CN117304067A - Synthesis method of non-nefardone intermediate 4-cyano-2-methoxybenzaldehyde - Google Patents
Synthesis method of non-nefardone intermediate 4-cyano-2-methoxybenzaldehyde Download PDFInfo
- Publication number
- CN117304067A CN117304067A CN202210707956.XA CN202210707956A CN117304067A CN 117304067 A CN117304067 A CN 117304067A CN 202210707956 A CN202210707956 A CN 202210707956A CN 117304067 A CN117304067 A CN 117304067A
- Authority
- CN
- China
- Prior art keywords
- methoxybenzaldehyde
- bromo
- cyano
- reaction
- steps
- 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
- ZXENVSJZOHXCKL-UHFFFAOYSA-N 4-formyl-3-methoxybenzonitrile Chemical compound COC1=CC(C#N)=CC=C1C=O ZXENVSJZOHXCKL-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000001308 synthesis method Methods 0.000 title claims description 4
- YMXQYZABFWVXEK-UHFFFAOYSA-N 4-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC(Br)=CC=C1C=O YMXQYZABFWVXEK-UHFFFAOYSA-N 0.000 claims abstract description 20
- HXTWKHXDFATMSP-UHFFFAOYSA-N 4-bromo-2-hydroxybenzaldehyde Chemical compound OC1=CC(Br)=CC=C1C=O HXTWKHXDFATMSP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 6
- AWDBHOZBRXWRKS-UHFFFAOYSA-N tetrapotassium;iron(6+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+6].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] AWDBHOZBRXWRKS-UHFFFAOYSA-N 0.000 claims abstract description 6
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims abstract description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 238000010438 heat treatment Methods 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 238000006257 total synthesis reaction Methods 0.000 claims description 2
- 238000007039 two-step reaction Methods 0.000 claims description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 abstract description 4
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 238000007333 cyanation reaction Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- FYAKLZKQJDBBKW-UHFFFAOYSA-N 4-bromo-2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1O FYAKLZKQJDBBKW-UHFFFAOYSA-N 0.000 description 4
- BTBHLEZXCOBLCY-QGZVFWFLSA-N (4s)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide Chemical compound C1([C@@H]2C(=C(C)NC=3C(C)=CN=C(C2=3)OCC)C(N)=O)=CC=C(C#N)C=C1OC BTBHLEZXCOBLCY-QGZVFWFLSA-N 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 208000020832 chronic kidney disease Diseases 0.000 description 3
- 229950004408 finerenone Drugs 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229940083712 aldosterone antagonist Drugs 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 description 1
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- WPGAGRPPDYAZAD-UHFFFAOYSA-N methyl 4-bromo-2-methoxybenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1OC WPGAGRPPDYAZAD-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
- C07C253/34—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of medical synthesis, and relates to a novel method for synthesizing a compound non-nelidone intermediate 4-cyano-2-methoxybenzaldehyde. The method comprises the following steps: (1) The 4-bromo-2-hydroxybenzaldehyde and dimethyl sulfate are alkylated for one time under the action of potassium carbonate to generate 4-bromo-2-methoxybenzaldehyde; (2) 4-bromo-2-methoxybenzaldehyde is subjected to cyanation reaction under the action of potassium hexacyanoferrate, sodium carbonate and palladium acetate to generate a target product. The method has the advantages of simple steps, simple operation, high efficiency, green and economic performance and suitability for industrial production.
Description
Technical Field
The invention belongs to the field of medical synthesis, and relates to a novel method for synthesizing a compound non-nelidone intermediate 4-cyano-2-methoxybenzaldehyde.
Background
The chemical structure of the 4-cyano-2-methoxybenzaldehyde is shown in the following formula:
non-nerenone (Finerenone) is a novel non-steroidal Mineralocorticoid Receptor Antagonist (MRA), has high selectivity for mineralocorticoid receptors, and low affinity for androgens, progestogens, estrogens, and glucocorticoid receptors, and these properties allow Finerenone to achieve target therapeutic effects while minimizing the incidence of adverse events. Moreover, finerenone has a uniform tissue distribution between the heart and kidneys, which properties make it more advantageous for high-risk populations with Chronic Kidney Disease (CKD) combined with cardiovascular complications.
Although 4-cyano-2-methoxybenzaldehyde is commercialized, it is expensive and not available in large quantities.
CN 108137587B is a domestic patent application directed to a class of pharmaceutical compounds, non-nerlidone, which are effective in reducing protein urea in short-term trials in chronic kidney disease and type 2 diabetics. Whereas 4-cyano-2-methoxybenzaldehyde is an intermediate in the synthetic route of non-nelidone, CN 108137587B reports its synthetic route:
the route takes 4-bromo-2-hydroxybenzoic acid (IV) and dimethyl sulfate (II-a) as starting materials, and under the heating condition, 4-bromo-2-methoxybenzoic acid methyl ester (V) is obtained by the reaction of auxiliary alkali potassium carbonate in acetone; the compound (V) is refluxed at low temperature in a toluene system, and reduced by red aluminum and 1-methylpiperazine to obtain 4-bromo-2-methoxybenzaldehyde (III); the compound (III) is subjected to cyanation in a palladium acetate system to obtain a target product 4-cyano-2-methoxybenzaldehyde (I). Although the process has reduced the synthesis steps to three steps, the four-step synthesis route from 4-hydroxy-3-methoxybenzene glycol was improved (Chem Med Chem 2012,7, 1385). However, the 1-methylpiperazine used in the route has a certain irritation to eyes, skin and upper respiratory tract, is a flammable liquid, and is required to be stored in a dry and ventilated warehouse in a sealed manner, and is far away from fire sources, strong oxidation and strong acidic substances. Red aluminum is active and flammable in nature and sensitive to water and air.
Disclosure of Invention
The invention designs a totally new route for synthesizing the 4-cyano-2-methoxybenzaldehyde, which has the advantages of simple steps, simple operation, high efficiency, green and economic performance and suitability for industrial production.
The synthesis method of the 4-cyano-2-methoxybenzaldehyde comprises the following steps:
(1) Adding 4-bromo-2-hydroxybenzaldehyde (II) into a reaction bottle, adding anhydrous acetone under a nitrogen environment, and stirring at room temperature for 15min; adding dimethyl sulfate (II-a), heating to 60-90 ℃, and carrying out reflux heating reaction to obtain 4-bromo-2-methoxybenzaldehyde (III), wherein the reaction equation is as follows:
(2) Putting the compound (III) into a reaction bottle containing DMF, then putting potassium hexacyanoferrate, sodium carbonate and palladium acetate, heating to 120 ℃ for reaction to obtain a target product (I), wherein the reaction equation is as follows:
in the method for preparing the 4-cyano-2-methoxybenzaldehyde, 4-bromo-2-hydroxybenzaldehyde (II) is used as a starting material for a two-step reaction in the step (1), and the target product (I) is prepared.
In the method for preparing the 4-cyano-2-methoxybenzaldehyde, the molar ratio of the 4-bromo-2-hydroxybenzaldehyde (II), the acetone to the ester (II-a) in the step (1) is 1:1.5:1.5.
In the method for preparing the 4-cyano-2-methoxybenzaldehyde, the temperature is heated to 60-90 ℃ in the step (1) for reaction, and the temperature is preferably 60 ℃.
The method for preparing the 4-cyano-2-methoxybenzaldehyde comprises the following steps that in the step (2), the dosage of the 4-bromo-2-methoxybenzaldehyde (III) is 1eq; the potassium hexacyanoferrate is used in an amount of 0 to 0.5eq, preferably 0.22eq; the amount of sodium carbonate is 1 to 2eq, preferably 1eq.
The method for preparing the 4-cyano-2-methoxybenzaldehyde comprises the steps of (1) and (2), wherein the total synthesis steps are two, 4-bromo-2-hydroxybenzaldehyde (II) is taken as a starting material to prepare a target product (I), and the preparation steps are simplified.
Compared with the prior art, the invention has the following beneficial effects:
(1) A novel process for preparing 4-cyano-2-methoxybenzaldehyde is provided.
(2) The 4-bromo-2-methoxybenzaldehyde (III) is prepared from the easily available 4-bromo-2-hydroxybenzaldehyde (II) and is used as a reaction intermediate, so that the purchase cost is greatly reduced.
(3) The synthesis step of the 4-bromo-2-methoxybenzaldehyde (III) is simplified, and the 4-bromo-2-hydroxybenzoic acid (IV) is prepared by two steps, and the 4-bromo-2-hydroxybenzaldehyde (II) is prepared by one step. The obtained product has high yield and purity.
Compared with the prior art CN 108137587B, the method further reduces the steps, avoids the use of 1-methylpiperazine and red aluminum, reduces the post-treatment operation and the generation of three wastes, can reduce the loss and improve the yield.
Detailed Description
The advantages of the invention will now be further described by the following examples, which are given for illustrative purposes only and do not limit the scope of the invention, while variations and modifications apparent to those skilled in the art in light of the present disclosure are included within the scope of the invention.
Example 1:
preparation of compound (III): 4-bromo-2-hydroxybenzaldehyde (1.02 g,5.08 mmol) and potassium carbonate (1.0523 g,7.62 mmol) were charged to a 50mL two-necked round bottom flask; adding a plug for sealing, filling and replacing N2, and then adding 10mL of anhydrous acetone (dried by a molecular sieve); stirring for 15min; dimethyl sulfate (721. Mu.L, 7.62 mmol) was added. Then heating to 60 ℃ and starting reflux heating for 2h. After the reaction was completed, the reaction mixture mother liquor was suction filtered into a single-neck round bottom flask, and after suction filtration, washed with 2ml of acetone x 3. Removing acetone by rotary evaporator, andadding 10mL of CH 2 Cl 2 In a single neck round bottom flask and stirred for 5min. Subsequently transferred to a separatory funnel and extracted with 10mL of water and 10mL of saline solution was added, followed by CH 2 Cl 2 20mL of 3 extract aqueous phase, combined organic layers with Na 2 SO 4 Dried and CH was removed by rotary evaporator 2 Cl 2 The corresponding methyl ether product was obtained as a white solid (1.0711 g, 98%).
Example 2:
preparation of compound (III): 4-bromo-2-hydroxybenzaldehyde (1.02 g,5.08 mmol) and potassium carbonate (1.0523 g,7.62 mmol) were charged to a 50mL two-necked round bottom flask; adding a plug for sealing, filling and replacing N2, and then adding 10mL of anhydrous acetone (dried by a molecular sieve); stirring for 15min; dimethyl sulfate (721. Mu.L, 7.62 mmol) was added. Then heating to 90 ℃ and starting reflux heating for 2h. After the reaction was completed, the reaction mixture mother liquor was suction filtered into a single-neck round bottom flask, and after suction filtration, washed with 2ml of acetone x 3. The acetone was then removed by rotary evaporation followed by addition of 10mL CH 2 Cl 2 In a single neck round bottom flask and stirred for 5min. Subsequently transferred to a separatory funnel and extracted with 10mL of water and 10mL of saline solution was added, followed by CH 2 Cl 2 20mL of 3 extract aqueous phase, combined organic layers with Na 2 SO 4 Dried and CH was removed by rotary evaporator 2 Cl 2 The corresponding methyl ether product was obtained as a white solid (1.0815 g, 99%).
Example 3:
preparation of 4-cyano-2-methoxybenzaldehyde: 4-bromo-2-methoxybenzaldehyde (1.26 g,5.86 mmol) was first put into DMF (10 mL), then 0.22 equivalent of potassium hexacyanoferrate (475.2 mg,1.29 mmol) and 1 equivalent of sodium carbonate (621.1 mg,5.86 mmol) were put into the mixture, and then 0.005 equivalent of palladium acetate (6.6 mg,0.0293 mmol) was added. Heated to 120℃for 4 hours. After the reaction was completed, the solution was cooled to room temperature, and then water and ethyl acetate were added. The ethyl acetate phase was separated off and the aqueous phase was again washed with ethyl acetate, and the combined ethyl acetate phases were distilled in isopropanol. The product was precipitated by water precipitation at boiling temperature (siegehitze). After isolation, the product was dried under vacuum (0.7552 g, 80%).
Claims (6)
1. The synthesis method of the non-nefarone intermediate 4-cyano-2-methoxybenzaldehyde is characterized by comprising the following steps of:
(1) Adding 4-bromo-2-hydroxybenzaldehyde (II) into a reaction bottle, adding anhydrous acetone under a nitrogen environment, and stirring at room temperature for 15min; adding dimethyl sulfate (II-a), heating to 60-90 ℃, and carrying out reflux heating reaction to obtain 4-bromo-2-methoxybenzaldehyde (III), wherein the reaction equation is as follows:
(2) Putting the compound (III) into a reaction bottle containing DMF, then putting potassium hexacyanoferrate, sodium carbonate and palladium acetate, heating to 120 ℃ for reaction to obtain a target product (I), wherein the reaction equation is as follows:
2. the process for preparing 4-cyano-2-methoxybenzaldehyde as claimed in claim 1, wherein 4-bromo-2-hydroxybenzaldehyde (II) is used as a starting material for the two-step reaction in step (1) to give the desired product (I).
3. The method for preparing 4-cyano-2-methoxybenzaldehyde according to claim 1, wherein the molar ratio of 4-bromo-2-hydroxybenzaldehyde (II), acetone to ester (II-a) in step (1) is 1:1.5:1.5.
4. A process for the preparation of 4-cyano-2-methoxybenzaldehyde as claimed in claim 1, wherein in step (1) the reaction is carried out by heating to 60 ℃ to 90 ℃, preferably 60 ℃.
5. A process for preparing 4-cyano-2-methoxybenzaldehyde according to claim 1, wherein in step (2) 4-bromo-2-methoxybenzaldehyde (III) is used in an amount of 1eq; the potassium hexacyanoferrate is used in an amount of 0 to 0.5eq, preferably 0.22eq; the amount of sodium carbonate is 1 to 2eq, preferably 1eq.
6. The method for preparing 4-cyano-2-methoxybenzaldehyde according to claim 1, wherein the total synthesis steps of steps (1) and (2) are two steps, and 4-bromo-2-hydroxybenzaldehyde (II) is used as a starting material to prepare the target product (I), thereby simplifying the preparation steps.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210707956.XA CN117304067A (en) | 2022-06-21 | 2022-06-21 | Synthesis method of non-nefardone intermediate 4-cyano-2-methoxybenzaldehyde |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210707956.XA CN117304067A (en) | 2022-06-21 | 2022-06-21 | Synthesis method of non-nefardone intermediate 4-cyano-2-methoxybenzaldehyde |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117304067A true CN117304067A (en) | 2023-12-29 |
Family
ID=89235881
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210707956.XA Pending CN117304067A (en) | 2022-06-21 | 2022-06-21 | Synthesis method of non-nefardone intermediate 4-cyano-2-methoxybenzaldehyde |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117304067A (en) |
-
2022
- 2022-06-21 CN CN202210707956.XA patent/CN117304067A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104844593A (en) | Synthetic method for Apixaban drug intermediate | |
| CN117304067A (en) | Synthesis method of non-nefardone intermediate 4-cyano-2-methoxybenzaldehyde | |
| CN115197150B (en) | Preparation method of L-carnosine | |
| CN111004205A (en) | Synthetic method for preparing piperonyl butoxide under catalysis of composite alkali | |
| CN110872251A (en) | N-ethylpyridine methylamine trifluoroacetate and crystal, preparation process and application thereof | |
| CN103508934A (en) | Preparation method of gliclazide | |
| CN108948117B (en) | Synthetic method of obeticholic acid | |
| CN112479967B (en) | Biliverdin compound, and preparation method and application thereof | |
| CN104326927B (en) | A kind of preparation method of 1-[2-amino-1-(4-methoxyphenyl) ethyl] Hexalin sulfate | |
| CN111454315B (en) | Synthesis method of androstane-16-alkene-3 beta-alcohol | |
| CN111100042B (en) | Preparation method of 2-methoxy-5-sulfonamide benzoic acid | |
| CN108084077B (en) | Synthetic method of zafirlukast intermediate | |
| CN115124473B (en) | Method for synthesizing cimetidine related substance B | |
| CN106542961B (en) | A kind of synthetic method of racecadotril intermediate | |
| CN103476763B (en) | 3,5-dioxo capronate is prepared with two steps | |
| CN115919817B (en) | Gem diselenide compound and its synthesis method and application | |
| CN103910704B (en) | A kind of Preparation Method And Their Intermediate compound of nebivolol | |
| CN115490701B (en) | Method for synthesizing cantharidin | |
| CN113105384B (en) | Preparation method of carbazole and fluorene organic electroluminescent intermediate | |
| CN108727345B (en) | Preparation method of imidazole ring intermediate | |
| CN102276487B (en) | Preparation method of trimebutine | |
| CN109111371B (en) | Preparation method of hydrazino ethyl acetate hydrochloride | |
| CN108774279B (en) | Synthesis method of 6-hydroxymethyl-17 alpha-acetoxyl-19-norpregna-4, 6-diene-3, 20-diketone | |
| CN109053534A (en) | A kind of preparation method of medicine intermediate 4- nitroindoline | |
| CN104370807B (en) | The synthetic method of a kind of 6-hydroxyl-5-nitronicotinic acid and process for separation and purification thereof |
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 |