WO2023229322A1 - Procédé de préparation de dérivés de 6-méthoxypyridin-3-yl - Google Patents

Procédé de préparation de dérivés de 6-méthoxypyridin-3-yl Download PDF

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Publication number
WO2023229322A1
WO2023229322A1 PCT/KR2023/006926 KR2023006926W WO2023229322A1 WO 2023229322 A1 WO2023229322 A1 WO 2023229322A1 KR 2023006926 W KR2023006926 W KR 2023006926W WO 2023229322 A1 WO2023229322 A1 WO 2023229322A1
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formula
compound represented
acid
sodium
reaction
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PCT/KR2023/006926
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English (en)
Korean (ko)
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서한나
이재홍
이건희
이형준
이지권
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일동제약(주)
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Priority claimed from KR1020230010923A external-priority patent/KR20230163283A/ko
Application filed by 일동제약(주) filed Critical 일동제약(주)
Publication of WO2023229322A1 publication Critical patent/WO2023229322A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a process for preparing 6-methoxypyridin-3-yl derivatives.
  • Potassium-competitive acid blocker is attracting attention to improve the shortcomings of proton pump inhibitor (PPI).
  • PPI proton pump inhibitor
  • Potassium-competitive gastric acid secretion inhibitors strongly and rapidly inhibit gastric acid secretion by reversibly and competitively binding with K + ions to the proton pump (H + /K + -ATPase), an enzyme involved in the final stage of gastric acid secretion in gastric wall cells.
  • PPI proton pump inhibitor
  • PPI proton pump inhibitor
  • P-CAB preparations show pharmacological activity that maintains pharmacological activity even when pH increases, and some related side effects have been reported.
  • P-CAB agents are mainly metabolized through the CYP3A4 enzyme, the differences in drug efficacy between individuals are relatively small, and concerns about interactions with drugs metabolized by the CYP2C19 enzyme are relatively low.
  • vonoprazan was confirmed to cause more severe hypergastrinemia than lansoprazole, a conventional PPI drug.
  • This hypergastrinemia may include enterochromaffin-like (ECL)-cell hyperplasia; parietal cell hyperplasia; fundic gland polyp; It can cause problems such as bone loss, damaged bone quality, and fractures.
  • ECL enterochromaffin-like
  • Verietal cell hyperplasia parietal cell hyperplasia
  • fundic gland polyp It can cause problems such as bone loss, damaged bone quality, and fractures.
  • vonoprazan has been reported to be associated with the development of gastric neuroendocrine cell tumors in mouse and rat carcinogenicity tests.
  • discontinuation of P-CAB or PPI drugs such as vonoprazan restores excessive stomach acid and causes indigestion, so despite the above problems, drug administration cannot be easily stopped.
  • Korean Patent Registration No. 10-2432523 discloses a novel P-CAB inhibitor showing excellent acid secretion inhibition effect.
  • Korean Patent Registration No. 10-2432523 includes the steps (I) of introducing an appropriate heteroarylsulfonyl group into the starting material using a base in the presence of an inert solvent; Step (II) reduction using a reducing agent in the presence of an inert solvent; Step (III) oxidation using an oxidizing agent in the presence of an inert solvent; and step (IV), which is a reductive amination process using an appropriate amine and reducing agent, to prepare a new P-CAB drug.
  • the manufacturing methods disclosed in the above patent have the disadvantage that the manufacturing process is very long and the production yield is low.
  • the manufacturing process is risky using materials such as DIBAL, and as a raw material with a high unit cost, sulfone derivatives are used in the early stages of the reaction, making it unsuitable for mass production, and it has the disadvantage of making subsequent development difficult with salts.
  • the present inventors developed a new manufacturing process that greatly increased the production level of the target material while maximizing the yield during the manufacturing process, and completed the present invention.
  • the present invention is intended to provide a method for producing 6-methoxypyridin-3-yl derivatives.
  • a compound represented by the following formula (1) is prepared including steps 1 and 2 below.
  • a method is provided that can produce a compound represented by the following formula 1-1, further including step 3:
  • Step 1 is a step of preparing a compound represented by Formula 4 by reacting the compound represented by Formula 2 with the compound represented by Formula 3, wherein the pyrrole group of the compound represented by Formula 2 is substituted This is the stage of introducing the dil sulphone diary.
  • the reaction of step 1 may be performed in the presence of 4-(dimethylamino)-pyridine, a base, and an organic solvent.
  • the bases include N,N -diisopropylethylamine, triethylamine, diisopropylamine, diisopropylethylamine, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, and hydroxide.
  • Lithium, sodium methylate, potassium butyrate, cesium carbonate, or a mixture of two or more of these can be used, and specifically, triethylamine can be used.
  • any solvent favorable for dispersion of the base and 4-(dimethylamino)-pyridine may be used, such as acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl ether, methyl t-butyl ether, toluene, xyl Ren, heptane, or a mixture of two or more thereof may be used as the reaction solvent.
  • acetone may be used as the reaction solvent in step 1.
  • the reaction yield can be maximized by facilitating precipitation of bases, such as triethylamine, under the above solvent.
  • the molar ratio of the compound represented by Formula 2 and the compound represented by Formula 3 may be 10:1 to 1:10, specifically 5:1 to 1:5, and more specifically, It may be 3:1 to 1:3.
  • the reaction of step 1 may be performed at 10 to 35 °C. Specifically, the reaction within the reaction temperature range of Step 1 can contribute to increasing the conversion rate of Step 1 and reducing the content of related substances in the final material.
  • the reaction in step 1 may be performed for 30 minutes to 8 hours. If the reaction time is less than 30 minutes, the reaction does not proceed sufficiently and the production yield is lowered, and if the reaction time exceeds 8 hours, the production yield does not substantially increase. More specifically, the reaction may be performed for 1 hour to 5 hours.
  • a step of purifying the compound represented by Formula 4 may be further included after the reaction is completed. Specifically, it may be performed by crystallizing the compound represented by Formula 4 from the reaction product of Step 1.
  • an alcohol having 1 to 4 carbon atoms can be used as a solvent for crystallizing the compound represented by Formula 4 from the reaction product.
  • the alcohol having 1 to 4 carbon atoms may be methanol, ethanol, propanol, 2-propanol, butanol, tert-butanol, or a mixture of two or more thereof. More specifically, 2-propanol may be used alone. For example, 2-propanol may be added to raise the temperature to 40 to 80°C, cooled to 15 to 35°C, and then stirred. If necessary, stirring may be performed by additional cooling to 0 to 10°C. This process can be effective in removing bases in residual solvents, such as triethylamine and 4-(dimethylamino)-pyridine.
  • the water content contained in the compound represented by Formula 4 can be reduced by drying at 40 to 60° C. for 10 to 14 hours. Through this, the moisture content of the compound represented by Formula 4 can be significantly lowered, thereby increasing the conversion rate in the next step.
  • a washing step using a solvent used after completion of the reaction in each step may be further included.
  • Step 2 is a step of reacting the compound represented by Formula 4 with methylamine to produce an intermediate and adding a reducing agent to convert the intermediate into the compound represented by Formula 1.
  • Step 2 is a step of converting the compound represented by Formula 4 into the compound represented by Formula 1 using a reductive amination reaction.
  • Step 2 the compound represented by Formula 4 produces an imine compound through an imine production reaction with methylamine, and since this imine compound corresponds to an intermediate of an unstable structure, it undergoes a reduction reaction to obtain the formula It can be easily converted to the compound represented by 1.
  • the reductive imination reaction of step 2 may be performed in a reaction solvent that is water, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, tetrahydrofuran, ethyl acetate, dimethyl ether, acetonitrile, or a mixture of two or more thereof.
  • a reaction solvent that is water, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, tetrahydrofuran, ethyl acetate, dimethyl ether, acetonitrile, or a mixture of two or more thereof.
  • the solvent conditions according to the present invention use a solvent that can provide a reaction under mild conditions, and in particular, it has the advantage of being a reaction under solvent conditions that do not cause problems under regulations such as the Ministry of Food and Drug Safety.
  • the compound represented by Formula 4 and the methylamine are added together with the reaction solvent, and then stirred at 15 to 35 ° C., more preferably 20 to 30 ° C. for 20 minutes to 2 hours, to obtain Formula 4
  • the compound represented by and the methylamine may react while sufficiently dissolved in the solvent to produce an imine compound.
  • the methylamine may preferably be methylamine dissolved in water.
  • the above reaction conditions have the advantage of being a reaction under mild conditions close to room temperature conditions compared to previously known conditions.
  • it has the advantage of minimizing the content of related substances by appropriately controlling the equivalent weight of methylamine. For example, adding it in an equivalent amount of 1.5 to 2.5 eq has the advantage of minimizing the production of related substances related to dimer formation compared to previously known methods.
  • the reduction reaction of the intermediate (i.e., imine compound) produced by the reaction between the compound represented by Formula 4 and methylamine can proceed more stably at low temperatures.
  • the reactor temperature is cooled until it reaches the range of -5 to 15 °C, for example, 0 °C to 10 °C, and then the cooled
  • the reducing agent can be added while observing the temperature range and then stirred while maintaining the reactor temperature.
  • the intermediate i.e., imine compound
  • the intermediate can stably react with the reducing agent and be converted into the compound represented by Formula 1.
  • the reducing agent may be any one or more selected from the group consisting of sodium borohydride, sodium cyanoborohydride, and sodium triacetoxyborohydride.
  • the molar ratio of the compound represented by Formula 4 and the methylamine may be 10:1 to 1:10, and the molar ratio of the compound represented by Formula 4 and the reducing agent may be 10:1 to 1:10. Specifically, each molar ratio may be 5:1 to 1:5, and more specifically, 3:1 to 1:3.
  • Organic solvents that are a mixture of two or more may be used.
  • Ethyl acetate may be preferably used.
  • step 2 the following step 3 may optionally be further included.
  • This three-step process may proceed through the following steps:
  • a production method further comprising:
  • Step 3 in order to supply the compound represented by Formula 1 in the form of a pharmaceutically acceptable salt, an acid is added to the compound represented by Formula 1 simultaneously with or after Step 2, to obtain Formula 1-1. This is the step of obtaining an indicated and pharmaceutically acceptable acid salt.
  • step 3 involves supplying an organic solvent to the compound represented by Formula 1 and then supplying an acid or a mixed solution thereof with an organic solvent to crystallize the acid salt represented by Formula 1-1. May include steps.
  • an organic solvent may be supplied to the concentrated residue containing the compound represented by Formula 1 above.
  • the organic solvent supplied at this time is ethyl acetate, diethyl ether, dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, acetone, methyl ethyl ketone, methyl isobutyl ketone, methanol, ethanol, isopropyl alcohol, acetonitrile, and dichloro. It may be methane, normal hexane, dimethyl sulfoxide, or a mixture of two or more of these.
  • a mixed solvent of ethanol and ethyl acetate Preferably, a mixed solvent of ethanol and ethyl acetate; Mixed solvent of isopropyl alcohol and ethyl acetate, mixed solvent of methanol and ethyl acetate, mixed solvent of methanol and methyl tertiary butyl ether, mixed solvent of methanol and acetone, mixed solvent of ethanol and acetone, mixed solvent of ethanol and methyl tertiary butyl ether.
  • It may be any one mixed solvent selected from the group consisting of a solvent, a mixed solvent of dimethyl sulfoxide, ethanol, and ethyl acetate. More preferably, it may be a mixed solvent of ethanol and ethyl acetate.
  • crystallization under organic solvent conditions according to the present invention has excellent advantages in that it minimizes the production of related substances and produces the target salt without an additional purification process.
  • the internal temperature of the reactor is adjusted to 15 °C to 35 °C, preferably 20 °C to 30 °C to prepare a mixed solution of acid and organic solvent.
  • the acidic salt represented by Chemical Formula 1-1 can be crystallized.
  • the acid used to crystallize the acid salt represented by Formula 1-1 may be, for example, hydrochloric acid, glutamic acid, malonic acid, succinic acid, tartaric acid, oxalic acid, fumaric acid, phosphoric acid, and/or methanesulfonic acid.
  • the acid and the organic solvent may be provided as a mixed solution, and the organic solvent in the mixed solution may be selected from the organic solvents presented above.
  • the crystal when the acid used for crystallization in Formula 1-1 is fumaric acid, the crystal has the chemical structure of Formula 1-2 below.
  • the salt After preparing the salt, the salt can be dried at 40 to 60° C. for 10 to 14 hours to lower the moisture content contained in the compound represented by Formula 4. Through this, the water content of the compound represented by Formula 4 can be significantly lowered, thereby maximizing the yield of the target compound.
  • step 3 crystallization of the acid salt represented by Formula 1-1 may be performed two or more times.
  • the acid salt represented by Formula 1-1 is extracted using the organic solvent, and then a mixed solution of the acid or its organic solvent is supplied. Thus, recrystallization of the acid salt represented by Chemical Formula 1-1 is performed.
  • a base may be additionally used to dissociate the acid salt.
  • the base for dissociation of the acid salt is potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methylate, potassium butyrate, or cesium carbonate, or a mixture of two or more thereof.
  • a washing step using a solvent used after completion of the reaction in each step may be further included.
  • step 3 When step 3 is optionally performed, the reaction is performed together with step 2, so that the reaction can be performed in two steps rather than three steps.
  • the present invention provides a production method as shown in Scheme 2 below:
  • the present invention provides a method for preventing gastrointestinal ulcers, gastrointestinal inflammatory diseases, or gastric acid-related diseases, comprising the compound of Formula 1, or a pharmaceutically acceptable salt thereof (preferably Formula 1-1 or 1-2); A pharmaceutical composition for treatment is provided.
  • the present invention provides a compound of formula 1 as defined in any of the embodiments described herein, or a pharmaceutically acceptable salt thereof, for use as a medicament.
  • the present invention provides a compound of formula 1 as defined in any of the embodiments described herein, or a pharmaceutically acceptable salt thereof, for use in the prevention or treatment of gastrointestinal ulcers, gastrointestinal inflammatory diseases or gastric acid-related diseases. do.
  • the present invention provides a method for treating gastrointestinal ulcers, gastrointestinal inflammatory diseases, or gastric acid-related diseases, comprising administering a therapeutically effective amount of the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof to a subject in need thereof. provides.
  • the present invention relates to a compound of formula 1, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of diseases or conditions for which acid secretion inhibitors are prescribed, such as gastrointestinal ulcers, gastrointestinal inflammatory diseases or gastric acid-related diseases. Provides a purpose.
  • the present invention provides a compound of Formula 1, or a pharmaceutically acceptable salt thereof, as defined in any of the embodiments described herein, for use in the treatment of a disease or condition for which an acid secretion inhibitor is prescribed.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula 1, or a pharmaceutically acceptable salt thereof, as defined in any of the embodiments described herein, for the treatment of diseases or conditions for which acid secretion inhibitors are prescribed. do.
  • the present invention provides a gastric acid secretion inhibitor comprising the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof.
  • the gastrointestinal ulcer refers to an ulcer that occurs in the digestive tract, including both the stomach and intestines. Examples include, but are not limited to, peptic ulcer, gastric ulcer, duodenal ulcer, NSAID-induced ulcer, acute stress ulcer, Zollinger-Ellison syndrome, etc. If the ulcer becomes severe, it can lead to cancer. For example, in the case of the above stomach ulcer, as the disease becomes more severe, it may develop into stomach cancer.
  • gastrointestinal ulcers may include damage to the gastric mucosa or small intestine mucosa caused by drugs or alcohol.
  • it may be gastric mucosal damage or small intestine mucosal damage induced by NSAIDs or alcohol.
  • the gastrointestinal inflammatory disease refers to a disease caused by inflammation of the gastrointestinal tract.
  • gastritis e.g., acute hemorrhagic gastritis, chronic superficial gastritis, chronic atrophic gastritis
  • inflammatory bowel disease e.g., gastric MALT lymphoma.
  • gastric acid-related disease refers to a disease caused by excessive secretion of gastric acid.
  • examples include, but are not limited to, erosive esophagitis, non-erosive esophagitis, reflux esophagitis, symptomatic gastroesophageal reflux disease (symptomatic GERD), functional dyspepsia, hyperacidity, upper gastrointestinal bleeding due to invasive stress, etc.
  • symptomatic GERD symptomatic gastroesophageal reflux disease
  • the gastrointestinal ulcer, gastrointestinal inflammatory disease or gastric acid-related disease includes peptic ulcer, gastric ulcer, duodenal ulcer, NSAID-induced ulcer, acute stress ulcer, Zollinger-Ellison syndrome, and Helicobacter pylori.
  • Pylori Helicobacter pylori
  • gastritis gastritis
  • erosive esophagitis non-erosive esophagitis
  • reflux esophagitis inflammatory bowel disease
  • symptomatic gastroesophageal reflux disease symptomatic GERD
  • the pharmaceutical composition may contain the compound of the present invention together with a pharmaceutically acceptable carrier.
  • a pharmaceutically acceptable carrier includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic agents, absorption delay agents, etc. that are physiologically compatible.
  • compositions of the present invention may take various forms. This includes, for example, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, liposomes and suppositories.
  • liquid solutions e.g., injectable and infusible solutions
  • dispersions or suspensions tablets, pills, powders, liposomes and suppositories.
  • tablets, pills, powders, liposomes and suppositories e.g., suppositories.
  • the form depends on the intended mode of administration and therapeutic use.
  • compositions are in the form of compositions similar to injectables and infusible solutions.
  • One mode of administration is parenteral (eg, intravenous, subcutaneous, intraperitoneal, intramuscular).
  • Oral administration in solid dosage forms may be presented, for example, as hard or soft capsules, pills, sachets, lozenges or tablets, each containing a predetermined amount of one or more compounds of the invention.
  • oral administration may be in powder or granule form.
  • oral administration may be in the form of a liquid dosage.
  • Liquid dosage forms for oral administration include, for example, pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs, containing inert diluents (e.g., water) commonly used in the art.
  • parenteral dosage forms in another embodiment, includes parenteral dosage forms.
  • Parenteral administration includes, for example, subcutaneous injection, intravenous injection, intraperitoneal injection, intramuscular injection, intrasternal injection, and infusion.
  • injectable preparations i.e., sterile injectable aqueous or oleaginous suspensions
  • suitable dispersing, wetting and/or suspending agents may be formulated according to the known art, using suitable dispersing, wetting and/or suspending agents.
  • compositions of the invention may be prepared by any well-known pharmaceutical technique, such as effective formulation and administration procedures.
  • the compounds of the invention are administered in amounts effective to treat the conditions described herein.
  • the compounds of the invention may be administered as the compounds themselves or, alternatively, as pharmaceutically acceptable salts.
  • the compounds themselves or pharmaceutically acceptable salts thereof will simply be referred to as compounds of the invention.
  • the compounds of the invention are administered by any suitable route, in the form of pharmaceutical compositions suitable for said route, and in dosages effective for the intended treatment.
  • Compounds of the invention may be administered orally, rectally, vaginally, parenterally, or topically.
  • the compounds of the present invention can preferably be administered orally.
  • Oral administration may involve swallowing the compound to enter the gastrointestinal tract.
  • the compounds of the invention may also be administered directly to the bloodstream, muscles, or internal organs.
  • suitable means for parenteral administration include intravenous, intraarterial, intraperitoneal, intramuscular and subcutaneous.
  • the dosage regimen for the compounds of the present invention and/or compositions containing such compounds will depend on the type of patient, age, weight, gender and medical condition. severity of symptoms; route of administration; and the activity of the specific compound used. Accordingly, dosing regimens can vary widely.
  • the total daily dosage of a compound of the invention is typically from about 0.001 to about 100 mg/kg (i.e., mg of compound of the invention per kg of body weight) for the treatment of the presenting condition discussed herein. )am.
  • the manufacturing method according to the present invention has the advantage of allowing the reaction to be performed under mild conditions that enable mass production while greatly shortening the manufacturing process. In addition, despite the above shortening of the process, it has the advantage of improving process efficiency due to excellent yield, simplifying the manufacturing process with salt, minimizing the generation of related substances, and increasing yield. This can provide useful advantages for industrial mass production.
  • the filtrate was concentrated under reduced pressure at 35-45°C, and then 3,851 g of 2-propanol was added to the concentrate, then the temperature was raised to an internal temperature of 60-70°C and stirred for 10 minutes. Then, it was cooled to an internal temperature of 20-30°C and stirred for 12 hours. Then, it was cooled to an internal temperature of 0-5°C and stirred for 1 hour. When stirring was completed, the resulting crystals were filtered under reduced pressure, and the filtrate was washed with 1650 g of 2-propanol. The washed filtrate was dried at a temperature range of 45 to 55 °C for more than 12 hours to obtain 1145.8 g of the compound represented by Formula 4. (Yield: 91.9% / Purity 99.9%)
  • Step 2 5-(2-Fluorophenyl)-4-methoxy-1-((6-methoxypyridin-3-yl)sulfonyl) -1H -pyrrole-3-carbaldehyde (compound of Formula 4 ) 30.0 g and 119 g of methanol were added and stirred at room temperature for 10 minutes. 9.5 g (12 M in water) of methylamine was added and stirred for 1 hour at an internal temperature of 20-30°C. It was then cooled to an internal temperature of 0-10°C, 1.4 g of sodium borohydride was added, the temperature was raised to an internal temperature of 20-30°C, and the reaction was completed by stirring for 2 hours.
  • Step 3 The filtrate was concentrated under reduced pressure at 35-45 °C, 71 g of ethanol, 189 g of ethyl acetate, and 8.9 g of fumaric acid were added to the concentrate, and stirred for more than 12 hours at an internal temperature of 20-30 °C. When stirring was completed, the resulting crystals were filtered under reduced pressure, and the filtrate was washed with 54 g of ethyl acetate. The washed filtrate was dried at a temperature range of 45 to 55 °C for more than 12 hours to obtain 36.6 g of the compound represented by Chemical Formula 1-2. (Yield: 91.3% / Purity 99.7%)
  • step 1 the importance of selecting a suitable organic solvent in the manufacturing process of step 1 according to the present invention was confirmed.

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Abstract

La présente invention concerne un procédé de préparation de dérivés de 6-méthoxypyridin-3-yl. Le procédé de préparation selon la présente invention présente l'avantage de permettre à la réaction d'être réalisée dans des conditions modérées permettant une production de masse conjointement avec un raccourcissement significatif du procédé de préparation. En outre, la présente invention présente l'avantage d'améliorer l'efficacité de traitement par un excellent rendement malgré le procédé raccourci tel que ci-dessus, de simplifier le procédé de préparation à l'aide d'un sel, de réduire au minimum la génération de substances associées, et d'augmenter le rendement. Par conséquent, la présente invention peut apporter des avantages utiles pour la production industrielle à grande échelle.
PCT/KR2023/006926 2022-05-23 2023-05-22 Procédé de préparation de dérivés de 6-méthoxypyridin-3-yl WO2023229322A1 (fr)

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Application Number Priority Date Filing Date Title
KR20220062991 2022-05-23
KR10-2022-0062991 2022-05-23
KR1020230010923A KR20230163283A (ko) 2022-05-23 2023-01-27 6-메톡시피리딘-3-일 유도체의 제조방법
KR10-2023-0010923 2023-01-27

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Publication number Priority date Publication date Assignee Title
US20160009646A1 (en) * 2013-02-28 2016-01-14 Takeda Pharmaceutical Company Limited Method for producing sulfonyl chloride compound
KR20160127646A (ko) * 2015-04-27 2016-11-04 주식회사 대웅제약 신규의 4-메톡시 피롤 유도체 또는 이의 염 및 이를 포함하는 약학 조성물
KR20170113040A (ko) * 2016-03-25 2017-10-12 주식회사 대웅제약 1-(5-(2,4-다이플루오로페닐)-1-((3-플루오로페닐)술포닐)-4-메톡시-1h-피롤-3-일)-n-메틸메탄아민의 신규한 산부가염
KR20200033178A (ko) * 2018-09-19 2020-03-27 주식회사 대웅제약 4-메톡시 피롤 유도체의 제조 방법
KR20210156234A (ko) * 2020-06-17 2021-12-24 일동제약(주) 신규한 산 분비 억제제 및 이의 용도

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20160009646A1 (en) * 2013-02-28 2016-01-14 Takeda Pharmaceutical Company Limited Method for producing sulfonyl chloride compound
KR20160127646A (ko) * 2015-04-27 2016-11-04 주식회사 대웅제약 신규의 4-메톡시 피롤 유도체 또는 이의 염 및 이를 포함하는 약학 조성물
KR20170113040A (ko) * 2016-03-25 2017-10-12 주식회사 대웅제약 1-(5-(2,4-다이플루오로페닐)-1-((3-플루오로페닐)술포닐)-4-메톡시-1h-피롤-3-일)-n-메틸메탄아민의 신규한 산부가염
KR20200033178A (ko) * 2018-09-19 2020-03-27 주식회사 대웅제약 4-메톡시 피롤 유도체의 제조 방법
KR20210156234A (ko) * 2020-06-17 2021-12-24 일동제약(주) 신규한 산 분비 억제제 및 이의 용도

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