add aldehyde, active methylene compound and 4-hydroxyquinoline-2-one, mix well, and add a solid-supported alkaline ionic liquid catalyst under continuous stirring to form a suspended reaction liquid;

[0016] Step 2: uniformly heating the reaction solution in an oil bath to reflux, maintaining reflux under constant temperature stirring until the raw material point disappears and the reaction is completed, then immediately stopping stirring and heating, filtering while hot, and obtaining a first filtrate and a first filter residue;

[0017] Step 3: Cool the first filtrate naturally to room temperature, precipitate a solid, crush the solid, let it stand and filter it to obtain a second filtrate and a second filter residue, wash the second filter residue with an ethanol aqueous solution with an ethanol mass ratio of 93 to 97%, and then vacuum dry it at 85° C. for 24 hours to obtain a 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative;

[0018] Step 4: directly add the first filter residue and the reaction raw materials aldehyde, active methylene compound and 4-hydroxyquinoline-2-one prepared in the same proportion as the step to the second filtrate, and carry out the next round of cyclic reaction according to the above steps 2 and 3.

[0019] Optionally, the reaction time of maintaining reflux in step 2 is 13 to 37 minutes.

[0020] Optionally, in step 1, the molar ratio of the aldehyde, the active methylene compound and 4-hydroxyquinoline-2-one is 1:1:1.

[0021] Optionally, the volume amount of the ethanol aqueous solution in milliliters is 6 to 10 times the amount of the aldehyde substance in millimoles.

[0022] Alternatively, the mass of the supported basic ionic liquid catalyst in grams is 4 to 9% of the amount of substance of the aldehyde used in millimoles.

[0023] Optionally, the chemical structural formula of the immobilized alkaline ionic liquid catalyst is:

[0024]

[0025] in: For polystyrene.

[0026] Optionally, the aldehyde is any one of benzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, p-bromobenzaldehyde, p-tolualdehyde, p-methoxybenzaldehyde, p-nitrobenzaldehyde, p-hydroxybenzaldehyde, o-chlorobenzaldehyde, m-chlorobenzaldehyde, m-bromobenzaldehyde, m-nitrobenzaldehyde, 2,4-dichlorobenzaldehyde, 3,4-dichlorobenzaldehyde, 2-furanaldehyde, and 4-pyridinealdehyde.

[0027] Optionally, the active methylene compound is any one of malononitrile, methyl cyanoacetate and ethyl cyanoacetate.

[0028] Beneficial effects of the present invention:

[0029] 1. The present invention uses aldehyde, active methylene compound and 4-hydroxyquinoline-2-one as reaction raw materials, selects a catalytic system consisting of a solid-supported alkaline ionic liquid as a catalyst and an ethanol aqueous solution as a reaction solvent. The system has high catalytic activity when preparing 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivatives, and can greatly reduce the time required for the reaction under mild conditions.

[0030] 2. The present invention has a high selectivity due to the catalytic system composed of the solid-supported alkaline ionic liquid catalyst and the ethanol aqueous solution, which can effectively inhibit the generation of by-products, thereby ensuring that the obtained 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative has a high yield and purity. In addition, the system can be recycled without any treatment after use, and the number of recycling times is large.

[0031] 3. The present invention uses a solid-supported alkaline ionic liquid as a catalyst, which can be regenerated by reflux washing in an organic solvent after multiple cycles of use, and the regenerated catalyst still has high catalytic activity and selectivity.

[0032] 4. The present invention uses ethanol aqueous solution as the reaction solvent and recrystallization solvent, which can be regenerated by rotary evaporation after repeated use, and the lost part can be supplemented by washing liquid.

[0033] 5. Since the catalytic system of the present invention can be reused and regenerated, the purification process of the product 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative is relatively simple, so that the preparation process can be industrialized for large-scale continuous production, with significant economic, environmental and social benefits. DETAILED DESCRIPTION

[0034] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0035] A preparation method of a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative, the preparation method uses aldehyde, active methylene compound and 4-hydroxyquinoline-2-one as reaction raw materials, uses a solid-supported alkaline ionic liquid as a catalyst, and uses an ethanol aqueous solution as a reaction solvent for preparation;

[0036] The chemical reaction formula of the preparation method is:

[0037]

[0038] Wherein, R1 is selected from: C6H5-, 4-FC6H5-, 4-ClC6H5-, 4-BrC6H5-, 4-CH3C6H5-, 4-CH3OC6H5-, 4-NO2C6H5-, 4-OHC6H5-, 2-ClC6H5-, 3-ClC6H5-, 3-BrC6H5-, 3-NO2C6H5-, 2,4-Cl2C6H5-, 3,4-Cl2C6H5-, 2-Furyl, 4-Pyridyl;

[0039] R2 is selected from: CN-, CH3CH2COO-, CH3COO-;

[0040] And the preparation method comprises the following steps:

[0041] Step 1: first, add an ethanol aqueous solution with an ethanol mass ratio of 93-97% into a reaction container, then add aldehyde, active methylene compound and 4-hydroxyquinoline-2-one, mix well, and add a solid-supported alkaline ionic liquid catalyst under continuous stirring to form a suspended reaction liquid;

[0042] Step 2: uniformly heating the reaction solution in an oil bath to reflux, maintaining reflux under constant temperature stirring until the raw material point disappears and the reaction is completed, then immediately stopping stirring and heating, filtering while hot, and obtaining a first filtrate and a first filter residue;

[0043] Step 3: Cool the first filtrate naturally to room temperature, precipitate a solid, crush the solid, let it stand and filter it to obtain a second filtrate and a second filter residue, wash the second filter residue with an ethanol aqueous solution with an ethanol mass ratio of 93 to 97%, and then vacuum dry it at 85° C. for 24 hours to obtain a 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative;

[0044] Step 4: directly add the first filter residue and the reaction raw materials aldehyde, active methylene compound and 4-hydroxyquinoline-2-one prepared in the same proportion as the step to the second filtrate, and carry out the next round of cyclic reaction according to the above steps 2 and 3.

[0045] As a technical optimization solution of the present invention, the reaction time of maintaining reflux in step 2 is 13 to 37 minutes.

[0046] As a technical optimization scheme of the present invention, in step 1, the molar ratio of the aldehyde, the active methylene compound and 4-hydroxyquinoline-2-one is 1:1:1.

[0047] As a technical optimization solution of the present invention, the volume of the ethanol aqueous solution in milliliters is 6 to 10 times the amount of the aldehyde substance in millimoles.

[0048] As a technical optimization scheme of the present invention, the mass of the solid-supported alkaline ionic liquid catalyst in grams is 4 to 9% of the mass of the aldehyde used in millimoles.

[0049] As a technical optimization solution of the present invention, the chemical structural formula of the immobilized alkaline ionic liquid catalyst is:

[0050]

[0051] in: For polystyrene.

[0052] As a technical optimization scheme of the present invention, the aldehyde is any one of benzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, p-bromobenzaldehyde, p-tolualdehyde, p-methoxybenzaldehyde, p-nitrobenzaldehyde, p-hydroxybenzaldehyde, o-chlorobenzaldehyde, m-chlorobenzaldehyde, m-bromobenzaldehyde, m-nitrobenzaldehyde, 2,4-dichlorobenzaldehyde, 3,4-dichlorobenzaldehyde, 2-furancarboxaldehyde, and 4-pyridinecarboxaldehyde.

[0053] As a technical optimization solution of the present invention, the active methylene compound is any one of malononitrile, methyl cyanoacetate and ethyl cyanoacetate.

[0054] The present invention is further described below in conjunction with specific embodiments.

[0055] Example 1

[0056]

[0057] 1.0 mmol benzaldehyde, 1.0 mmol malononitrile and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 6 mL ethanol aqueous solution (93% by mass of ethanol), and the mixture was uniformly mixed by magnetic stirring at room temperature. Finally, 0.05 g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. The mixture was heated in an oil bath and uniformly refluxed (the vapor of the reaction liquid did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 18 minutes. The raw material point disappeared by TLC (thin plate chromatography) detection, and the stirring was stopped immediately. The mixture was filtered while hot to obtain the first filtrate and the first filter residue. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 93%) and vacuum dried at 85°C for 24 hours to obtain 0.30 g of product. The purity was determined by high performance liquid chromatography to be 99.6%, and the yield was calculated to be 94%.

[0058] The characterization data of the product obtained in this example are as follows:

[0059] Mp>300℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 4.45 (s, 1H), 7.17 ~ 7.33 (m, 9H), 7.51 (t, J = 7.8Hz, 1H), 7.86 (d, J = 8.4Hz, 1H) , 11.69 (s, 1H); IR (KBr): ν = 3380, 3276, 3134, 2852, 2184, 1692, 1590, 1496, 1379, 1248, 1163, 1097, 739, 685cm -1 .

[0060] Example 2

[0061] Reusability of the catalytic system

[0062] The first filter residue was directly put into the second filtrate, and then 1.0 mmol benzaldehyde, 1.0 mmol malononitrile and 1.0 mmol 4-hydroxyquinoline-2-one were added. The next cycle reaction was carried out according to the reaction conditions and operation steps of Example 1. It was used for a total of 6 times. The purity and yield of the product are shown in Table 1.

[0063] Table 1 Effect of the number of times the catalytic system is used on the purity and yield of the product

[0064] Number of times the catalytic system is used purity / % Yield / % 1 99.6 94 2 99.5 94 3 99.3 94 4 99.2 92 5 99.0 90 6 98.8 90

[0065] It can be seen from the data in Table 1 that the catalytic system consisting of the immobilized alkaline ionic liquid and the ethanol aqueous solution (ethanol mass ratio is 93%) can still maintain a high purity and yield of the product after being used 6 times.

[0066] Example 3

[0067] Regeneration of the catalyst system

[0068] The first filter residue after recycling 6 times in Example 2 is directly placed in the catalyst system composed of the second filtrate for vacuum distillation, and the fraction is collected. Then 5 mL of ethyl acetate is added to the residue after distillation, heated to reflux for 30 minutes, and filtered with suction. Then 5 mL of ethyl acetate is added to the filter residue, heated to reflux for 30 minutes, and filtered with suction. This is performed 3 times in total. Finally, the obtained filter residue is vacuum dried at 75°C for 24 hours to obtain the regenerated catalyst. The fraction is supplemented to 6 mL with the washing liquid of the washing product, and the regenerated catalyst is added to form a new catalyst system.

[0069] Example 4

[0070] Reusability of the regenerated catalyst system

[0071] 1.0 mmol benzaldehyde, 1.0 mmol malononitrile and 1.0 mmol 4-hydroxyquinoline-2-one were directly added to the new catalyst system prepared in Example 3, and the reaction was carried out according to the reaction conditions and operating steps of Example 1. Then, the catalyst system was recycled according to the steps of Example 2 for 5 times. The purity and yield of the product are shown in Table 2.

[0072] Table 2 Effect of the number of times the regenerated catalytic system is used on the purity and yield of the product

[0073] Number of times the catalytic system is used purity / % Yield / % 1 99.4 93 2 99.3 94 3 99.1 93 4 99.0 92 5 98.7 90

[0074] It can be seen from the data in Table 2 that the regenerated catalytic system can still be reused and maintain a high purity and yield.

[0075] Example 5

[0076]

[0077] 1.0mmol benzaldehyde, 1.0mmol ethyl cyanoacetate and 1.0mmol 4-hydroxyquinoline-2-one were added to a 50mL three-necked flask with a spherical condenser and a magnetic stirrer containing 8mL ethanol aqueous solution (ethanol mass ratio is 95%), respectively, and magnetic stirring was performed to mix evenly at room temperature, and finally 0.07g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. Oil bath heating was performed to reflux evenly (the reaction liquid vapor did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 29 minutes. TLC (thin plate chromatography) detection was performed, and the raw material point disappeared, and the stirring was stopped immediately, and the first filtrate and the first filter residue were obtained by suction filtration while hot. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 95%) and vacuum dried at 85°C for 24 hours to obtain 0.33 g of product. The purity was determined by high performance liquid chromatography to be 99.3%, and the yield was calculated to be 90%.

[0078] The characterization data of the product obtained in this example are as follows:

[0079] Mp250~252℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 1.08 (t, J = 7.6Hz, 3H), 3.97 (q, J = 7.6Hz, 2H), 7.48 ~ 7.54 (m, 1H), 7.69 (s, 2H), 7.91 (d, J = 8.0Hz, 1H), 11.62 (s , 1H); IR (KBr): ν=3437, 3317, 3229, 3055, 2972, 2886, 2853, 1671, 1614, 1577, 1529, 1496, 1445, 1381, 1282, 1178, 1095, 1028, 847, 760, 696cm -1 .

[0080] Example 6

[0081] Reusability of the catalytic system

[0082] The first filter residue was directly put into the second filtrate, and then 1.0 mmol benzaldehyde, 1.0 mmol ethyl cyanoacetate and 1.0 mmol 4-hydroxyquinoline-2-one were added. The next cycle reaction was carried out according to the reaction conditions and operating steps of Example 5. It was used for a total of 6 times. The purity and yield of the product are shown in Table 3.

[0083] Table 3 Effect of the number of times the catalytic system is used on the purity and yield of the product

[0084] Number of times the catalytic system is used purity / % Yield / % 1 99.3 90 2 99.2 89 3 99.0 90 4 98.9 89 5 98.7 88 6 98.6 86

[0085] It can be seen from the data in Table 3 that the catalytic system consisting of the immobilized alkaline ionic liquid and the ethanol aqueous solution (ethanol mass ratio is 95%) can still maintain a high purity and yield of the product after being used 6 times.

[0086] Example 7

[0087] Regeneration of the catalyst system

[0088] The first filter residue after recycling 6 times in Example 6 is directly placed in the catalyst system composed of the second filtrate for vacuum distillation, and the fraction is collected. Then 6 mL of ethyl acetate is added to the residue after distillation, heated to reflux for 30 min, and filtered with suction. Then 6 mL of ethyl acetate is added to the filter residue, heated to reflux for 30 min, and filtered with suction. This is performed 3 times in total. Finally, the obtained filter residue is vacuum dried at 75° C. for 24 h to obtain the regenerated catalyst. The fraction is supplemented to 8 mL with the washing liquid of the washing product, and the regenerated catalyst is added to form a new catalyst system.

[0089] Example 8

[0090] Reusability of the regenerated catalyst system

[0091] 1.0 mmol benzaldehyde, 1.0 mmol ethyl cyanoacetate and 1.0 mmol 4-hydroxyquinoline-2-one were directly added to the new catalyst system prepared in Example 7, and the reaction was carried out according to the reaction conditions and operating steps of Example 5. Then, the catalyst system was recycled according to the steps of Example 6 and used 5 times. The purity and yield of the product are shown in Table 4.

[0092] Table 4 Effect of the number of times the regenerated catalytic system is used on the product purity and yield

[0093] Number of times the catalytic system is used purity / % Yield / % 1 99.3 89 2 99.1 89 3 98.9 87 4 98.7 85 5 98.5 84

[0094] It can be seen from the data in Table 4 that the regenerated catalytic system can still be reused and maintain a high purity and yield.

[0095] Example 9

[0096]

[0097] 1.0 mmol p-methylbenzaldehyde, 1.0 mmol methyl cyanoacetate and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 8 mL ethanol aqueous solution (95% by mass of ethanol), and the mixture was mixed evenly by magnetic stirring at room temperature. Finally, 0.09 g of a solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction solution. The mixture was heated in an oil bath and evenly refluxed (the vapor of the reaction solution did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 37 minutes. The raw material point disappeared after TLC (thin plate chromatography) detection, and the stirring was stopped immediately. The mixture was filtered while hot to obtain the first filtrate and the first filter residue. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 95%) and vacuum dried at 85°C for 24 hours to obtain 0.32 g of product. The purity was determined by high performance liquid chromatography to be 99.4%, and the yield was calculated to be 88%.

[0098] The characterization data of the product obtained in this example are as follows:

[0099] Mp262~264℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 2.14 (s, 3H),

[0100] 3.48 (s, 3H), 4.72 (s, 1H), 6.93 (d, J=8.0Hz, 2H), 7.06 (d, J=8.0Hz, 2H), 7.18~7.28 (m, 2H), 7.49~7.54 (m, 1H), 7.71 (s, 2H), 7.90 (d, J=7.4Hz, 1H), 11.67 (s, 1H); IR (KBr): ν=3412, 3279, 3194, 3059, 3010, 2953, 284 8, 1677, 1601, 1589, 1443, 1386, 1344, 1291, 1182, 1094, 908, 779, 686cm -1 .

[0101] Example 10

[0102] Reusability of the catalytic system

[0103] The first filter residue was directly put into the second filtrate, and then 1.0 mmol p-tolualdehyde, 1.0 mmol methyl cyanoacetate and 1.0 mmol 4-hydroxyquinoline-2-one were added. The next cycle reaction was carried out according to the reaction conditions and operating steps of Example 9. It was used 6 times in total. The purity and yield of the product are shown in Table 5.

[0104] Table 5 Effect of the number of times the catalytic system is used on the purity and yield of the product

[0105] Number of times the catalytic system is used purity / % Yield / % 1 99.4 88 2 99.2 88 3 99.1 88 4 98.9 86 5 98.8 87 6 98.5 84

[0106] It can be seen from the data in Table 5 that the catalytic system consisting of the immobilized alkaline ionic liquid and the ethanol aqueous solution (ethanol mass ratio is 95%) can still maintain a high purity and yield of the product after being used 6 times.

[0107] Embodiment 11

[0108] Regeneration of the catalyst system

[0109] The first filter residue after recycling 6 times in Example 10 is directly placed in the catalyst system composed of the second filtrate for vacuum distillation, and the fraction is collected. Then 5 mL of ethyl acetate is added to the residue after distillation, heated to reflux for 30 minutes, and filtered with suction. Then 5 mL of ethyl acetate is added to the filter residue, heated to reflux for 30 minutes, and filtered with suction. This is performed 3 times in total. Finally, the obtained filter residue is vacuum dried at 75°C for 24 hours to obtain the regenerated catalyst. The fraction is supplemented to 8 mL with the washing liquid of the washing product, and the regenerated catalyst is added to form a new catalyst system.

[0110] Example 12

[0111] 1.0 mmol p-tolualdehyde, 1.0 mmol methyl cyanoacetate and 1.0 mmol 4-hydroxyquinoline-2-one were directly added to the new catalyst system composed of Example 11, and the reaction was carried out according to the reaction conditions and operating steps of Example 9. Then, the catalyst system was recycled according to the steps of Example 10 and used 5 times. The purity and yield of the product are shown in Table 6.

[0112] Table 6 Effect of the number of times the regenerated catalytic system is used on the product purity and yield

[0113] Number of times the catalytic system is used purity / % Yield / % 1 99.2 87 2 99.1 87 3 98.9 87 4 98.8 86 5 98.4 85

[0114] It can be seen from the data in Table 6 that the regenerated catalytic system can still be reused and maintain a high purity and yield.

[0115] Embodiment 13

[0116]

[0117] 1.0 mmol p-chlorobenzaldehyde, 1.0 mmol malononitrile and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 7 mL ethanol aqueous solution (94% by mass of ethanol), and the mixture was uniformly mixed by magnetic stirring at room temperature. Finally, 0.04 g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. The mixture was heated in an oil bath and uniformly refluxed (the vapor of the reaction liquid did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 13 minutes. The raw material point disappeared by TLC (thin plate chromatography) detection, and the stirring was stopped immediately. The mixture was filtered while hot to obtain the first filtrate and the first filter residue. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 94%) and vacuum dried at 85°C for 24 hours to obtain 0.34 g of product. The purity was determined by high performance liquid chromatography to be 99.6%, and the yield was calculated to be 96%.

[0118] The characterization data of the product obtained in this example are as follows:

[0119] Mp>300℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 4.48 (s, 1H), 7.22 (d, J = 8.4Hz, 2H), 7.26 (s, 2H), 7.31 ~ 7.38 (m, 4H), 7.57 ~ 7.63 (m, 1H), 7.91 (d, J = 8.4 Hz, 1H), 11.77 (s, 1H); IR (KBr): ν = 3354, 3306, 3158, 2940, 2854, 2205, 1681, 1600, 1594, 1488, 1392, 1259, 1179, 1102, 1026, 844, 768cm -1 .

[0120] Embodiment 14

[0121]

[0122] 1.0 mmol p-chlorobenzaldehyde, 1.0 mmol methyl cyanoacetate and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 7 mL ethanol aqueous solution (96% by mass of ethanol), and the mixture was uniformly mixed by magnetic stirring at room temperature. Finally, 0.08 g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. The mixture was heated in an oil bath and uniformly refluxed (the vapor of the reaction liquid did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 30 minutes. The raw material point disappeared by TLC (thin plate chromatography) detection, and the stirring was stopped immediately. The mixture was filtered while hot to obtain the first filtrate and the first filter residue. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 96%) and vacuum dried at 85°C for 24 hours to obtain 0.34 g of product. The purity was determined by high performance liquid chromatography to be 99.2%, and the yield was calculated to be 89%.

[0123] The characterization data of the product obtained in this example are as follows:

[0124] Mp265~267℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 3.51 (s, 3H), 4.77 (s, 1H), 7.19 ~ 7.28 (m, 6H), 7.46 ~ 7.50 (m, 1H), 7.90 (d, J = 8.2Hz, 1H), 7.70 (s, 2H), 11 .69 (s, 1H); IR (KBr): ν=3446, 3348, 3257, 2981, 2900, 1682, 1568, 1523, 1481, 1437, 1379, 1274, 1233, 1157, 1083, 1032, 911, 801, 737cm -1 .

[0125] Embodiment 15

[0126]

[0127] 1.0 mmol p-chlorobenzaldehyde, 1.0 mmol ethyl cyanoacetate and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 8 mL ethanol aqueous solution (96% by mass of ethanol), and the mixture was mixed evenly by magnetic stirring at room temperature. Finally, 0.08 g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. Oil bath heating was performed until refluxed evenly (the vapor of the reaction liquid did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 29 minutes. TLC (thin plate chromatography) detection was performed. When the raw material point disappeared, stirring was stopped immediately, and the mixture was filtered while hot to obtain the first filtrate and the first filter residue. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 96%) and vacuum dried at 85°C for 24 hours to obtain 0.35 g of product. The purity was determined by high performance liquid chromatography to be 99.4%, and the yield was calculated to be 87%.

[0128] The characterization data of the product obtained in this example are as follows:

[0129] Mp276~278℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 1.17 (t, J = 6.6Hz, 3H), 3.98 (q, J = 6.6Hz, 2H), 4.79 (s, 1H), 7.16~7.31 (m, 6H), 7.50~7.55 (m, 1H), 7.74 (s, 2H), 7.9 3 (s, 1H), 11.69 (s, 1H); IR (KBr): ν = 3398, 3275, 3201, 2980, 2914, 1702, 1 621, 1579, 1538, 1493, 1377, 1276, 1256, 1178, 1015, 955, 837, 786, 759cm -1 .

[0130] Example 16

[0131]

[0132] 1.0 mmol p-bromobenzaldehyde, 1.0 mmol ethyl cyanoacetate and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 8 mL ethanol aqueous solution (96% by mass of ethanol), and the mixture was uniformly mixed by magnetic stirring at room temperature. Finally, 0.07 g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. The mixture was heated in an oil bath and uniformly refluxed (the vapor of the reaction liquid did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 27 minutes. The raw material point disappeared after TLC (thin plate chromatography) detection, and the stirring was stopped immediately. The mixture was filtered while hot to obtain the first filtrate and the first filter residue. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 96%) and vacuum dried at 85°C for 24 hours to obtain 0.41 g of product. The purity was determined by high performance liquid chromatography to be 99.1%, and the yield was calculated to be 92%.

[0133] The characterization data of the product obtained in this example are as follows:

[0134] Mp253~255℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 1.14 (t, J = 7.2Hz, 3H), 4.01 (q, J = 7.2Hz, 2H), 4.84 (s, 1H), 7.2 0 (d, J=8.4Hz, 2H), 7.29 (t, J=7.6Hz, 1H), 7.31 (t, J=8.0Hz, 1H), 7.39 (d, J=8.4Hz, 2H), 7.54~7. 58 (m, 1H), 7.78 (s, 2H), 7.97 (d, J = 8.0Hz, 1H), 11.71 (s, 1H); IR (KBr): ν = 3388, 3293, 3200, 306 1, 2942, 2802, 1671, 1611, 1582, 1443, 1369, 1258, 1207, 1170, 1135, 1087, 1019, 892, 860, 744cm -1 .

[0135] Embodiment 17

[0136]

[0137] 1.0 mmol m-nitrobenzaldehyde, 1.0 mmol malononitrile and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 7 mL ethanol aqueous solution (95% by mass of ethanol), and the mixture was mixed evenly by magnetic stirring at room temperature. Finally, 0.08 g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. The mixture was heated in an oil bath and refluxed evenly (the vapor of the reaction liquid did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 31 minutes. The raw material point disappeared by TLC (thin plate chromatography) detection, and the stirring was stopped immediately. The mixture was filtered while hot to obtain the first filtrate and the first filter residue. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 95%) and vacuum dried at 85°C for 24 hours to obtain 0.32 g of product. The purity was determined by high performance liquid chromatography to be 99.4%, and the yield was calculated to be 89%.

[0138] The characterization data of the product obtained in this example are as follows:

[0139] Mp>300℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 4.72 (s, 1H), 7.29~7.34 (m, 2H), 7.40 (s, 2H), 7.58~ 7.64 (m, 2H), 7.73 (d, J=7.8Hz, 1H), 7.92 (d, J=8.4Hz, 1H), 8.02 (s, 1H), 8.10 (d, J=8. 4Hz, 1H), 11.79 (s, 1H); IR (KBr): ν = 3540, 3418, 3321, 3004, 2944, 2853, 2187, 1666, 1645, 1580, 1509, 1440, 1372, 1345, 1242, 1165, 1102, 1006, 890, 824, 749, 698, 672cm -1 .

[0140] Embodiment 18

[0141]

[0142] 1.0 mmol 2,4-dichlorobenzaldehyde, 1.0 mmol malononitrile and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 9 mL ethanol aqueous solution (ethanol mass ratio is 96%), respectively, and magnetic stirring was performed to mix evenly at room temperature, and finally 0.05 g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. Oil bath heating was performed to reflux evenly (the reaction liquid vapor did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 19 minutes. TLC (thin plate chromatography) detection was performed, and the raw material point disappeared, and the stirring was stopped immediately, and the first filtrate and the first filter residue were obtained by suction filtration while hot. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 96%) and vacuum dried at 85°C for 24 hours to obtain 0.36 g of product. The purity was determined by high performance liquid chromatography to be 99.2%, and the yield was calculated to be 93%.

[0143] The characterization data of the product obtained in this example are as follows:

[0144] Mp>300℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 4.97 (s, 1H), 7.11 ~ 7.30 (m, 6H), 7.52 ~ 7.61 (m, 2H), 7.89 (d, J = 8.4Hz, 1H), 11.75 (s, 1H) ; IR (KBr): ν=3351, 3314, 3178, 2959, 2864, 2207, 1679, 1642, 1589, 1487, 1390, 1323, 1269, 1195, 1123, 1050, 861, 758cm -1 .

[0145] Embodiment 19

[0146]

[0147] 1.0mmol 2,4-dichlorobenzaldehyde, 1.0mmol ethyl cyanoacetate and 1.0mmol 4-hydroxyquinoline-2-one were added to a 50mL three-necked flask with a spherical condenser and a magnetic stirrer containing 10mL ethanol aqueous solution (ethanol mass ratio is 97%), respectively, and magnetic stirring was used to mix evenly at room temperature, and finally 0.09g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. Oil bath heating was carried out evenly to reflux (the reaction liquid vapor did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 35min. TLC (thin plate chromatography) detection was performed, and the raw material point disappeared, and the stirring was stopped immediately, and the first filtrate and the first filter residue were obtained by suction filtration while hot. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 97%) and vacuum dried at 85°C for 24 hours to obtain 0.39 g of product. The purity was determined by high performance liquid chromatography to be 99.5%, and the yield was calculated to be 90%.

[0148] The characterization data of the product obtained in this example are as follows:

[0149] Mp252~254℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 1.05 (t, J = 7.2Hz, 3H), 3.93 (q, J = 7.2Hz, 2H) , 5.07(s, 1H), 7.22~7.31(m, 4H), 7.32(s, 1H), 7.50~7.57(m, 1H), 7.82(s, 2H ), 7.94 (s, 1H), 11.56 (s, 1H); IR (KBr): ν = 3384, 3279, 3188, 3121, 2990, 2859 , 1687, 1614, 1585, 1538, 1502, 1368, 1274, 1268, 1173, 1086, 864, 842, 753cm -1 .

[0150] Embodiment 20

[0151]

[0152] 1.0 mmol 3,4-dichlorobenzaldehyde, 1.0 mmol methyl cyanoacetate and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 10 mL ethanol aqueous solution (96% by mass of ethanol), and the mixture was uniformly mixed by magnetic stirring at room temperature. Finally, 0.09 g of a solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction solution. The mixture was heated in an oil bath until refluxed (the vapor of the reaction solution did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 32 minutes. The raw material point disappeared after TLC (thin plate chromatography) detection, and the stirring was stopped immediately. The mixture was filtered while hot to obtain the first filtrate and the first filter residue. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 96%) and vacuum dried at 85°C for 24 hours to obtain 0.37 g of product. The purity was determined by high performance liquid chromatography to be 99.2%, and the yield was calculated to be 89%.

[0153] The characterization data of the product obtained in this example are as follows:

[0154] Mp270~272℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 3.51 (s, 3H), 4.80 (s, 1H), 7.17 (d, J = 8.2Hz, 1H), 7.25 ~7.30 (m, 1H), 7.32 (d, J = 8.2Hz, 1H), 7.41 (s, 1H), 7.45 (d, J = 8.0Hz, 1H), 7.52 ~ 7.58 (m, 1H), 7.80 (s, 2H), 7.93 (d, J=7.4Hz, 1H), 11.74 (s, 1H); IR (KBr): ν=3473, 3392, 3284, 2 983, 2896, 1697, 1618, 1589, 1534, 1499, 1461, 1382, 1275, 1179, 1091, 1026, 890, 766cm -1 .

[0155] Embodiment 21

[0156]

[0157] 1.0 mmol 2-furan carboxaldehyde, 1.0 mmol malononitrile and 1.0 mmol 4-hydroxyquinoline-2-one were added to a 50 mL three-necked flask with a spherical condenser and a magnetic stirrer containing 9 mL ethanol aqueous solution (ethanol mass ratio is 96%), respectively, and magnetic stirring was performed to mix evenly at room temperature, and finally 0.09 g of solid-supported alkaline ionic liquid catalyst was added under stirring to form a turbid reaction liquid. Oil bath heating was performed to reflux evenly (the reaction liquid vapor did not exceed the second ball of the spherical condenser), and the reflux reaction was maintained for 34 minutes. TLC (thin plate chromatography) detection was performed, and the raw material point disappeared, and the stirring was stopped immediately, and the first filtrate and the first filter residue were obtained by suction filtration while hot. The first filtrate was naturally cooled to room temperature, a solid was precipitated and the solid was crushed, allowed to stand and filtered to obtain a second filtrate and a second filter residue. The second filter residue was washed with an ethanol aqueous solution (ethanol mass ratio was 96%) and vacuum dried at 85°C for 24 hours to obtain 0.27 g of product. The purity was determined by high performance liquid chromatography to be 99.3%, and the yield was calculated to be 88%.

[0158] The characterization data of the product obtained in this example are as follows:

[0159] Mp>300℃; 1 H NMR (400MHz, DMSO-d6): δ (ppm) = 4.62 (s, 1H), 6.13 (s, 1H), 6.29 (s, 1H), 7.15 ~ 7.54 (m, 6H), 7.82 (d, J=6.8Hz, 1H), 11.82 (s, 1H); IR (KBr): ν=3309, 3142, 2189, 1677, 1380, 1115, 1006, 732, 520cm -1 .

[0160] The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific embodiments described. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative, characterized in that: The preparation method uses aldehyde, active methylene compound and 4-hydroxyquinoline-2-one as reaction raw materials, uses solid-supported alkaline ionic liquid as catalyst, and uses ethanol aqueous solution as reaction solvent. The chemical reaction formula of the preparation method is: Wherein, R1 is selected from: C6H5-, 4-FC6H5-, 4-ClC6H5-, 4-BrC6H5-, 4-CH3C6H5-, 4-CH3OC6H5-, 4-NO2C6H5-, 4-OHC6H5-, 2-ClC6H5-, 3-ClC6H5-, 3-BrC6H5-, 3-NO2C6H5-, 2,4-Cl2C6H5-, 3,4-Cl2C6H5-, 2-Furyl; R2 is selected from: CN-, CH3CH2OCO-, CH3OCO-; The chemical structural formula of the solid-supported alkaline ionic liquid catalyst is: in: For polystyrene; And the preparation method comprises the following steps: Step 1: first, add an ethanol aqueous solution with an ethanol mass ratio of 93-97% into a reaction container, then add equal amounts of aldehyde, active methylene compound and 4-hydroxyquinoline-2-one, mix well, and add a solid-supported alkaline ionic liquid catalyst under continuous stirring to form a suspended reaction liquid; Step 2: uniformly heating the reaction solution in an oil bath to reflux, maintaining reflux under constant temperature stirring until the raw material point disappears and the reaction is completed, then immediately stopping stirring and heating, filtering while hot, and obtaining a first filtrate and a first filter residue; Step 3: Cool the first filtrate naturally to room temperature, precipitate a solid, crush the solid, let it stand and filter it to obtain a second filtrate and a second filter residue, wash the second filter residue with an ethanol aqueous solution with an ethanol mass ratio of 93 to 97%, and then vacuum dry it at 85° C. for 24 hours to obtain a 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative; Step 4: directly add the first filter residue and the reaction raw materials aldehyde, active methylene compound and 4-hydroxyquinoline-2-one prepared in the same proportion as the second step to the second filtrate, and carry out the next round of cyclic reaction according to the above steps 2 and 3; The aldehyde is any one of benzaldehyde, p-fluorobenzaldehyde, p-chlorobenzaldehyde, p-bromobenzaldehyde, p-tolualdehyde, p-methoxybenzaldehyde, p-nitrobenzaldehyde, p-hydroxybenzaldehyde, o-chlorobenzaldehyde, m-chlorobenzaldehyde, m-bromobenzaldehyde, m-nitrobenzaldehyde, 2,4-dichlorobenzaldehyde, 3,4-dichlorobenzaldehyde, and 2-furanaldehyde; The active methylene compound is any one of malononitrile, methyl cyanoacetate and ethyl cyanoacetate.

2. A method for preparing a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative according to claim 1, characterized in that: The reaction time of maintaining reflux in step 2 is 13 to 37 minutes.

3. A method for preparing a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative according to claim 1, characterized in that: The volume of the ethanol aqueous solution in milliliters is 6 to 10 times the amount of the aldehyde substance in millimoles.

4. A method for preparing a pharmaceutical intermediate 2-amino-tetrahydropyrano[3,2-c]quinoline-5-one derivative according to claim 3, characterized in that: The mass of the solid-supported basic ionic liquid catalyst in grams is 4 to 9% of the amount of substance of the aldehyde used in millimoles.

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