CN111100042A - Preparation method of 2-methoxy-5-sulfonamide benzoic acid - Google Patents
Preparation method of 2-methoxy-5-sulfonamide benzoic acid Download PDFInfo
- Publication number
- CN111100042A CN111100042A CN201911125804.3A CN201911125804A CN111100042A CN 111100042 A CN111100042 A CN 111100042A CN 201911125804 A CN201911125804 A CN 201911125804A CN 111100042 A CN111100042 A CN 111100042A
- Authority
- CN
- China
- Prior art keywords
- methoxy
- methoxybenzenesulfonamide
- reaction
- solvent
- temperature
- 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.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of 2-methoxy-5-sulfonamide benzoic acid, which comprises the following steps: carrying out bromination reaction on 4-methoxybenzenesulfonamide and bromine under the action of a reducing agent to obtain 3-bromo-4-methoxybenzenesulfonamide; carrying out substitution reaction on 3-bromo-4-methoxybenzenesulfonamide and cuprous cyanide under the action of a catalyst to generate 3-cyano-4-methoxybenzenesulfonamide; alcoholysis of 3-cyano-4-methoxybenzenesulfonamide with methanol under the catalysis of acid to obtain 2-methoxy-5-sulfonamide methyl benzoate; hydrolyzing the 2-methoxy-5-sulfonamide methyl benzoate under alkaline conditions, and then acidifying to obtain the 2-methoxy-5-sulfonamide benzoic acid. The preparation method of the 2-methoxy-5-sulfonamide benzoic acid has the advantages of mild reaction conditions, simple process and equipment, convenience in operation and environmental friendliness.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a preparation method of 2-methoxy-5-sulfonamide benzoic acid.
Background
Sulpiride belongs to antipsychotic drugs, is a sulfonamide derivative, is a selective antagonist of central dopamine (D2, D3 and D4) receptors, has strong antipsychotic and antiemetic effects and also has a psychostimulant effect. Has good curative effect on symptoms such as apathy, retraction, depression, hallucination, delusion and the like, but has no obvious sedative effect and antimanic effect. Also has good effect of relieving vomit.
2-methoxy-5-sulfonamide benzoic acid is used as a key intermediate of the sulpiride drug, but the synthesis method is not uncommon, foreign technical data (Journal of Medicinal Chemistry, 1989, vol. 32, 4, p. 874-.
On the basis of summarizing relevant working experiences at home and abroad, a new route is provided, the reactions in each step are operated at normal temperature and normal pressure, and equipment is simple to operate. And various raw materials are sold in the market, and a product with higher yield can be obtained through substitution, alcoholysis and hydrolysis reactions, so that the cost is greatly reduced, the reaction selectivity is better improved, the operation steps are simplified, and the method has better theoretical guidance and application prospects.
Disclosure of Invention
The purpose of the invention is as follows: in order to overcome the defects, the invention provides a preparation method of 2-methoxy-5-sulfamide benzoic acid, which has the advantages of mild reaction conditions, simple process and equipment, convenient operation and environmental protection.
The technical scheme is as follows: in order to overcome the defects in the prior art, the invention provides a preparation method of 2-methoxy-5-sulfamide benzoic acid, which comprises the following steps:
(1) adding 4-methoxybenzenesulfonamide, a reducing agent, bromine and a solvent into a reactor, heating to 40-60 ℃ under the condition of stirring, reacting for 2-6 h at the temperature, naturally cooling to room temperature after the reaction is finished, filtering, and evaporating the solvent from the filtrate at normal pressure to obtain a crude product of the 3-bromo-4-methoxybenzenesulfonamide;
(2) adding the 3-bromo-4-methoxybenzenesulfonamide prepared in the step (1), a catalyst, cuprous cyanide and a solvent into a reactor, heating to 120 ℃ under the stirring condition, reacting at the temperature for 6-12 h, naturally cooling to room temperature after the reaction is finished, filtering, evaporating the solvent from the filtrate at normal pressure, pouring the residual liquid into water to separate out a solid, and recrystallizing the filtered filter cake with acetonitrile to obtain the 3-cyano-4-methoxybenzenesulfonamide;
(3) adding the 3-cyano-4-methoxybenzenesulfonamide prepared in the step (2) and methanol into a reactor, uniformly stirring, keeping the temperature of the mixture not to exceed 40 ℃, introducing hydrogen chloride gas to saturation, continuing to react for 4-6 h, adding sodium carbonate powder until no gas is generated after the reaction is finished, filtering, evaporating the filtrate at normal pressure to remove the solvent, and recrystallizing residual liquid through acetonitrile to prepare 2-methoxy-5-sulfonamide methyl benzoate;
(4) adding the 2-methoxy-5-sulfamide methyl benzoate prepared in the step (3) and a sodium hydroxide solution into a reactor, stirring and reacting for 10-20 h, wherein the reaction temperature is not more than 40 ℃, adjusting the pH value to 1 after the reaction is finished, filtering, washing the obtained filter cake with water, drying, and recrystallizing with methanol to obtain the 2-methoxy-5-sulfamide benzoic acid. The room temperature is 20-30 ℃, and the normal pressure is one atmosphere, namely 100 KPa.
Further, the reducing agent in the step (1) is iron powder, and the solvent is dichloromethane.
Further, the weight ratio of the 4-methoxybenzenesulfonamide to the iron powder to the bromine to the dichloromethane is 1: 0.045-0.055:0.428-0.471:4-14.
Further, the solvent in the step (2) is N, N-Dimethylformamide (DMF), and the catalyst is cuprous iodide.
Further, the weight ratio of the 3-bromo-4-methoxybenzenesulfonamide to the cuprous iodide to the cuprous cyanide to the N, N-dimethylformamide is 1: 0.03-0.05:0.338-0.676:4-8.
Further, the weight ratio of the 3-cyano-4-methoxybenzenesulfonamide to the methanol in the step (3) is 1: 10-12.
Further, the mass concentration of the sodium hydroxide in the step (4) is 5%.
Further, the weight ratio of the 3-cyano-4-methoxybenzenesulfonamide to the sodium hydroxide in the step (4) is 1: 8-12.
Further, dilute hydrochloric acid with the mass concentration of 5% is selected for adjusting the pH in the step (4).
Has the advantages that: compared with the prior art, the invention has the following advantages: the preparation method of the 2-methoxy-5-sulfonamide benzoic acid has the advantages of wide source of required raw materials, moderate price, no strong toxicity, environmental friendliness and no harm to the bodies of staff; the reaction conditions are relatively mild, the process is simple, and the reactions in each step are conventional and easy to control; the final product is obtained by alcoholysis hydrolysis method, which effectively improves the selectivity of the reaction.
Drawings
FIG. 1 is a scheme showing the synthesis of 2-methoxy-5-sulfonylbenzoic acids according to the present invention.
Detailed Description
The invention will be further illustrated by the following specific examples, which are given for the purpose of illustration only and are not intended to be limiting. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited. The data given in the examples below include specific operating and reaction conditions and products.
Example 1
A preparation method of 2-methoxy-5-sulfonamide benzoic acid comprises the following steps:
(1) 187 g (1.0 mol) of 4-methoxybenzenesulfonamide, 10.29 g of iron powder, 88 g (1.1 mol) of bromine and 2618 g of dichloromethane are added into a reactor, the temperature is raised to 60 ℃ under the stirring condition, the mixture reacts for 6 hours at the temperature, after the reaction is finished, the mixture is naturally cooled to the room temperature and filtered, and the solvent is removed from the filtrate at normal pressure to obtain 223.44 g of crude 3-bromo-4-methoxybenzenesulfonamide, wherein the yield is 84.0%;
(2) 266 g (1.0 mol) of 3-bromo-4-methoxybenzenesulfonamide prepared in the step (1), 13.3 g of cuprous iodide, 180 g (2.0 mol) of cuprous cyanide and 2128 g of N, N-dimethylformamide are added into a reactor, the temperature is raised to 120 ℃ under the stirring condition, the reaction is carried out for 12 hours at the temperature, the reaction is naturally cooled to room temperature after the reaction is finished, the filtration is carried out, the solvent is evaporated from the filtrate at normal pressure, the residual liquid is poured into water to precipitate solid, the filtered filter cake is recrystallized by acetonitrile to obtain 171.3 g of 3-cyano-4-methoxybenzenesulfonamide, and the yield is 80.8%;
(3) adding 212 g (1.0 mol) of 3-cyano-4-methoxybenzenesulfonamide prepared in the step (2) and 2544 g of methanol into a reactor, uniformly stirring, keeping the temperature of the mixture not more than 40 ℃, introducing hydrogen chloride gas to saturation, continuing to react for 6 hours, adding sodium carbonate powder until no gas is generated after the reaction is finished, filtering, evaporating the solvent from the filtrate at normal pressure, and recrystallizing the residual liquid with acetonitrile to prepare 217.07 g of 2-methoxy-5-sulfonamide methyl benzoate, wherein the yield is 88.6%;
(4) 245 g (1.0 mol) of the 2-methoxy-5-sulfamide methyl benzoate prepared in the step (3) and 2772 g of sodium hydroxide solution with the weight percentage of 5% are added into a reactor, the mixture is stirred and reacted for 20 hours, the reaction temperature is not more than 40 ℃, after the reaction is finished, the pH value is adjusted to 1 by using 5% diluted hydrochloric acid, the mixture is filtered, and the obtained filter cake is washed by water, dried and recrystallized by methanol to prepare 209.06 g of 2-methoxy-5-sulfamide benzoic acid with the yield of 90.5%.
Wherein, the content of the product obtained in the step (1) is 99.27 percent through HPLC detection, the product can be directly used for the next reaction without further purification, and the detection map data after the crude product is sampled and purified by column chromatography are as follows: 1H NMR (CDCl)3,300 MHz)δ:2.86(CH3,s),7.10(CH,m),7.64(CH,m),8.11(CH,m);FAB-MS(m/z):265,267(M+H);
And (3) after the product obtained in the step (2) is purified by column chromatography, the detection map data is as follows: 1H NMR (CDCl)3,300 MHz) δ:3.83(CH3,s),8.19(CH,m),7.39(CH,m),7.98(CH,m);FAB-MS(m/z):213(M+H);
And (3) after the product obtained in the step (3) is purified by column chromatography, the detection map data is as follows: 1H NMR (CDCl)3,300 MHz) δ:3.90(CH3,s),3.95(CH3,s),7.32(CH,m),7.91(CH,m),8.42(CH,m);FAB-MS(m/z):246(M+H);
And (4) after the product obtained in the step (4) is purified by column chromatography, the detection map data is as follows: 1H NMR (CDCl)3,500MHz) δ:3.90(CH3,s),8.58(CH,m),7.42(CH,m),8.04(CH,m), 12.04(OH,m);FAB-MS(m/z):232(M+H)。
Example 2
The other steps are the same as in example 1 except that 3-bromo-4-methoxybenzenesulphonamide of step (1) is prepared as follows:
187 g (1.0 mol) of 4-methoxybenzenesulfonamide, 8.42 g of iron powder, 80 g (1.0 mol) of bromine and 748 g of dichloromethane are added into a reactor, the temperature is raised to 40 ℃ under the stirring condition, the reaction is carried out for 4 hours at the temperature, the crude product of 3-bromo-4-methoxybenzenesulfonamide 198.97 g is prepared after the reaction is finished and the solvent is naturally cooled to room temperature, the filtration is carried out, the filtrate is evaporated at normal pressure, the yield is 74.8%, the content is 99.21% by HPLC, and the product can be directly used for the next reaction without further purification.
Example 3
The other steps are the same as in example 1 except that 3-bromo-4-methoxybenzenesulphonamide in step (1) is prepared as follows:
187 g (1.0 mol) of 4-methoxybenzenesulfonamide, 9.35 g of iron powder, 84 g (1.05 mol) of bromine and 1683 g of dichloromethane are added into a reactor, the temperature is raised to 50 ℃ under the stirring condition, the reaction is carried out for 5 hours at the temperature, the reaction is naturally cooled to the room temperature after the reaction is finished, the filtration is carried out, the filtrate is evaporated at normal pressure to remove the solvent, 206.42 g of crude product of 3-bromo-4-methoxybenzenesulfonamide can be prepared, the yield is 77.6%, the content is 99.13% by HPLC, and the product can be directly used for the next reaction without further purification.
Example 4
The other steps are the same as example 1 except that 3-cyano-4-methoxybenzenesulfonamide in step (2) is prepared as follows:
266 g (1.0 mol) of 3-bromo-4-methoxybenzenesulfonamide prepared in the step (1), 7.98 g of cuprous iodide, 90 g (1.0 mol) of cuprous cyanide and 1064 g of N, N-dimethylformamide are added into a reactor, the temperature is raised to 100 ℃ under the condition of stirring, the reaction is carried out for 6 hours at the temperature, the reaction is naturally cooled to room temperature after the reaction is finished, the filtration is carried out, the solvent is evaporated from the filtrate at normal pressure, the residual liquid is poured into water to precipitate solid, and the filtered filter cake is recrystallized by acetonitrile to obtain 147.34 g of 3-cyano-4-methoxybenzenesulfonamide with the yield of 69.5 percent.
Example 5
The other steps are the same as example 1 except that 3-cyano-4-methoxybenzenesulfonamide in step (2) is prepared as follows:
266 g (1.0 mol) of 3-bromo-4-methoxybenzenesulfonamide prepared in the step (1), 10.64 g of cuprous iodide, 135 g (1.5 mol) of cuprous cyanide and 1596 g of N, N-dimethylformamide are added into a reactor, the temperature is raised to 110 ℃ under the stirring condition, the reaction is carried out for 9 hours at the temperature, the reaction is naturally cooled to room temperature after the reaction is finished, the filtration is carried out, the solvent is evaporated at normal pressure from the filtrate, the residual liquid is poured into water to precipitate solid, the filtered filter cake is recrystallized by acetonitrile to obtain 161.12 g of 3-cyano-4-methoxybenzenesulfonamide, and the yield is 76.0%.
Example 6
The other steps were the same as in example 1 except that methyl 2-methoxy-5-sulfonylbenzoate in step (3) was prepared as follows:
212 g (1.0 mol) of 3-cyano-4-methoxybenzenesulfonamide prepared in the step (2) and 2120 g of methanol are added into a reactor, the mixture is uniformly stirred, the temperature of the mixture is kept to be not more than 40 ℃, hydrogen chloride gas is introduced until the mixture is saturated, the reaction is continued for 4 hours, sodium carbonate powder is added until no gas is generated after the reaction is finished, the filtration is carried out, the solvent is removed from the filtrate at normal pressure, and the residual liquid is recrystallized by acetonitrile to prepare 192.82 g of 2-methoxy-5-sulfonamide methyl benzoate, wherein the yield is 78.7%.
Example 7
The other steps were the same as in example 1 except that methyl 2-methoxy-5-sulfonylbenzoate in step (3) was prepared as follows:
adding 212 g (1.0 mol) of 3-cyano-4-methoxybenzenesulfonamide prepared in the step (2) and 2332 g of methanol into a reactor, uniformly stirring, keeping the temperature of the mixture not more than 40 ℃, introducing hydrogen chloride gas to saturation, continuing to react for 4 hours, adding sodium carbonate powder until no gas is generated after the reaction is finished, filtering, evaporating the solvent from the filtrate at normal pressure, and recrystallizing the residual liquid with acetonitrile to prepare 207.76 g of 2-methoxy-5-sulfonamide methyl benzoate, wherein the yield is 84.8%.
Example 8
The other steps are the same as in example 1 except that 2-methoxy-5-sulfonylbenzoic acid in step (4) is prepared as follows:
245 g (1.0 mol) of the 2-methoxy-5-sulfamide methyl benzoate prepared in the step (3) and 1848 g of 5% sodium hydroxide solution are added into a reactor, the mixture is stirred and reacted for 10 hours, the reaction temperature is not more than 40 ℃, after the reaction is finished, 5% diluted hydrochloric acid is used for adjusting the pH value to 1, the filtration is carried out, and the obtained filter cake is washed by water, dried and recrystallized by methanol to prepare 173.02g of 2-methoxy-5-sulfamide benzoic acid with the yield of 74.9%.
Example 9
The other steps are the same as in example 1 except that 2-methoxy-5-sulfonylbenzoic acid in step (4) is prepared as follows:
245 g (1.0 mol) of the 2-methoxy-5-sulfamide methyl benzoate prepared in the step (3) and 2310 g of 5% sodium hydroxide solution are added into a reactor, the mixture is stirred and reacted for 11 hours, the reaction temperature is not more than 40 ℃, after the reaction is finished, 5% dilute hydrochloric acid is used for adjusting the pH value to 1, the mixture is filtered, and the obtained filter cake is washed by water, dried and recrystallized by methanol to prepare 194.5g of 2-methoxy-5-sulfamide benzoic acid with the yield of 84.2%.
The foregoing is directed to embodiments of the present invention and it is understood by those skilled in the art that various changes may be made without departing from the spirit and scope of the invention.
Claims (9)
1. A preparation method of 2-methoxy-5-sulfonamide benzoic acid is characterized by comprising the following steps: the method comprises the following steps:
(1) adding 4-methoxybenzenesulfonamide, a reducing agent, bromine and a solvent into a reactor, heating to 40-60 ℃ under the condition of stirring, reacting for 2-6 h at the temperature, naturally cooling to room temperature after the reaction is finished, filtering, and evaporating the solvent from the filtrate at normal pressure to obtain a crude product of the 3-bromo-4-methoxybenzenesulfonamide;
(2) adding the 3-bromo-4-methoxybenzenesulfonamide prepared in the step (1), a catalyst, cuprous cyanide and a solvent into a reactor, heating to 120 ℃ under the stirring condition, reacting at the temperature for 6-12 h, naturally cooling to room temperature after the reaction is finished, filtering, evaporating the solvent from the filtrate at normal pressure, pouring the residual liquid into water to separate out a solid, and recrystallizing the filtered filter cake with acetonitrile to obtain the 3-cyano-4-methoxybenzenesulfonamide;
(3) adding the 3-cyano-4-methoxybenzenesulfonamide prepared in the step (2) and methanol into a reactor, uniformly stirring, keeping the temperature of the mixture not to exceed 40 ℃, introducing hydrogen chloride gas to saturation, continuing to react for 4-6 h, adding sodium carbonate powder until no gas is generated after the reaction is finished, filtering, evaporating the filtrate at normal pressure to remove the solvent, and recrystallizing residual liquid through acetonitrile to prepare 2-methoxy-5-sulfonamide methyl benzoate;
(4) adding the 2-methoxy-5-sulfamide methyl benzoate prepared in the step (3) and a sodium hydroxide solution into a reactor, stirring and reacting for 10-20 h, wherein the reaction temperature is not more than 40 ℃, adjusting the pH value to 1 after the reaction is finished, filtering, washing the obtained filter cake with water, drying, and recrystallizing with methanol to obtain the 2-methoxy-5-sulfamide benzoic acid.
2. The process for preparing 2-methoxy-5-sulfonylbenzoic acid, according to claim 1, wherein: the reducing agent in the step (1) is iron powder, and the solvent is dichloromethane.
3. The process for producing 2-methoxy-5-sulfonylbenzoic acid according to claim 2, wherein: the weight ratio of the 4-methoxybenzenesulfonamide to the iron powder to the bromine to the dichloromethane is 1: 0.045-0.055:0.428-0.471:4-14.
4. The process for preparing 2-methoxy-5-sulfonylbenzoic acid according to claim 1, wherein: the solvent in the step (2) is N, N-dimethylformamide, and the catalyst is cuprous iodide.
5. The process for producing 2-methoxy-5-sulfonylbenzoic acid according to claim 4, wherein: the weight ratio of the 3-bromo-4-methoxybenzenesulfonamide to the cuprous iodide to the cuprous cyanide to the N, N-dimethylformamide is 1: 0.03-0.05:0.338-0.676:4-8.
6. The process for producing 2-methoxy-5-sulfonylbenzoic acid according to claim 1, wherein: the weight ratio of the 3-cyano-4-methoxybenzenesulfonamide to the methanol in the step (3) is 1: 10-12.
7. The process for producing 2-methoxy-5-sulfonylbenzoic acid according to claim 1, wherein: the mass concentration of the sodium hydroxide in the step (4) is 5%.
8. The process for producing 2-methoxy-5-sulfonylbenzoic acid according to claim 7, wherein: the weight ratio of the 3-cyano-4-methoxybenzenesulfonamide to the sodium hydroxide in the step (4) is 1: 8-12.
9. The process for producing 2-methoxy-5-sulfonylbenzoic acid according to claim 8, wherein: and (4) adjusting the pH value, and selecting dilute hydrochloric acid with the mass concentration of 5%.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911125804.3A CN111100042B (en) | 2019-11-18 | 2019-11-18 | Preparation method of 2-methoxy-5-sulfonamide benzoic acid |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911125804.3A CN111100042B (en) | 2019-11-18 | 2019-11-18 | Preparation method of 2-methoxy-5-sulfonamide benzoic acid |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111100042A true CN111100042A (en) | 2020-05-05 |
CN111100042B CN111100042B (en) | 2022-05-31 |
Family
ID=70420749
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911125804.3A Active CN111100042B (en) | 2019-11-18 | 2019-11-18 | Preparation method of 2-methoxy-5-sulfonamide benzoic acid |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111100042B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113621098A (en) * | 2020-05-09 | 2021-11-09 | 中国石油天然气股份有限公司 | Propylene polymerization catalyst, propylene polymerization catalyst system, preparation and application thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1293665A (en) * | 1998-02-18 | 2001-05-02 | 神经研究公司 | New compounds and their use as positive AMPA receptor modulators |
US20060199817A1 (en) * | 2005-03-03 | 2006-09-07 | Amgen Inc. | Phthalazine, aza- and diaza-phthalazine compounds and methods of use |
US20190119203A1 (en) * | 2016-04-18 | 2019-04-25 | IFM Tre, Inc. | Compounds and compositions for treating conditions associated with nlrp activity |
-
2019
- 2019-11-18 CN CN201911125804.3A patent/CN111100042B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1293665A (en) * | 1998-02-18 | 2001-05-02 | 神经研究公司 | New compounds and their use as positive AMPA receptor modulators |
US20060199817A1 (en) * | 2005-03-03 | 2006-09-07 | Amgen Inc. | Phthalazine, aza- and diaza-phthalazine compounds and methods of use |
US20190119203A1 (en) * | 2016-04-18 | 2019-04-25 | IFM Tre, Inc. | Compounds and compositions for treating conditions associated with nlrp activity |
Non-Patent Citations (2)
Title |
---|
MARC W. HARROLD ET AL.: "Synthesis and D2 Dopaminergic Activity of Pyrrolidinium, Tetrahydrothiophenium, and Tetrahydrothiophene Analogues of Sulpiride", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
V.A.SMIRNOV ET AL.: "SYNTHESIS AND DIURETIC ACTIVITY OF 3-NITRO(AMINO)-4-CHLORO-5-SULFAMOYLSALICYLIC ACIDS AND THEIR DERIVATIVES", 《PHARMACEUTICAL CHEMISTRY JOURNAL》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113621098A (en) * | 2020-05-09 | 2021-11-09 | 中国石油天然气股份有限公司 | Propylene polymerization catalyst, propylene polymerization catalyst system, preparation and application thereof |
CN113621098B (en) * | 2020-05-09 | 2022-11-04 | 中国石油天然气股份有限公司 | Propylene polymerization catalyst, propylene polymerization catalyst system, preparation and application thereof |
Also Published As
Publication number | Publication date |
---|---|
CN111100042B (en) | 2022-05-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110950765B (en) | Preparation method of terbutaline sulfate | |
EP3828170A1 (en) | Method for safely preparing pimavanserin and tartrate salt thereof using triphosgene | |
CN105884628B (en) | The preparation method of 2,4- di-t-butyl -5- amino phenols | |
CN101486753A (en) | Novel method for synthesizing finasteroid | |
CN114539048B (en) | Carlong anhydride intermediate and preparation method of Carlong anhydride | |
CN110183445A (en) | The synthetic method of Moxifloxacin and its derivative | |
CN111100042B (en) | Preparation method of 2-methoxy-5-sulfonamide benzoic acid | |
CN104844593A (en) | Synthetic method for Apixaban drug intermediate | |
CN112552224A (en) | Synthesis method of 4-hydroxyindole | |
CN113698317A (en) | Synthetic method of apatamide, intermediate and synthetic method thereof | |
CN111793016A (en) | Preparation method of larotinib intermediate and intermediate compound | |
CN115340481A (en) | Method for industrially producing deuterated medical intermediate by adopting immobilized nickel catalysis | |
CN112250586A (en) | Preparation method of terbutaline sulfate and B crystal form thereof | |
CN108409561B (en) | Preparation method of 5-aminolevulinic acid hydrochloride and intermediate | |
CN114516817A (en) | Chemical intermediate and preparation method thereof | |
CN108947919A (en) | A kind of novel processing step and its key intermediate of gout suppressant Lesinurad | |
CN106957235B (en) | A kind of preparation method of tamoxifen | |
CN112479993A (en) | Synthetic method applied to KRAS inhibitor drug heterocyclic intermediate | |
CN110229096B (en) | Preparation method of 2, 6-pyridinedicarboxylic acid | |
CN111499528A (en) | Terbutaline sulfate intermediate, preparation method thereof and method for preparing terbutaline sulfate by using terbutaline sulfate intermediate | |
US20220235010A1 (en) | Synthesis method for 1-methyl-1h-indazole-6-carboxylic acid | |
CN114437007A (en) | Preparation method of prucalopride intermediate | |
CN112209841B (en) | Synthesis method of terbutaline and application of terbutaline in preparation of terbutaline sulfate | |
CN113045475A (en) | Preparation method of 5-bromo-7-methylindole | |
CN111100062A (en) | Synthesis method of donepezil hydrochloride |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |