CN118546092A - Synthesis method of 7-bromo-1H-indazole-3-methyl formate - Google Patents
Synthesis method of 7-bromo-1H-indazole-3-methyl formate Download PDFInfo
- Publication number
- CN118546092A CN118546092A CN202410603018.4A CN202410603018A CN118546092A CN 118546092 A CN118546092 A CN 118546092A CN 202410603018 A CN202410603018 A CN 202410603018A CN 118546092 A CN118546092 A CN 118546092A
- Authority
- CN
- China
- Prior art keywords
- bromo
- indazole
- reaction
- ethylene glycol
- add
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明涉及有机化学合成技术领域，尤其涉及一种7‑溴‑1H‑吲唑‑3‑甲酸甲酯的合成方法，包括：步骤1、将3‑溴‑2‑氟苯甲醛与N,O‑二甲基羟胺盐酸盐反应得到7‑溴‑1H‑吲唑；步骤2、将7‑溴‑1H‑吲唑与碘反应得到7‑溴‑3‑碘‑1H‑吲唑；步骤3、将7‑溴‑3‑碘‑1H‑吲唑与4,5‑双二苯基膦‑9,9‑二甲基氧杂蒽进行还原反应得到7‑溴‑1H‑吲唑‑3‑甲酸甲酯。本发明以3‑溴‑2‑氟苯甲醛、N,O‑二甲基羟胺盐酸盐、碘与4,5‑双二苯基膦‑9,9‑二甲基氧杂蒽等为原料，经三步反应合成了7‑溴‑1H‑吲唑‑3‑甲酸甲酯，合成路径短，合成方法简单，产品产率高。
The present invention relates to the technical field of organic chemical synthesis, and in particular to a method for synthesizing 7-bromo-1H-indazole-3-methyl formate, comprising: step 1, reacting 3-bromo-2-fluorobenzaldehyde with N,O-dimethylhydroxylamine hydrochloride to obtain 7-bromo-1H-indazole; step 2, reacting 7-bromo-1H-indazole with iodine to obtain 7-bromo-3-iodo-1H-indazole; step 3, reducing 7-bromo-3-iodo-1H-indazole with 4,5-bis-diphenylphosphine-9,9-dimethylxanthene to obtain 7-bromo-1H-indazole-3-methyl formate. The present invention uses 3-bromo-2-fluorobenzaldehyde, N,O-dimethylhydroxylamine hydrochloride, iodine and 4,5-bis-diphenylphosphine-9,9-dimethylxanthene as raw materials, and synthesizes 7-bromo-1H-indazole-3-methyl formate through three-step reaction, with short synthesis path, simple synthesis method and high product yield.
Description
Technical Field
The invention relates to the technical field of organic chemical synthesis, in particular to a method for synthesizing 7-bromo-1H-indazole-3-methyl formate.
Background
The 3-bromo-2-fluorobenzaldehyde is used as a main raw material to synthesize the 7-bromo-1H-indazole-3-methyl formate, the methyl formate group is introduced into the 3-position of the indazole, the metabolic stability of the drug can be regulated, the bromine group is introduced into the 7-position of the indazole, and the compound is used as a hydrogen bond acceptor and a donor, so that the compound can be greatly improved and has higher biological activity. In organic synthesis, as an active intermediate, many types of organic compounds, which have a high pharmacological activity in most cases, can be further synthesized.
At present, 7-bromo-1H-indazole-3-methyl formate is an important medical intermediate, so that the compound has important practical significance in the synthesis research of the compound.
Disclosure of Invention
The invention aims to solve the defects in the prior art, and provides a synthetic method of 7-bromo-1H-indazole-3-methyl formate, which has the advantages of short synthetic route and high product yield.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
a method for synthesizing 7-bromo-1H-indazole-3-methyl formate comprises the following specific steps:
Step 1, adding ethylene glycol dimethyl ether, 3-bromo-2-fluorobenzaldehyde, N, O-dimethylhydroxylamine hydrochloride and potassium carbonate into a reaction bottle, stirring and dissolving, heating to 40 ℃ and keeping the reaction time for 3 hours, evaporating the ethylene glycol dimethyl ether after the reaction is finished, adding 85% hydrazine hydrate and ethylene glycol, stirring, heating to 120 ℃, continuing to react for 12 hours, cooling the reaction solution to 70-75 ℃ after the reaction is finished, pouring into 2000mL of water, extracting for 2 times (2X 2000 mL) by using dichloromethane, concentrating and evaporating to dryness to obtain 7-bromo-1H-indazole;
Step 2, adding N, N-dimethylformamide, 7-bromo-1H-indazole and solid potassium hydroxide into a reaction bottle, starting stirring, heating to 35 ℃, adding iodine in batches, controlling the reaction temperature to be not higher than 35 ℃, reacting for 4 hours, pouring reaction liquid into 4000mL of water after the reaction is finished, adding sodium thiosulfate until the reaction liquid cannot cause wet potassium iodide test paper to turn blue, filtering and drying after stirring to obtain 7-bromo-3-iodo-1H-indazole;
And 3, adding N, N-dimethylformamide, methanol, 7-bromo-3-iodo-1H-indazole, a catalyst, 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene and triethylamine into a reaction bottle, starting stirring, replacing with carbon monoxide for three times, heating to 75 ℃, reacting for 12 hours, steaming 50% of methanol after the reaction is finished, adding 200mL of water, extracting for 4 times (4X 250 mL) by using methyl tertiary butyl ether, and evaporating an extract to dryness to obtain the 7-bromo-1H-indazole-3-methyl formate.
Preferably, in step 1, the 3-bromo-2-fluorobenzaldehyde, N, O-dimethylhydroxylamine hydrochloride, potassium carbonate, 85% hydrazine hydrate, ethylene glycol dimethyl ether and ethylene glycol are used in a mass ratio of 1:0.41-0.62:0.68-0.95:3.94-5.91:3.69-4.83:3.84-4.82.
Preferably, in step 2, the 7-bromo-1H-indazole, iodine, potassium hydroxide and N, N-dimethylformamide are used in a mass ratio of 1:1.69-2.19:0.41-0.56:8.67-10.67.
Preferably, in step 3, the catalyst is any one of palladium acetate, manganese acetate or nickel acetate.
Preferably, in step3, the catalyst is palladium acetate.
Preferably, in step 3, the amount ratio of the 7-bromo-3-iodo-1H-indazole, palladium acetate, 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, triethylamine, N-dimethylformamide and methanol is 1:0.01-0.04:0.11-0.26:9.14-10.88:7.00-8.75:5.75-7.50 by mass.
Compared with the prior art, the invention has the following beneficial effects:
The invention takes 3-bromo-2-fluorobenzaldehyde, N, O-dimethylhydroxylamine hydrochloride, iodine, 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene and the like as raw materials, and synthesizes the 7-bromo-1H-indazole-3-methyl formate through three-step reaction, and has the advantages of short synthesis path, simple synthesis method and high product yield.
Drawings
FIG. 1 is a schematic diagram of the synthetic route of the present invention.
Detailed Description
The following technical solutions in the embodiments of the present invention will be clearly and completely described with reference to the accompanying drawings, so that those skilled in the art can better understand the advantages and features of the present invention, and thus the protection scope of the present invention is more clearly defined. The described embodiments of the present invention are intended to be only a few, but not all embodiments of the present invention, and all other embodiments that may be made by one of ordinary skill in the art without inventive faculty are intended to be within the scope of the present invention.
As shown in FIG. 1, the synthesis method of the 7-bromo-1H-indazole-3-methyl formate comprises the following specific steps:
Step 1, adding ethylene glycol dimethyl ether, 3-bromo-2-fluorobenzaldehyde, N, O-dimethylhydroxylamine hydrochloride and potassium carbonate into a reaction bottle, stirring and dissolving, heating to 40 ℃ and keeping the reaction time for 3 hours, evaporating the ethylene glycol dimethyl ether after the reaction is finished, adding 85% hydrazine hydrate and ethylene glycol, stirring, heating to 120 ℃, continuing to react for 12 hours, cooling the reaction solution to 70-75 ℃ after the reaction is finished, pouring into 2000mL of water, extracting for 2 times (2X 2000 mL) by using dichloromethane, concentrating and evaporating to dryness to obtain 7-bromo-1H-indazole;
Step 2, adding N, N-dimethylformamide, 7-bromo-1H-indazole and solid potassium hydroxide into a reaction bottle, starting stirring, heating to 35 ℃, adding iodine in batches, controlling the reaction temperature to be not higher than 35 ℃, reacting for 4 hours, pouring reaction liquid into 4000mL of water after the reaction is finished, adding sodium thiosulfate until the reaction liquid cannot cause wet potassium iodide test paper to turn blue, filtering and drying after stirring to obtain 7-bromo-3-iodo-1H-indazole;
And 3, adding N, N-dimethylformamide, methanol, 7-bromo-3-iodo-1H-indazole, a catalyst, 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene and triethylamine into a reaction bottle, starting stirring, replacing with carbon monoxide for three times, heating to 75 ℃, reacting for 12 hours, steaming 50% of methanol after the reaction is finished, adding 200mL of water, extracting for 4 times (4X 250 mL) by using methyl tertiary butyl ether, and evaporating an extract to dryness to obtain the 7-bromo-1H-indazole-3-methyl formate.
The specific synthetic route is as follows:
Specifically, adding ethylene glycol dimethyl ether, 3-bromo-2-fluorobenzaldehyde, N, O-dimethylhydroxylamine hydrochloride and potassium carbonate into a reaction bottle, stirring and dissolving, heating to 40 ℃ and keeping the reaction time for 3 hours, evaporating the ethylene glycol dimethyl ether after the reaction is finished, adding 85% hydrazine hydrate and ethylene glycol, stirring, heating to 120 ℃, continuing to react for 12 hours, cooling the reaction solution to 70-75 ℃ after the reaction is finished, pouring into 2000mL of water, extracting for 2 times (2X 2000 mL) by using dichloromethane, concentrating and evaporating to dryness, and obtaining 7-bromo-1H-indazole. In the invention, 3-bromo-2-fluorobenzaldehyde, N, O-dimethylhydroxylamine hydrochloride, potassium carbonate and 85% hydrazine hydrate are used in a mass ratio of 1:0.41-0.62:0.68-0.95:3.94-5.91:3.69-4.83:3.84-4.82.
Adding N, N-dimethylformamide, 7-bromo-1H-indazole and solid potassium hydroxide into a reaction bottle, starting stirring, heating to 35 ℃, adding iodine in batches, controlling the reaction temperature to be not higher than 35 ℃, reacting for 4 hours, pouring the reaction liquid into 4000mL of water after the reaction is finished, adding sodium thiosulfate until the wet potassium iodide test paper cannot turn blue, stirring, filtering, and drying to obtain 7-bromo-3-iodo-1H-indazole. In the invention, the dosage ratio of the 7-bromine-1H-indazole, iodine, potassium hydroxide and N, N-dimethylformamide is 1:1.69-2.19:0.41-0.56:8.67-10.67 by mass.
Adding N, N-dimethylformamide, methanol, 7-bromo-3-iodo-1H-indazole, a catalyst, 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene and triethylamine into a reaction bottle, starting stirring, replacing with carbon monoxide for three times, heating to 75 ℃, reacting for 12 hours, evaporating 50% of methanol, adding 200mL of water, extracting with methyl tertiary butyl ether for 4 times (4X 250 mL), and evaporating the extract to dryness to obtain 7-bromo-1H-indazole-3-methyl formate. In the invention, the catalyst is one of palladium acetate, manganese acetate or nickel acetate, preferably palladium acetate, 7-bromo-3-iodo-1H-indazole, palladium acetate, 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene, triethylamine, N-dimethylformamide and methanol, and the dosage ratio is 1:0.01-0.04:0.11-0.26:9.14-10.88:7.00-8.75:5.75-7.50 by mass.
In order to further understand the present invention, the synthesis method provided by the present invention is described in detail with reference to the following examples, and the scope of the present invention is not limited by the following examples.
Example 1
Step1, synthesis of 7-bromo-1H-indazole:
750g of ethylene glycol dimethyl ether, 203g of 3-bromo-2-fluorobenzaldehyde, 83.5g of N, O-dimethylhydroxylamine hydrochloride and 138g of potassium carbonate are added into a reaction bottle, stirred and dissolved, the reaction time is kept for 3 hours at the temperature of 40 ℃, after the reaction is finished, the ethylene glycol dimethyl ether is distilled off, 800g of 85% hydrazine hydrate and 780g of ethylene glycol are added, stirred and heated to 120 ℃ for continuous reaction for 12 hours, after the reaction is finished, the reaction solution is cooled to 70-75 ℃, poured into 2000mL of water, extracted for 2 times (2X 2000 mL) by methylene dichloride, and concentrated and evaporated to dryness, thus obtaining 150.0g of 7-bromo-1H-indazole, and the product yield is 76.11%.
Step2, synthesis of 7-bromo-3-iodo-1H-indazole:
1300g of N, N-dimethylformamide, 150g of 7-bromo-1H-indazole and 61.6g of solid potassium hydroxide are added into a reaction bottle, stirring is started, the temperature is raised to 35 ℃, 253g of iodine is added in batches, the reaction temperature is controlled to be not higher than 35 ℃, the reaction time is 4 hours, after the reaction is finished, the reaction solution is poured into 4000mL of water, sodium thiosulfate is added until the wet potassium iodide test paper cannot turn blue, after stirring, filtration and drying are carried out, and 223g of 7-bromo-3-iodo-1H-indazole is obtained, and the product yield is 91.12%.
Step 3, synthesis of 7-bromo-1H-indazole-3-carboxylic acid methyl ester:
140g of N, N-dimethylformamide, 115g of methanol, 20g of 7-bromo-3-iodo-1H-indazole, 0.28g of palladium acetate, 2.2g of 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene and 182.8 of triethylamine are added into a reaction bottle, stirring is started, carbon monoxide is used for three times, the temperature is raised to 75 ℃, the reaction time is 12 hours, after the reaction is finished, 50% of methanol is distilled off, 200mL of water is added, 4 times (4X 250 mL) of methyl tertiary butyl ether is used for extraction, the extract is evaporated to dryness, and 9.7g of 7-bromo-1H-indazole-3-methyl formate can be obtained, and the product yield is 60.34%.
Example 2
Step1, synthesis of 7-bromo-1H-indazole:
980g of ethylene glycol dimethyl ether, 203g of 3-bromo-2-fluorobenzaldehyde, 125.3g of N, O-dimethylhydroxylamine hydrochloride and 193.2g of potassium carbonate are added into a reaction bottle, stirred and dissolved, the reaction time is kept for 3 hours at the temperature of 40 ℃, after the reaction is finished, the ethylene glycol dimethyl ether is distilled off, 1200g of 85% hydrazine hydrate and 980g of ethylene glycol are added, the stirring is carried out, the temperature is increased to 120 ℃ for continuing the reaction for 12 hours, after the reaction is finished, the reaction solution is cooled to 70-75 ℃, poured into 2000mL of water, extracted for 2 times (2X 2000 mL) by methylene dichloride, concentrated and evaporated to dryness, and 147.9g of 7-bromo-1H-indazole is obtained, and the product yield is 75.03%.
Step2, synthesis of 7-bromo-3-iodo-1H-indazole:
1600g of N, N-dimethylformamide, 150g of 7-bromo-1H-indazole and 84g of solid potassium hydroxide are added into a reaction bottle, stirring is started, the temperature is raised to 35 ℃, 329g of iodine is added in batches, the reaction temperature is controlled to be not higher than 35 ℃, the reaction time is 4 hours, after the reaction is finished, the reaction solution is poured into 4000mL of water, sodium thiosulfate is added until the wet potassium iodide test paper cannot turn blue, after stirring, filtering and drying are carried out, and the 7-bromo-3-iodo-1H-indazole 195.9g is obtained, and the product yield is 88.01%.
Step 3, synthesis of 7-bromo-1H-indazole-3-carboxylic acid methyl ester:
175g of N, N-dimethylformamide, 150g of methanol, 20g of 7-bromo-3-iodo-1H-indazole, 0.84g of palladium acetate, 5.2g of 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene and triethylamine 218 are added into a reaction bottle, stirring is started, carbon monoxide is used for three times, the temperature is raised to 75 ℃, the reaction time is 12H, 50% of methanol is distilled off after the reaction is finished, 200mL of water is added, 4 times (4X 250 mL) of methyl tertiary butyl ether is used for extraction, the extract is evaporated to dryness, and 8.9g of 7-bromo-1H-indazole-3-methyl formate can be obtained, and the product yield is 55.63%.
Example 3
Step1, synthesis of 7-bromo-1H-indazole:
850g of ethylene glycol dimethyl ether, 203g of 3-bromo-2-fluorobenzaldehyde, 105g of N, O-dimethylhydroxylamine hydrochloride and 165g of potassium carbonate are added into a reaction bottle, stirred and dissolved, the reaction time is kept for 3 hours at the temperature of 40 ℃, after the reaction is finished, the ethylene glycol dimethyl ether is distilled off, then 1000g of 85% hydrazine hydrate and 850g of ethylene glycol are added, stirred and heated to 120 ℃, the reaction is continued for 12 hours, after the reaction is finished, the reaction solution is cooled to 70-75 ℃, poured into 2000mL of water, extracted for 2 times (2X 2000 mL) by methylene dichloride, concentrated and evaporated to dryness, and 153.6g of 7-bromo-1H-indazole is obtained, and the product yield is 77.91%.
Step2, synthesis of 7-bromo-3-iodo-1H-indazole:
1450g of N, N-dimethylformamide, 150g of 7-bromo-1H-indazole and 73g of solid potassium hydroxide are added into a reaction bottle, stirring is started, the temperature is raised to 35 ℃, 290g of iodine is added in batches, the reaction temperature is controlled to be not higher than 35 ℃, the reaction time is 4 hours, after the reaction is finished, the reaction solution is poured into 4000mL of water, sodium thiosulfate is added until the wet potassium iodide test paper cannot turn blue, after stirring, filtration and drying are carried out, and the 7-bromo-3-iodo-1H-indazole 221g is obtained, and the product yield is 90.26%.
Step 3, synthesis of 7-bromo-1H-indazole-3-carboxylic acid methyl ester:
155g of N, N-dimethylformamide, 135g of methanol, 20g of 7-bromo-3-iodo-1H-indazole, 0.56g of palladium acetate, 3.7g of 4, 5-bis-diphenylphosphine-9, 9-dimethyl xanthene and triethylamine 205 are added into a reaction bottle, stirring is started, carbon monoxide is used for three times, the temperature is raised to 75 ℃, the reaction time is 12 hours, 50% of methanol is distilled off after the reaction is finished, 200mL of water is added, 4 times (4X 250 mL) of methyl tertiary butyl ether is used for extraction, the extract is evaporated to dryness, and 9.5g of 7-bromo-1H-indazole-3-methyl formate can be obtained, and the product yield is 59.38%.
In summary, the invention takes 3-bromo-2-fluorobenzaldehyde, N, O-dimethylhydroxylamine hydrochloride, iodine, 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene and the like as raw materials, and synthesizes the 7-bromo-1H-indazole-3-methyl formate through three-step reaction, thus having short synthetic path, simple synthetic method and high product yield.
The description and practice of the invention disclosed herein will be readily apparent to those skilled in the art, and may be modified and adapted in several ways without departing from the principles of the invention. Accordingly, modifications or improvements may be made without departing from the spirit of the invention and are also to be considered within the scope of the invention.
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410603018.4A CN118546092A (en) | 2024-05-15 | 2024-05-15 | Synthesis method of 7-bromo-1H-indazole-3-methyl formate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410603018.4A CN118546092A (en) | 2024-05-15 | 2024-05-15 | Synthesis method of 7-bromo-1H-indazole-3-methyl formate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118546092A true CN118546092A (en) | 2024-08-27 |
Family
ID=92447288
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410603018.4A Pending CN118546092A (en) | 2024-05-15 | 2024-05-15 | Synthesis method of 7-bromo-1H-indazole-3-methyl formate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118546092A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3135667A1 (en) * | 2014-04-24 | 2017-03-01 | Mitsubishi Tanabe Pharma Corporation | Novel 2-amino-pyridine and 2-amino-pyrimidine derivatives and medicinal use thereof |
| CN110590673A (en) * | 2019-09-02 | 2019-12-20 | 南通大学 | A kind of 4-chloro-7-methyl-1H-indazole and its chemical synthesis method |
| WO2020210828A1 (en) * | 2019-04-12 | 2020-10-15 | Hibercell, Inc. | (aza)indazolyl-aryl sulfonamide and related compounds and their use in treating medical conditions |
| CN117304113A (en) * | 2023-09-15 | 2023-12-29 | 南通大学 | A kind of synthesis method of 5-(trifluoromethoxy)-1H-indazole-3-carboxylic acid methyl ester |
-
2024
- 2024-05-15 CN CN202410603018.4A patent/CN118546092A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3135667A1 (en) * | 2014-04-24 | 2017-03-01 | Mitsubishi Tanabe Pharma Corporation | Novel 2-amino-pyridine and 2-amino-pyrimidine derivatives and medicinal use thereof |
| WO2020210828A1 (en) * | 2019-04-12 | 2020-10-15 | Hibercell, Inc. | (aza)indazolyl-aryl sulfonamide and related compounds and their use in treating medical conditions |
| CN110590673A (en) * | 2019-09-02 | 2019-12-20 | 南通大学 | A kind of 4-chloro-7-methyl-1H-indazole and its chemical synthesis method |
| CN117304113A (en) * | 2023-09-15 | 2023-12-29 | 南通大学 | A kind of synthesis method of 5-(trifluoromethoxy)-1H-indazole-3-carboxylic acid methyl ester |
Non-Patent Citations (3)
| Title |
|---|
| HORNBROOK, LAUREN F.等: "Bromination of indazoles enhanced by organic-dye, visible-light photoredox catalysis", TETRAHEDRON, vol. 142, 31 December 2023 (2023-12-31), pages 133523 * |
| LIN, SONGNIAN等: "A novel series of indazole-/indole-based glucagon receptor antagonists", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 25, no. 19, 31 December 2015 (2015-12-31), pages 4143 - 4147, XP029264264, DOI: 10.1016/j.bmcl.2015.08.015 * |
| NORRIS, STEPHEN等: "Design and synthesis of novel cereblon binders for use in targeted protein degradation", JOURNAL OF MEDICINAL CHEMISTRY, vol. 66, no. 23, 22 November 2023 (2023-11-22), pages 16388 - 16409, XP093208876, DOI: 10.1021/acs.jmedchem.3c01848 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111423452B (en) | Intermediates of Relugoli and their preparation methods and applications | |
| CN105061373B (en) | A kind of synthetic method of Dapagliflozin isomer impurities | |
| JP5395908B2 (en) | Process for producing 4- (1-hydroxy-1-methylethyl) -2-propylimidazole-5-carboxylic acid ester | |
| CN103601749B (en) | A kind of synthetic method of 1-alkyl pyrazole-4-pinacol borate | |
| CN107253912B (en) | Synthetic method of cyhalofop-butyl | |
| CN112079848A (en) | Synthesis method of baroxavir key intermediate | |
| CN106977572A (en) | A kind of method using hyodesoxycholic acid as Material synthesis lithocholic acid | |
| CN107011404B (en) | A method of using cholic acid as Material synthesis lithocholic acid | |
| CN110551023B (en) | A kind of method for preparing alkyl dioic acid monobenzyl ester | |
| CN118754880A (en) | A method for preparing a cyclopropyl-substituted 2H-benzofuran compound intermediate | |
| CN118546092A (en) | Synthesis method of 7-bromo-1H-indazole-3-methyl formate | |
| CN116693437A (en) | Synthesis method of N-Boc-3-azetidineacetic acid | |
| CN102336721B (en) | Method for synthesizing AE-active ester by using water-containing 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid | |
| CN111233748A (en) | Synthesis of tirofiban hydrochloride | |
| CN115710213A (en) | Preparation method of cis-chiral 3-fluoro-4-hydroxypiperidine and derivatives thereof | |
| CN104387259A (en) | Method for preparing 2,4,5-trifluorophenylacetic acid | |
| CN111072450B (en) | Synthesis method of allyl alcohol derivative | |
| CN114315697A (en) | Preparation method of tirofiban hydrochloride | |
| CN107200763A (en) | A kind of method using chenodeoxycholic acid as Material synthesis lithocholic acid | |
| CN112979553A (en) | Synthesis method of dexmedetomidine | |
| CN116924980B (en) | A preparation method of milrinone nitrogen oxide | |
| CN110218169B (en) | Synthesis method of chiral 4- (N-benzyloxycarbonyl) pyrrolidone | |
| CN119060034B (en) | A method for preparing pyran-substituted morpholine compounds | |
| CN107488152B (en) | A kind of afatinib intermediate and its synthetic method | |
| CN113912556B (en) | Synthesis method of alpha, beta-dicarbonyl-1, 2, 3-triazole compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20240827 |