KR20020018560A - Novel process for preparing 3-aminomethyl-4-Z-methoxyiminopyrrolidine - Google Patents
Novel process for preparing 3-aminomethyl-4-Z-methoxyiminopyrrolidine Download PDFInfo
- Publication number
- KR20020018560A KR20020018560A KR1020010052027A KR20010052027A KR20020018560A KR 20020018560 A KR20020018560 A KR 20020018560A KR 1020010052027 A KR1020010052027 A KR 1020010052027A KR 20010052027 A KR20010052027 A KR 20010052027A KR 20020018560 A KR20020018560 A KR 20020018560A
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- compound
- catalyst
- solvent
- base
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
Abstract
Description
본 발명은 하기 화학식 (2)로부터 화학식 (3)을 거쳐 퀴놀론계 항생제 제미플록사신(Gemifloxacin)의 중간체인 하기 화학식 (1)의 화합물 또는 그의 산부가염을 합성하는 신규 방법에 관한 것으로, 기존의 방법에 비해 결정화 및 여과단계를 생략함으로써 수율을 획기적으로 증가시킬 수 있다.The present invention relates to a novel method for synthesizing a compound of formula (1) or an acid addition salt thereof, which is an intermediate of the quinolone antibiotic Gemifloxacin via formula (2) to formula (3). Compared with the step of eliminating the crystallization and filtration step can yield significantly increased.
[화학식 1][Formula 1]
[화학식 2][Formula 2]
[화학식 3][Formula 3]
화학식 (1)의 화합물은 새로운 퀴놀론 항생제로 개발하고 있는 원료 의약 물질(참조: 국내특허 출원번호 제 98-80504 호)의 핵심 중간체로서 제품의 제조 비용에 직접적인 영향을 미친다. 즉, 화학식 (1)의 화합물의 수율은 상업적 생산에 있어서 제조 단가에 미치는 영향이 크므로 수율을 향상시키기 위한 방안이 절실히 요망된다. 또한, 화학식 (1)의 화합물은 원료 의약 물질의 핵심 중간체이기 때문에 수율 향상으로 인한 품질의 저하가 없어야 한다.The compound of formula (1) is a key intermediate of the raw pharmaceutical material (see Korean Patent Application No. 98-80504), which is being developed as a new quinolone antibiotic, directly affecting the manufacturing cost of the product. That is, since the yield of the compound of the formula (1) has a large influence on the production cost in commercial production, a method for improving the yield is urgently desired. In addition, since the compound of formula (1) is a key intermediate of the raw pharmaceutical material, there should be no degradation in quality due to improved yield.
화학식 (1)의 화합물을 제조하는 방법으로 하기 반응식 1로 나타내어지는 방법이 알려져 있다. 구체적으로, 이 방법은 화학식 (2)의 화합물을 라니 니켈 촉매의 존재하에서 수소화시킨 후, 염기 조건에서 아민기를 보호하여 결정화 및 여과를 통해 화학식 (3)의 화합물을 수득한다. 이어서, 화학식 (3)의 화합물을 팔라듐 촉매의 존재하에서 수소화시켜 화학식 (4)의 화합물을 수득한 후, 메틸 옥심기를 도입시키고, 재결정화를 통해 최종 제품인 화학식 (1)의 화합물을 수득한다:As a method of preparing the compound of the formula (1), a method represented by the following Scheme 1 is known. Specifically, this process hydrogenates a compound of formula (2) in the presence of a Raney nickel catalyst, and then protects the amine group under basic conditions to obtain a compound of formula (3) through crystallization and filtration. The compound of formula (3) is then hydrogenated in the presence of a palladium catalyst to afford the compound of formula (4), followed by introducing methyl oxime groups, and recrystallization to give the final product, the compound of formula (1):
그러나 상기 방법에서는 생성된 화학식 (3)의 화합물에 대하여 결정화 및 여과 공정을 거치는데, 이때 많은 수율의 손실이 발생하여 결과적으로 화학식 (1) 화합물의 제조 단가가 상승하게 된다.However, the above method undergoes crystallization and filtration for the compound of formula (3), which results in a large loss of yield, resulting in an increase in the manufacturing cost of the compound of formula (1).
본 발명자들은 상기와 같은 문제점을 해결하기 위하여 기존의 제조 단계중 수율 손실이 가장 많은 결정화 및 여과 단계를 거쳐 화학식 (3)의 화합물을 수득하는 과정에서 결정화 및 여과 단계를 개선하기 위한 연구를 수행하였고, 그 결과 화학식 (2)의 화합물로부터 화학식 (3)의 화합물을 제조하는 공정에서 염기 물질의 당량을 증가시켜 반응을 수행하고, 화학식 (3)의 화합물을 화학식 (4)의 화합물로 수소화시킬 때 기존의 방법보다 상승된 온도 및 압력에서 수행하게 되면 결정화 및 여과 단계를 생략할 수 있고, 과량의 염기사용에 따른 수소화 촉매의 피독 현상을 감소시킬 수 있어서 화학식 (1)의 화합물을 품질 저하 없이 획기적인 수율로 수득할 수 있음을 밝혀내고 본 발명을 완성하게 되었다.The present inventors conducted a study to improve the crystallization and filtration step in the process of obtaining the compound of the formula (3) through the crystallization and filtration step that yields the most loss of yield in the existing manufacturing step to solve the above problems As a result, in the process for preparing the compound of formula (3) from the compound of formula (2), the reaction is carried out by increasing the equivalent of the base material, and when the compound of formula (3) is hydrogenated to the compound of formula (4) When performed at an elevated temperature and pressure than the conventional method, it is possible to omit the crystallization and filtration steps, and to reduce the poisoning phenomenon of the hydrogenation catalyst due to the use of an excessive amount of base. It was found that it can be obtained in yield to complete the present invention.
본 발명은 제 1 단계에서, 화학식 (2)의 화합물을 용매중에서 촉매의 존재하 및 염기의 존재하에 수소화 및 보호화시켜 화학식 (3)의 화합물을 수득하고, 제 2 단계에서, 수득한 화학식 (3)의 화합물을 용매중에서 촉매의 존재하에 수소화시켜 화학식 (4)의 화합물을 수득한 후, 제 3 단계에서, 수득한 화학식 (4)의 화합물을 메틸옥심화시켜 화학식 (1)의 화합물을 제조하는 방법에 관한 것으로, 이때 염기를 화학식 (2)의 화합물에 대해 3 내지 7 당량의 양으로 사용하고, 화학식 (3)의 화합물을 25 내지 60 ℃의 온도 및 1 내지 10 ㎏/㎠의 수소압력에서 수소화시킴을 특징으로 한다:In the first step, the compound of formula (2) is hydrogenated and protected in the solvent in the presence of a catalyst and in the presence of a base to give a compound of formula (3), and in the second step, the obtained formula ( The compound of 3) was hydrogenated in the presence of a catalyst in a solvent to give a compound of formula (4), and in the third step, the obtained compound of formula (4) was methyloxime to prepare a compound of formula (1). Wherein the base is used in an amount of 3 to 7 equivalents to the compound of formula (2), and the compound of formula (3) is subjected to a temperature of 25 to 60 ° C. and a hydrogen pressure of 1 to 10 kg / cm 2 Hydrogenation is characterized by:
[화학식 1][Formula 1]
[화학식 2][Formula 2]
[화학식 3][Formula 3]
본 발명에 따라 제조된 화학식 (1)의 화합물은 메탄설폰산염이나 염산염과 같은 산부가염으로 존재할 수 있다.The compounds of formula (1) prepared according to the invention may exist as acid addition salts, such as methanesulfonic acid salts or hydrochlorides.
본 발명에서 사용한 촉매와 시약의 양 및 종류 그리고 반응 온도 등을 포함한 반응 조건은 다음과 같다.Reaction conditions including the amount and type of catalysts and reagents used in the present invention and the reaction temperature are as follows.
제 1 단계에서 촉매로는 라니 니켈이 화학식 (2)의 화합물에 대해 5 내지 15 중량%의 양으로 사용된다.As a catalyst in the first step, Raney nickel is used in an amount of 5 to 15% by weight relative to the compound of the formula (2).
아민기를 보호하는데 있어서 수소이온 농도 조절에 사용되는 염기로는 수산화칼륨 및 수산화나트륨이 모두 가능하며, 이는 상기 화학식 (2)의 화합물에 대해 3 내지 7 당량의 양으로 사용된다.The bases used to adjust the hydrogen ion concentration in protecting the amine group may be both potassium hydroxide and sodium hydroxide, which are used in an amount of 3 to 7 equivalents based on the compound of formula (2).
이때, 라니-니켈 촉매하의 수소화 반응은 반응온도가 높을수록 반응속도가 빨라지지만 화합물의 분해로 인한 부반응을 방지하기 위하여 40℃ 이하로 유지하는 것이 바람직하다. 또한, 보호화 반응은 10℃ 이하, 바람직하게는 5℃ 이하의 온도에서 수행한다.At this time, the hydrogenation reaction under Raney-Nickel catalyst is faster the reaction rate is higher the reaction temperature, but it is preferable to maintain below 40 ℃ to prevent side reactions due to decomposition of the compound. In addition, the protection reaction is carried out at a temperature of 10 ° C or less, preferably 5 ° C or less.
제 2 단계에서 촉매로는 탄소에 담지된 팔라듐, 알루미나에 담지된 팔라듐 및 라니 니켈 등으로 구성된 그룹중에서 선택된 촉매가 화학식 (3)의 화합물에 대해 5 내지 25 중량%의 양으로 사용된다.In the second step, a catalyst selected from the group consisting of palladium supported on carbon, palladium supported on alumina, Raney nickel, and the like is used in an amount of 5 to 25% by weight based on the compound of the formula (3).
제 2 단계에서 수소 압력은 1 내지 10㎏/㎠이 사용된다. 이때 반응온도는25 내지 60℃ 이며, 반응온도가 높을수록 반응 시간이 짧아지나, 60℃ 이상에서는 반응물이 분해되기 시작하기 때문에 60℃ 이하의 온도를 사용하는 것이 바람직하다.In the second stage, the hydrogen pressure is 1 to 10 kg / cm 2. At this time, the reaction temperature is 25 to 60 ℃, the reaction time is shorter as the reaction temperature is higher, but it is preferable to use a temperature of 60 ℃ or less because the reactant starts to decompose at 60 ℃ or more.
본 발명에 따른 방법에서 반응은 모두 동일한 용매의 존재하에서 진행하였다. 사용될 수 있는 용매로는 이소프로필 알콜, 테트라하이드로푸란, 디메톡시에탄 등이 포함되며, 이들은 물을 1이라 할때, 1 내지 10의 부피비로 각각 물과 혼합하여 사용된다.In the process according to the invention the reactions all proceeded in the presence of the same solvent. Solvents that may be used include isopropyl alcohol, tetrahydrofuran, dimethoxyethane, and the like, which are used in admixture with water in a volume ratio of 1 to 10, when water is 1.
반응 순서에 있어서 기존의 방법은 화학식 (2)의 화합물을 반응시킨 후, 40 내지 60℃의 온도까지 가열하고, 층을 분리하여 유기층을 취하고, 추가의 용매를 첨가하여 냉각시키고 결정화한 후 여과 및 건조를 통해 화학식 (3)의 화합물을 분말 형태로 수득한다. 이에 반해, 본 발명에 따른 방법은 결정화 및 여과 단계 없이 화학식 (3)의 화합물까지 반응시킨 후 층을 분리하여 유기층만을 취하고 촉매를 첨가하여 바로 다음 단계인 수소화 공정을 수행한다. 따라서, 본 발명에 따른 방법은 결정화 및 여과 단계를 생략함으로써 목적하는 화학식 (1)의 화합물을 고수율로 수득할 수 있다.The conventional method in the reaction sequence is the reaction of the compound of formula (2), then heated to a temperature of 40 to 60 ℃, the layers are separated to take the organic layer, the addition of an additional solvent to cool and crystallize and then Drying yields the compound of formula (3) in powder form. In contrast, the process according to the present invention is reacted to the compound of formula (3) without crystallization and filtration steps, and the layers are separated to take only the organic layer and the catalyst is added to carry out the hydrogenation process, which is the next step. Thus, the process according to the invention can obtain the desired compound of formula (1) in high yield by omitting the crystallization and filtration steps.
본 발명에 따른 방법에 의해 제조된 화학식 (1)의 화합물은 퀴놀론 항생제를 제조하는데 중간체로서 사용될 수 있다.Compounds of formula (1) prepared by the process according to the invention can be used as intermediates in the preparation of quinolone antibiotics.
이하 실시예 및 비교예를 통해 본 발명을 예시하지만 이들로 본 발명을 한정하는 것으로 이해되어서는 안된다.The following Examples and Comparative Examples illustrate the invention but should not be construed as limiting the invention thereto.
실시예 1Example 1
단계 1Step 1
화학식 (2)의 화합물에서 화학식 (3)의 화합물로의 전환 (1)Conversion of a compound of formula (2) to a compound of formula (3) (1)
300 ㎖ 고압 반응기에 화학식 (2)의 화합물 10g, 라니-니켈 1g, 디메톡시에탄 57㎖ 및 물 10㎖를 넣고 40℃ 및 4㎏/㎠의 수소압력에서 교반하였다. 반응시작한지 6시간 후 규조토로 여과하고 생성물에 디-t-부틸 디카보네이트 1.2당량을 투입한 후 -10℃로 냉각시켰다. 여기에 온도가 5℃를 넘지않는 범위에서 수산화칼륨 6당량(화학식 (2)의 화합물에 대해)을 투입하면서 30분간 교반하고, 반응후 초산 6.6당량을 넣고 40℃까지 가열한 다음 층 분리에 의해 유기층을 취하였다. 생성물을 HPLC에 의해 분석한 결과 화학식 (2)의 화합물은 화학식 (3)의 화합물로 99% 전환되었다.10 g of the compound of formula (2), 1 g of Raney-nickel, 57 ml of dimethoxyethane and 10 ml of water were added to a 300 ml high-pressure reactor, and the mixture was stirred at 40 ° C. and hydrogen pressure of 4 kg / cm 2. Six hours after the start of the reaction, the mixture was filtered through diatomaceous earth, 1.2 equivalents of di-t-butyl dicarbonate was added to the product, and the mixture was cooled to -10 ° C. The mixture was stirred for 30 minutes while adding 6 equivalents of potassium hydroxide (relative to the compound of Formula (2)) in a temperature not exceeding 5 ° C. After the reaction, 6.6 equivalents of acetic acid was added and heated to 40 ° C, followed by layer separation The organic layer was taken. The product was analyzed by HPLC and the compound of formula (2) was 99% converted to the compound of formula (3).
단계 2Step 2
화학식 (3)의 화합물에서 화학식 (1)의 화합물의 메탄설폰산염으로의 전환Conversion of Compound of Formula (3) to Methanesulfonate of Formula (1)
상기 단계 1에서 수득한 유기층에 디메톡시에탄 90㎖, 물 40㎖ 및 5% Pd/C 1.35g을 첨가하여 50℃의 온도 및 1㎏/㎠의 수소압력에서 24시간동안 교반한 후 여과하여 화학식 (4)의 화합물을 얻었다. 여과한 용액에 메톡시아민-하이드로클로라이드 4.3g 및 소듐아세테이트 4.2g을 넣고 상온에서 4 시간동안 교반하였다. 디메톡시에탄 용매를 날리고 에틸아세테이트를 이용하여 층분리를 실시하였다. 층을 분리하여 유기층을 취한 후 에틸아세테이트를 진공하에서 날렸다. 그후, 메탄올과 메탄술폰산 3당량을 넣고 상온에서 24시간동안 교반하여 생성물을 수득하고, 이 생성물을 여과한 후 메탄올을 사용하여 재결정하여 3-아미노메틸-4-Z-메톡시이미노피롤리딘 디메틸설포네이트를 화학식 (2)의 화합물을 기준으로 하여 60%의 수율로 수득하였다.90 ml of dimethoxyethane, 40 ml of water and 1.35 g of 5% Pd / C were added to the organic layer obtained in Step 1, stirred at a temperature of 50 ° C. and hydrogen pressure of 1 kg / cm 2 for 24 hours, and then filtered. The compound of (4) was obtained. 4.3g of methoxyamine-hydrochloride and 4.2g of sodium acetate were added to the filtered solution, and the mixture was stirred at room temperature for 4 hours. The dimethoxyethane solvent was blown off and the layers separated using ethyl acetate. The layers were separated, the organic layer was taken, and ethyl acetate was blown under vacuum. Thereafter, 3 equivalents of methanol and methanesulfonic acid were added and stirred at room temperature for 24 hours to obtain a product. The product was filtered and then recrystallized from methanol to give 3-aminomethyl-4-Z-methoxyiminopyrrolidine dimethyl. Sulfonates were obtained in a yield of 60% based on the compound of formula (2).
실시예 2Example 2
화학식 (2)의 화합물에서 화학식 (3)의 화합물로의 전환 (2)Conversion of a compound of formula (2) to a compound of formula (3) (2)
디-t-부틸 디카보네이트 및 수산화칼륨의 투입량을 각각 1.1 당량 및 4 당량으로 사용하는 것을 제외하고 실시예 1의 단계 1과 동일한 방법으로 실험을 수행하였다. 생성물을 HPLC에 의해 분석한 결과 화학식 (2)의 화합물은 화학식 (3)의 화합물로 95% 전환되었다.The experiment was carried out in the same manner as in Step 1 of Example 1, except that 1.1 and 4 equivalents of di-t-butyl dicarbonate and potassium hydroxide were used. The product was analyzed by HPLC and the compound of formula (2) was 95% converted to the compound of formula (3).
실시예 3Example 3
화학식 (3)의 화합물에서 화학식 (1)의 화합물의 메탄설폰산염으로의 전환(2)Conversion of Compounds of Formula (3) to Methanesulfonates (2)
실시예 2에서 수득한 화학식 (3)의 화합물을 사용하여 실시예 1의 단계 2와 동일한 방법으로 실험을 수행하여 3-아미노메틸-4-Z-메톡시이미노피롤리딘 디메틸설포네이트를 화학식 (2)의 화합물을 기준으로 하여 56%의 수율로 수득하였다.Experiment was carried out in the same manner as in Step 2 of Example 1, using the compound of formula (3) obtained in Example 2 to obtain 3-aminomethyl-4-Z-methoxyiminopyrrolidine dimethylsulfonate Obtained in a yield of 56% based on the compound of 2).
비교예 1Comparative Example 1
실시예 2에서 수득한 생성물에 이소프로필 알콜 40㎖ 및 물 40㎖를 한번에투입한 후, 교반하면서 물 40㎖를 2 내지 3시간에 걸쳐 투입하였다. 투입이 종료된 후 상온에서 12 내지 16시간동안 교반한 후 5℃로 냉각하여 여과한 다음 건조시켰다. 이 건조된 화합물로 실시예 1의 단계 2와 동일한 방법으로 실험을 수행하되 디메톡시에탄은 건조된 화합물 질량의 15부피배를 사용하고, 보레이트 버퍼용액을 건조된 화합물 질량만큼 투입하여 반응온도는 상온, 수소압력은 0.1kg/㎠ 로 하여 수소화 반응을 실시하였다. 수득한 3-아미노메틸-4-Z-메톡시이미노피롤리딘 디메틸설포네이트의 수율은 화학식 (2)의 화합물을 기준으로 하여 43% 이었다.40 ml of isopropyl alcohol and 40 ml of water were added to the product obtained in Example 2, and 40 ml of water was added over 2 to 3 hours while stirring. After the addition was completed, the mixture was stirred at room temperature for 12 to 16 hours, cooled to 5 ° C., filtered, and dried. Experiment with the dried compound in the same manner as in step 2 of Example 1, dimethoxyethane is used 15 times the volume of the dried compound mass, borate buffer solution is added as much as the mass of the dried compound and the reaction temperature is room temperature And hydrogen pressure was 0.1 kg / cm <2>, and the hydrogenation reaction was performed. The yield of 3-aminomethyl-4-Z-methoxyiminopyrrolidine dimethylsulfonate obtained was 43% based on the compound of formula (2).
본 발명에 따른 방법에 의하면, 전구체 물질인 화학식 (3)의 화합물의 결정화 및 여과 단계를 생략함으로써 기존의 방법보다 획기적으로 높은 수율로 화학식 (1)의 화합물을 수득할 수 있었다.According to the method according to the present invention, the compound of formula (1) can be obtained in a significantly higher yield than the conventional method by omitting the crystallization and filtration steps of the compound of formula (3) which is a precursor material.
Claims (7)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20000051540 | 2000-09-01 | ||
| KR1020000051540 | 2000-09-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20020018560A true KR20020018560A (en) | 2002-03-08 |
Family
ID=19686748
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020010052027A KR20020018560A (en) | 2000-09-01 | 2001-08-28 | Novel process for preparing 3-aminomethyl-4-Z-methoxyiminopyrrolidine |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2004507524A (en) |
| KR (1) | KR20020018560A (en) |
| AU (1) | AU2001280244A1 (en) |
| WO (1) | WO2002018336A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9920917D0 (en) | 1999-09-03 | 1999-11-10 | Sb Pharmco Inc | Novel process |
| GB9920919D0 (en) | 1999-09-03 | 1999-11-10 | Sb Pharmco Inc | Novel compound |
| KR100517638B1 (en) | 2002-04-08 | 2005-09-28 | 주식회사 엘지생명과학 | New process for preparing acid salts of Gemifloxacin |
| KR100653334B1 (en) | 2003-03-07 | 2006-12-04 | 주식회사 엘지생명과학 | New process for preparing 4-aminomethyl-3-alkoxyiminopyrrolidine methanesulphonate |
| CN113773240B (en) * | 2021-10-12 | 2022-05-31 | 北京阳光诺和药物研究股份有限公司 | Preparation method of gemifloxacin side chain compound |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5328163A (en) * | 1976-08-27 | 1978-03-16 | Yamanouchi Pharmaceut Co Ltd | Novel 1-benzyl-3-pyrrolidoneoxime derivatives and their preparation |
| EP0688772A1 (en) * | 1994-06-16 | 1995-12-27 | LG Chemical Limited | Novel quinoline carboxylic acid derivatives having 7-(4-amino-methyl-3-oxime) pyrrolidine substituents and processes for their preparation |
| KR960022461A (en) * | 1994-12-30 | 1996-07-18 | 성재갑 | 4-aminomethylpyrrolidin-3-one-0-alkyl or aryl oxime derivatives and preparation method thereof |
| WO1999044991A1 (en) * | 1998-03-04 | 1999-09-10 | Lg Chemical Ltd. | Process for preparing a protected 4-aminomethyl-pyrrolidin-3-one |
| KR20020003786A (en) * | 2000-07-05 | 2002-01-15 | 김충섭 | Method of preparing 3-methoxyimino-4-aminomethylpyrrolidine derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01100165A (en) * | 1987-10-13 | 1989-04-18 | Shionogi & Co Ltd | Oxime or hydroxylamine derivative based antimicrobial agent |
| US5276041A (en) * | 1991-11-08 | 1994-01-04 | Kaken Pharmaceutical Co., Ltd. | Oxime derivatives |
-
2001
- 2001-08-28 KR KR1020010052027A patent/KR20020018560A/en active Search and Examination
- 2001-08-29 WO PCT/KR2001/001466 patent/WO2002018336A1/en active Application Filing
- 2001-08-29 JP JP2002523454A patent/JP2004507524A/en active Pending
- 2001-08-29 AU AU2001280244A patent/AU2001280244A1/en not_active Abandoned
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5328163A (en) * | 1976-08-27 | 1978-03-16 | Yamanouchi Pharmaceut Co Ltd | Novel 1-benzyl-3-pyrrolidoneoxime derivatives and their preparation |
| EP0688772A1 (en) * | 1994-06-16 | 1995-12-27 | LG Chemical Limited | Novel quinoline carboxylic acid derivatives having 7-(4-amino-methyl-3-oxime) pyrrolidine substituents and processes for their preparation |
| KR960022461A (en) * | 1994-12-30 | 1996-07-18 | 성재갑 | 4-aminomethylpyrrolidin-3-one-0-alkyl or aryl oxime derivatives and preparation method thereof |
| WO1999044991A1 (en) * | 1998-03-04 | 1999-09-10 | Lg Chemical Ltd. | Process for preparing a protected 4-aminomethyl-pyrrolidin-3-one |
| KR20020003786A (en) * | 2000-07-05 | 2002-01-15 | 김충섭 | Method of preparing 3-methoxyimino-4-aminomethylpyrrolidine derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001280244A1 (en) | 2002-03-13 |
| WO2002018336A1 (en) | 2002-03-07 |
| JP2004507524A (en) | 2004-03-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2011281421A1 (en) | Process for preparing aminobenzoylbenzofuran derivatives | |
| KR20020018560A (en) | Novel process for preparing 3-aminomethyl-4-Z-methoxyiminopyrrolidine | |
| CN114195712B (en) | Intermediate capable of being used for preparing procaterol hydrochloride and preparation method thereof | |
| CN107935866B (en) | Preparation method of dapoxetine hydrochloride impurity | |
| CN114105872B (en) | Intermediate for preparing procaterol hydrochloride and preparation method thereof | |
| CA2686312C (en) | Process for preparing aromatase inhibitors | |
| WO2022083728A1 (en) | Intermediate of pregabalin and preparation method therefor | |
| WO2021228034A1 (en) | Preparation method of (5-fluoro-2, 3-dihydrobenzofuran-4-yl) methanamine or its salt, and intermediates thereof | |
| CN114989178A (en) | Spiro [ beta-lactam-3, 3' -oxindole ] derivative and preparation method and application thereof | |
| CN109824520B (en) | Preparation method of cis-4-methylcyclohexylamine | |
| US5099067A (en) | Use of ammonium formate as a hydrogen transfer reagent for reduction of chiral nitro compounds with retention of configuration | |
| CN114213323B (en) | New process for synthesizing procaterol hydrochloride | |
| EP3904340B1 (en) | Synthesis method for halofuginone and intermediate thereof | |
| CN115784922B (en) | Preparation method of (2S) -2-amino-4- (cyclopropyl/cyclobutyl) butyric acid | |
| CN115368250B (en) | Method for resolution of formoterol chiral intermediate | |
| CN110963967B (en) | Preparation method of 2-methyl-4-aminoquinoline | |
| EP0982297A2 (en) | Process for the preparation of hydroxy-pyrrolidinyl hydroxamic acid derivatives being opioid kappa receptor agonists | |
| CN113214255B (en) | Synthesis method of 2, 6-diazaspiro [3.5] nonane-6-tert-butyl formate and salt thereof | |
| US20040235928A1 (en) | Process for the preparation of optically active amines or salts thereof | |
| KR20090061018A (en) | Process for the preparation of amines | |
| US6384244B2 (en) | Process for preparing cis- aminochromanols | |
| CN118546149A (en) | Preparation method of 5-spiro camptothecin | |
| CN118724841A (en) | Preparation method of N-aminopiperidine dihydrochloride | |
| CN117603094A (en) | Synthesis method of amino-protected 2-aminomethyl olefine acid derivative | |
| CN116063186A (en) | Process and intermediates for the preparation of (S) -2-amino-5, 7-difluoro-1, 2,3, 4-tetrahydronaphthalene hydrogen halides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| N231 | Notification of change of applicant | ||
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| AMND | Amendment | ||
| E601 | Decision to refuse application | ||
| AMND | Amendment | ||
| J201 | Request for trial against refusal decision | ||
| E801 | Decision on dismissal of amendment | ||
| B601 | Maintenance of original decision after re-examination before a trial | ||
| J301 | Trial decision |
Free format text: TRIAL DECISION FOR APPEAL AGAINST DECISION TO DECLINE REFUSAL REQUESTED 20050926 Effective date: 20070228 Free format text: TRIAL NUMBER: 2005101006476; TRIAL DECISION FOR APPEAL AGAINST DECISION TO DECLINE REFUSAL REQUESTED 20050926 Effective date: 20070228 |