Synthetic method of isopropyl omeprazole

Abstract

The invention belongs to the technical field of preparation of raw material medicines, and relates to a synthesis method of isopropyl omeprazole. The preparation method specifically comprises the following steps: taking 2-amino-6-cyanopyridine as an initial raw material, and carrying out substitution reaction on 2-amino-6-cyanopyridine and isopropyl bromoacetate to obtain an intermediate 3; reducing the intermediate 3 to obtain an intermediate 4, and reacting the intermediate 4 with 1-(4-(chloromethyl) phenyl)-1H-pyrazole to obtain an intermediate 6; and reacting the intermediate 6 with a compound 7 to obtain the isopropyl omega-culture. The method provided by the invention has the advantages of easily available raw materials, simple operation and short reaction steps, and avoids the defects of tedious process and low yield of the original route.

Description

Technical Field

[0001] This invention belongs to the field of active pharmaceutical ingredient preparation technology, and relates to a method for synthesizing isopropyl omedeniprene. Background Technology

[0002] Glaucoma is a neurodegenerative disease of the optic nerve caused by high intraocular pressure, ultimately leading to complete vision loss. The main symptom and risk factor of this disease is elevated intraocular pressure due to excessive aqueous humor in the anterior chamber. Current treatments include surgery, laser therapy, and medication, with medication primarily working by lowering intraocular pressure. Omidenepag isopropyl (OMDI) is the world's first commercially available EP2 receptor agonist. Its mechanism of action involves activating EP2 receptors, increasing aqueous humor outflow through the trabecular meshwork and choroid-scleral pathways, thereby lowering intraocular pressure. The 0.002% OMDI product, marketed as Eybelis, received FDA approval in September 2022 and is currently available in countries such as Japan and South Korea.

[0003] The chemical name of isopropyl omedeniper is N-[6-[[[[4-(1 H -pyrazol-1-yl)phenyl]methyl](3-pyridinylsulfonyl)amino]methyl]-2-pyridinyl]-1-methylethyl ester; CAS No. 1187451-19-9; Relative molecular mass: 520.19; Molecular formula: C 26 H 28 N6O4S; Its structural formula is: Existing synthetic methods for isopropyl omedelipe: Japanese Patent JP2011057633 discloses two synthetic process routes: The first process route uses 2,6-pyridinedicarboxylic acid monoethyl ester as the starting material, which undergoes a Curvature rearrangement, amino substitution, and ester reduction to a hydroxyl group to obtain the first intermediate (I). Then, using fluorobenzonitrile and pyrazole as starting materials, the second intermediate (II) is obtained through amino substitution, cyano reduction, and sulfonation. This intermediate (II) is then reacted with intermediate (I) via a Mitsunobu reaction, followed by ester hydrolysis, and finally esterified with isopropanol to obtain isopropyl omedenipa. This route employs a linear reaction, is lengthy, complex, and expensive, with an overall yield of 23.5%.

[0004] Method 2 also uses 2,6-pyridinedicarboxylic acid monoethyl ester as the starting material, and proceeds through the Curtius rearrangement, amino substitution, ester reduction to alcohol, hydroxyl oxidation to aldehyde, hydroxylation, palladium reduction on carbon, sulfonation, and Mitsunobu reaction to obtain isopropyl omedinipe, with an overall yield of 20.5%.

[0005] Analysis of the two routes revealed that the reactants for synthesizing isopropyl omedenipa are relatively expensive, the reaction steps are lengthy, and the yield is low, which is not conducive to industrial production. Therefore, this invention aims to develop a novel synthetic route with inexpensive and readily available reagents, short synthetic steps, simple operation, high yield, and cost advantages. Summary of the Invention

[0006] The present invention aims to solve the problems of difficult-to-obtain starting materials, harsh reaction conditions, and complicated process routes in the existing synthetic methods for preparing isopropyl omedepene, and provides a synthetic method for isopropyl omedepene.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: A method for synthesizing isopropyl omedeniprene involves using 2-amino-6-cyanopyridine (compound 1) as a starting material, reacting it with isopropyl bromoacetate (compound 2) via a substitution reaction to obtain intermediate 3; reducing intermediate 3 to obtain intermediate 4, and then reacting intermediate 4 with 1-(4-(chloromethyl)phenyl)-1 H The reaction of pyrazole (compound 5) yields intermediate 6; intermediate 6 reacts with (compound 7) to yield isopropyl omedenipa.

[0008] To elaborate further, (1) 2-Amino-6-cyanopyridine (compound 1) reacts with isopropyl bromoacetate (compound 2) in the presence of a base to undergo an amino substitution reaction to obtain intermediate 3; (2) The intermediate 3 obtained above is reduced to obtain intermediate 4: (3) Under the action of a base, intermediate 4 reacts with 1-(4-(chloromethyl)phenyl)-1H-pyrazole (compound 5) to give intermediate 6: (4) Intermediate 6 reacts with (compound 7) under the action of a base to give isopropyl omedeniper: .

[0009] In step (1), 2-amino-6-cyanopyridine (compound 1) and isopropyl bromoacetate (compound 2) are heated to reflux at 40-153°C in a solvent in the presence of a base to undergo an amino substitution reaction to obtain intermediate 3; wherein, the molar ratio of compound 1, compound 2 and base is 1:1 to 4:1 to 5, and the base is an alkali metal carbonate and / or an organic base.

[0010] In step (2), intermediate 3 is dissolved in solvent A, a catalyst is added to the solution, and the reaction is carried out at room temperature with hydrogen in the presence of 2 atmospheres for 3-6 hours. After the reaction, intermediate compound 4 is obtained. The catalyst is Pd / C with a Pd content of 10% or Pd(OH)2 / C with a Pd(OH)2 content of 20%, and the amount of catalyst added is 5%-30% of intermediate 3; solvent A is one or more of methanol, ethanol, isopropanol or ethyl acetate.

[0011] In step (3), intermediate 4 and compound 5 are dissolved in a solvent, then an alkali is added to the dissolved intermediate 4, and then the dissolved compound 5 is added dropwise to the solution of intermediate 4 to react with it to obtain intermediate 6; wherein, the amount of alkali used is usually 1 to 5 times the molar amount of 1 mole of intermediate 4; intermediate 4 and compound 5 are mixed in a ratio of 1:1-2, and the alkali is an alkali metal carbonate and / or an organic base. The solvents used to dissolve intermediate 4 and compound 5 may be the same or different.

[0012] In step (4), intermediate 6 is dissolved in a solvent, then an alkali is added, and then compound 7 is added dropwise to the solution of intermediate 6 to react with it to obtain OMDI; wherein intermediate 6 and compound 7 are mixed in a molar ratio of 1:1-2, and the amount of alkali used is usually 1 to 5 times the molar amount of 1 mole of intermediate 6; the alkali is an alkali metal carbonate and / or an organic base. Preferably, the alkali is an organic base.

[0013] The alkali metal carbonate is one or more of sodium carbonate, potassium carbonate, or cesium carbonate; the organic base is one or more of triethylamine, tributylamine, diisopropylethylamine, pyridine, methylpyridine, 2,6-dimethylpyridine, or 4-dimethylaminopyridine.

[0014] The solvent is an inert solvent.

[0015] The inert solvent is one or more of the following: ethers, nitriles, esters, aromatic hydrocarbons, amides, and sulfoxides.

[0016] The ethers are one or more of tetrahydrofuran, 1,4-dioxane, or 1,2-dimethoxyethane; the nitriles are acetonitrile and / or propionitrile; the esters are one or more of methyl formate, ethyl formate, methyl acetate, or ethyl acetate; the aromatic hydrocarbons are one or more of benzene, toluene, or pyridine; the amides are one or more of N,N-dimethylformamide, N,N-dimethylacetamide, or N-methylpyrrolidone; and the sulfoxides are dimethyl sulfoxide. Attached Figure Description

[0017] Figure 1 Example 18, provided as an embodiment of the present invention, shows the purity determination HPLC result of the product isopropyl omedenipa.

[0018] Advantages of this invention: This invention uses 2-amino-6-cyanopyridine (compound 1) as a raw material to obtain intermediate 4 through N-alkylation and reduction reactions, and then reacts intermediate 4 with 1-(4-(chloromethyl)phenyl)-1 H The reaction of pyrazole (compound 5) yields intermediate 6; intermediate 6 reacts with (compound 7) to give isopropyl omedenipa. The synthesis avoids the participation of the expensive 2,6-pyridinedicarboxylic acid monoethyl ester, reducing costs. Furthermore, compared to existing synthetic routes, this method involves only four steps, significantly shortening the reaction time and achieving a high yield of isopropyl omedenipa. This invention solves the problems of difficult-to-obtain starting materials, harsh reaction conditions, and cumbersome processes in existing methods for preparing isopropyl omedenipa. The synthetic route of this invention is short, the materials used in the reaction are readily available, and the reaction operation is simple. Detailed Implementation

[0019] The embodiments of the present invention are described in detail below. These embodiments are implemented based on the technical solution of the present invention, and provide detailed implementation methods and specific operation processes. However, the scope of protection of the present invention is not limited to the following embodiments.

[0020] Example 1 Preparation of intermediate 3: Compound 1 (3.00 g, 25.20 mmol) and compound 2 (9.01 g, 50.40 mmol) were dissolved in acetonitrile (25 mL). Then, DIPEA (6.51 g, 50.40 mmol) was added, and the mixture was heated under reflux for 24 hours. After the reaction was complete, the mixture was concentrated under reduced pressure to obtain crude intermediate 3. Crude intermediate 3 was purified by silica gel column chromatography using petroleum ether:ethyl acetate = 9:1 (v / v) as the eluent to obtain intermediate 3 (3.13 g, yield 56.8%).

[0021] Example 2 Preparation of intermediate 3: Compound 1 (3.00 g, 25.20 mmol) and compound 2 (9.01 g, 50.40 mmol) were dissolved in acetonitrile (25 mL). Then, Cs₂CO₃ (16.42 g, 50.40 mmol) was added, and the mixture was heated under reflux for 24 hours. After the reaction was completed, the mixture was concentrated under reduced pressure to obtain crude intermediate 3, which was purified by column chromatography as described above to obtain intermediate 3 (3.85 g, yield 69.7%).

[0022] Example 3 Preparation of intermediate 3: Compound 1 (3.00 g, 25.20 mmol) and compound 2 (9.01 g, 50.40 mmol) were dissolved in acetonitrile (25 mL). Then, Na₂CO₃ (6.51 g, 50.40 mmol) was added, and the mixture was heated under reflux for 24 hours. After the reaction was completed, the mixture was concentrated under reduced pressure to obtain crude intermediate 3, which was purified by column chromatography as described above to obtain intermediate 3 (2.75 g, yield 49.8%).

[0023] Example 4 Preparation of intermediate 3: Compound 1 (3.00 g, 25.20 mmol) and compound 2 (9.01 g, 50.40 mmol) were dissolved in dichloromethane (25 mL). Then, Cs₂CO₃ (16.42 g, 50.40 mmol) was added, and the mixture was heated under reflux for 24 hours. After the reaction was complete, the mixture was concentrated under reduced pressure to obtain crude intermediate 3, which was then purified by column chromatography as described above to obtain intermediate 3 (3.30 g, yield 59.8%).

[0024] Example 5 Preparation of intermediate 3: Compound 1 (3.00 g, 25.20 mmol) and compound 2 (9.01 g, 50.40 mmol) were dissolved in DMF (25 mL). Then, Cs₂CO₃ (16.42 g, 50.40 mmol) was added, and the mixture was heated under reflux for 24 hours. After the reaction was completed, the crude intermediate 3 was obtained by concentration under reduced pressure. After purification by column chromatography as described above, intermediate 3 (4.46 g, yield 80.8%) was obtained.

[0025] Example 6 Preparation of intermediate 3: Compound 1 (3.00 g, 25.20 mmol) and compound 2 (9.01 g, 50.40 mmol) were dissolved in tetrahydrofuran (25 mL). Then, Cs₂CO₃ (16.42 g, 50.40 mmol) was added, and the mixture was heated under reflux for 24 hours. After the reaction was complete, the crude intermediate 3 was obtained by concentration under reduced pressure. This crude intermediate 3 was then purified by column chromatography as described above to obtain intermediate 3 (3.42 g, yield 61.9%).

[0026] Example 7 Preparation of intermediate 4: Intermediate 3 (2.00 g, 9.12 mmol) obtained in Example 5 was dissolved in methanol (15 mL), followed by the addition of Pd / C (0.20 g, 3.76 mmol) with a Pd content of 10%, and stirred for 3 hours at room temperature in the presence of hydrogen at 2 atm. The mixture was then filtered, the filtrate was collected, and concentrated to obtain intermediate 4 (1.76 g, yield 86.4%).

[0027] Example 8 Preparation of intermediate 4: Intermediate 3 (2.00 g, 9.12 mmol) obtained in Example 5 was dissolved in methanol (15 mL), followed by the addition of Pd(OH)2 / C (0.20 g, 2.84 mmol) with a Pd(OH)2 content of 10%, and stirred for 3 hours at room temperature in the presence of hydrogen at 2 atm. The mixture was then filtered, the filtrate was collected, and concentrated to obtain intermediate 4 (1.68 g, yield 82.5%).

[0028] Example 9 Preparation of intermediate 4: Intermediate 3 (2.00 g, 9.12 mmol) obtained in Example 5 was dissolved in methanol (15 mL), followed by the addition of Pd / C (0.40 g, 3.76 mmol) with a Pd content of 20%, and stirred for 3 hours at room temperature in the presence of hydrogen at 2 atm. The mixture was then filtered, the filtrate was collected, and concentrated to obtain intermediate 4 (1.91 g, yield 93.8%).

[0029] Example 10 Preparation of intermediate 4: Intermediate 3 (2.00 g, 9.12 mmol) obtained in Example 5 was dissolved in methanol (15 mL), followed by the addition of Pd / C (0.60 g, 3.76 mmol) with a Pd content of 30%, and stirred for 3 hours at room temperature in the presence of hydrogen at 2 atm. The mixture was then filtered, the filtrate was collected, and concentrated to obtain intermediate 4 (1.76 g, yield 94.1%).

[0030] Example 11 Preparation of intermediate 4: Intermediate 3 (2.00 g, 9.12 mmol) obtained in Example 5 was dissolved in ethanol (15 mL), followed by the addition of Pd / C (0.40 g, 3.76 mmol) with a Pd content of 20%, and stirred for 3 hours at room temperature in the presence of hydrogen at 2 atm. The mixture was then filtered, the filtrate was collected, and concentrated to obtain intermediate 4 (1.90 g, yield 93.3%).

[0031] Example 12 Preparation of intermediate 6: Intermediate 4 (1.50 g, 6.72 mmol) obtained in Example 11 was mixed with DIPEA (1.74 g, 13.44 mmol) in acetonitrile (20 mL), and 10 mL of acetonitrile solution containing compound 5 (1.29 g, 6.72 mmol) was added dropwise. The mixture was refluxed for 1 hour, and after the reaction, it was slowly cooled to room temperature. The solvent was removed to obtain the crude product, which was purified by column chromatography to obtain intermediate 6 (2.16 g, yield 84.7%).

[0032] Example 13 Preparation of intermediate 6: Intermediate 4 (1.50 g, 6.72 mmol) obtained in Example 11 was mixed with Cs2CO3 (4.38 g, 13.44 mmol) in acetonitrile (20 mL), and 10 mL of acetonitrile solution containing compound 5 (1.29 g, 6.72 mmol) was added dropwise. The mixture was refluxed for 1 hour, and after the reaction, it was slowly cooled to room temperature. The solvent was removed to obtain the crude product, which was purified by column chromatography to obtain intermediate 6 (1.37 g, yield 53.6%).

[0033] Example 14 Preparation of intermediate 6: Intermediate 4 (1.50 g, 6.72 mmol) obtained in Example 11 was mixed with triethylamine (1.36 g, 13.44 mmol) in acetonitrile (20 mL), and 10 mL of acetonitrile solution containing compound 5 (1.29 g, 6.72 mmol) was added dropwise. The mixture was refluxed for 1 hour, and after the reaction, it was slowly cooled to room temperature. The solvent was removed to obtain the crude product, which was purified by column chromatography to obtain intermediate 6 (2.15 g, yield 84.4%).

[0034] Example 15 Preparation of intermediate 6: Intermediate 4 (1.50 g, 6.72 mmol) obtained in Example 11 was mixed with DIPEA (1.74 g, 13.44 mmol) in acetonitrile (20 mL), and 10 mL of acetonitrile solution containing compound 5 (1.29 g, 6.72 mmol) was added dropwise. The mixture was reacted at room temperature for 1 hour, and then slowly cooled to room temperature. The solvent was removed to obtain the crude product, which was purified by column chromatography to obtain intermediate 6 (1.73 g, yield 67.6%).

[0035] Example 16 Preparation of intermediate 6: Intermediate 4 (1.50 g, 6.72 mmol) obtained in Example 11 was mixed with DIPEA (1.74 g, 13.44 mmol) in acetonitrile (20 mL), and 10 mL of acetonitrile solution containing compound 5 (1.29 g, 6.72 mmol) was added dropwise. The mixture was reacted at 60 °C for 1 hour, and then slowly cooled to room temperature. The solvent was removed to obtain the crude product, which was purified by column chromatography to obtain intermediate 6 (2.32 g, yield 90.9%).

[0036] Example 17 Preparation of OMDI: Intermediate 6 (1.50 g, 3.96 mmol) obtained in Example 16 was dissolved in acetonitrile (15 mL), and DIPEA (1.02 g, 7.92 mmol) was added. Compound 7 (0.70 g, 3.96 mmol) was added dropwise under ice bath conditions, and the reaction was carried out for 30 minutes under ice bath conditions. After the reaction was completed, the reaction solution was concentrated to obtain the crude product, which was purified by column chromatography to obtain the final product OMDI (2.06 g, yield 93.2%).

[0037] Example 18 Preparation of OMDI: Intermediate 6 (1.50 g, 3.96 mmol) obtained in Example 16 was dissolved in acetonitrile (15 mL), and cesium carbonate (2.58 g, 7.92 mmol) was added. Compound 7 (0.70 g, 3.96 mmol) was added dropwise under ice bath conditions, and the reaction was carried out for 30 minutes under ice bath conditions. After the reaction was completed, the reaction solution was concentrated to obtain the crude product, which was purified by column chromatography to obtain the final product OMDI (1.65 g, yield 74.8%).

[0038] Example 19 Preparation of OMDI: Intermediate 6 (1.5 g, 3.96 mmol) obtained in Example 16 was dissolved in dichloromethane (15 mL), and DIPEA (1.02 g, 7.92 mmol) was added. Compound 7 (0.70 g, 3.96 mmol) was added dropwise under ice bath conditions, and the reaction was carried out for 30 minutes under ice bath conditions. After the reaction was completed, the reaction solution was concentrated to obtain the crude product, which was purified by column chromatography to obtain the final product OMDI (1.79 g, yield 81.4%).

[0039] Example 20 Preparation of OMDI: Intermediate 6 (1.50 g, 3.96 mmol) obtained in Example 16 was dissolved in acetonitrile (15 mL), and DIPEA (1.02 g, 7.92 mmol) was added. Compound 7 (0.70 g, 3.96 mmol) was added dropwise at room temperature, and the reaction was carried out for 30 minutes at room temperature. After the reaction was completed, the reaction solution was concentrated to obtain the crude product, which was purified by column chromatography to obtain the final product OMDI (1.74 g, yield 84.5%).

[0040] Example 21 Preparation of OMDI: Intermediate 6 (1.5 g, 3.96 mmol) obtained in Example 16 was dissolved in acetonitrile (15 mL), and DIPEA (1.02 g, 7.92 mmol) was added. Compound 7 (0.70 g, 3.96 mmol) was added dropwise at -25°C, and the reaction was carried out at -25°C for 30 minutes. After the reaction was completed, the reaction solution was concentrated to obtain the crude product, which was purified by column chromatography to obtain the final product OMDI (1.78 g, yield 86.5%).

[0041] The structures of the products obtained in the above embodiments, namely isopropyl omedenipe, were confirmed by mass spectrometry and nuclear magnetic resonance. The results are as follows: 1 H NMR (600 MHz, DMSO- d6) δ 8.88 (d, J = 2.3 Hz, 1H), 8.85 – 8.67 (m, 1H), 8.46 (d, J = 2.5 Hz, 1H), 8.08 (ddd, J = 8.0, 2.4, 1.6 Hz, 1H), 7.79 (d, J =8.5 Hz, 2H), 7.73 (d, J = 1.7 Hz, 1H), 7.50 (dd, J = 8.0, 4.8 Hz, 1H), 7.35 (d, J = 8.5 Hz, 2H), 7.25 (dd, J = 8.3, 7.1 Hz, 1H), 6.89 (t, J = 6.0 Hz,1H), 6.53 (t, J = 2.2 Hz, 1H), 6.40 (d, J = 8.3 Hz, 1H), 6.35 (d, J = 7.1 Hz,1H), 4.93 – 4.82 (m, 1H), 4.63 (s, 2H), 4.22 (s, 2H), 3.77 (d, J = 6.1 Hz,2H), 1.10 (d, J = 6.2 Hz, 6H). Mass spectrometry: [M+H] + : 521. 1.

[0042] Furthermore, the purity of the product isopropyl omedinipe was determined by HPLC, and the purity of the products in each example reached over 99%. Meanwhile, the product detection results obtained in Example 18 are as follows... Figure 1 ,Depend on Figure 1 The purity is 99.86%.

Claims

1. A method for synthesizing isopropyl omedelipe, characterized in that: Starting with 2-amino-6-cyanopyridine (compound 1), intermediate 3 was obtained by a substitution reaction with isopropyl bromoacetate (compound 2); intermediate 3 was reduced to intermediate 4, and then intermediate 4 was reacted with 1-(4-(chloromethyl)phenyl)-1 H The reaction of pyrazole (compound 5) yields intermediate 6; intermediate 6 reacts with compound 7 to yield isopropyl omedenipa.

2. The method for synthesizing isopropyl omedeniprene according to claim 1, characterized in that: (1) 2-Amino-6-cyanopyridine (compound 1) reacts with isopropyl bromoacetate (compound 2) in the presence of a base to undergo an amino substitution reaction to obtain intermediate 3; (2) The intermediate 3 obtained above is reduced to obtain intermediate 4: (3) Under the action of a base, intermediate 4 reacts with 1-(4-(chloromethyl)phenyl)-1H-pyrazole (compound 5) to give intermediate 6: (4) Intermediate 6 reacts with compound 7 under the action of a base to give isopropyl omedeniper: 。 3. The method for synthesizing isopropyl omedeniprene according to claim 2, characterized in that: In step (1), 2-amino-6-cyanopyridine (compound 1) and isopropyl bromoacetate (compound 2) are heated to reflux at 40-153°C in the presence of a base in a solvent to undergo an amino substitution reaction to obtain intermediate 3; wherein, compound 1, compound 2 and base are mixed in a molar ratio of 1:1 to 4:1 to 5, and the base is an alkali metal carbonate and / or an organic base.

4. The method for synthesizing isopropyl omedeniprene according to claim 2, characterized in that: In step (2), intermediate 3 is dissolved in solvent A, a catalyst is added to the solution, and the reaction is carried out at room temperature with hydrogen in the presence of 2 atmospheres for 3-6 hours. After the reaction, intermediate compound 4 is obtained. The catalyst is Pd / C with a Pd content of 10% or Pd(OH)2 / C with a Pd(OH)2 content of 20%, and the amount of catalyst added is 5%-30% of the mass of intermediate 3; solvent A is one or more of methanol, ethanol, isopropanol or ethyl acetate.

5. The method for synthesizing isopropyl omedeniprene according to claim 2, characterized in that: In step (3), after intermediate 4 and compound 5 are dissolved in a solvent, an alkali is added to the dissolved intermediate 4, and then the dissolved compound 5 is added dropwise to the solution of intermediate 4 to react with it to obtain intermediate 6; wherein, the amount of alkali used is usually 1 to 5 times the molar amount of 1 mole of intermediate 4; intermediate 4 and compound 5 are mixed in a molar ratio of 1:1-2, and the alkali is an alkali metal carbonate and / or an organic base.

6. The method for synthesizing isopropyl omedeniprene according to claim 2, characterized in that: In step (4), after intermediate 6 is dissolved in a solvent, an alkali is added, and then compound 7 is added dropwise to the solution of intermediate 6 to react with it to obtain OMDI; wherein, intermediate 6 and compound 7 are mixed in a molar ratio of 1:1-2, and the amount of alkali used is usually 1 to 5 times the molar amount of 1 mole of intermediate 6, and the alkali is an alkali metal carbonate and / or an organic base.

7. The method for synthesizing isopropyl omedeniprene according to claim 3, 5 or 6, characterized in that: The alkali metal carbonate is one or more of sodium carbonate, potassium carbonate, or cesium carbonate; the organic base is one or more of triethylamine, tributylamine, diisopropylethylamine, pyridine, methylpyridine, 2,6-dimethylpyridine, or 4-dimethylaminopyridine.

8. The method for synthesizing isopropyl omedeniprene according to claim 3, 5 or 6, characterized in that: The solvent is an inert solvent.

9. The method for synthesizing isopropyl omedeniprene according to claim 3, 5 or 6, characterized in that: The inert solvent is one or more of the following: ethers, nitriles, esters, aromatic hydrocarbons, amides, and sulfoxides.

10. The method for synthesizing isopropyl omedeniprene according to claim 9, characterized in that: The ethers are one or more of tetrahydrofuran, 1,4-dioxane, or 1,2-dimethoxyethane; the nitriles are acetonitrile and / or propionitrile; the esters are one or more of methyl formate, ethyl formate, methyl acetate, or ethyl acetate; the aromatic hydrocarbons are one or more of benzene, toluene, or pyridine; the amides are one or more of N,N-dimethylformamide, N,N-dimethylacetamide, or N-methylpyrrolidone; and the sulfoxides are dimethyl sulfoxide.

Images