KR19990000959A - Method for preparing 2-aminothiazolecarboxamide derivative - Google Patents
Method for preparing 2-aminothiazolecarboxamide derivative Download PDFInfo
- Publication number
- KR19990000959A KR19990000959A KR1019970024120A KR19970024120A KR19990000959A KR 19990000959 A KR19990000959 A KR 19990000959A KR 1019970024120 A KR1019970024120 A KR 1019970024120A KR 19970024120 A KR19970024120 A KR 19970024120A KR 19990000959 A KR19990000959 A KR 19990000959A
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- mmol
- compound
- solvent
- added dropwise
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
본 발명은 하기 화학식 2의 화합물을 용매중에서 티오닐클로라이드(SOCl2) 존재하에 반응시켜 하기 화학식 3의 화합물을 제조한 다음, 제조된 화학식 3의 화합물을 용매중에서 피리딘 존재하에 하기 화학식 4의 화합물과 반응시킴을 특징으로하여 하기 화학식 1의 2-아미노티아졸카르복사미드 유도체를 제조하는 방법에 관한 것이다.The present invention is prepared by reacting a compound of formula 2 in the presence of thionyl chloride (SOCl 2) in a solvent to prepare a compound of formula 3, and then reacting the compound of formula 3 with a compound of formula 4 in the presence of pyridine in a solvent It relates to a method for producing a 2-aminothiazole carboxamide derivative of the formula (1) characterized by the following.
[화학식 2][Formula 2]
[화학식 3][Formula 3]
[화학식 4][Formula 4]
[화학식 1][Formula 1]
상기식에서In the above formula
R1 은 C1-C2 알킬 또는 C3 알케닐을 나타내고,R1 represents C1-C2 alkyl or C3 alkenyl,
R2 는 C1-C2 알킬 또는 메톡시메틸을 나타낸다.R2 represents C1-C2 alkyl or methoxymethyl.
Description
본 발명은 하기 화학식 1로 표시되는 2-아미노티아졸카르복사미드 유도체의 제조방법에 관한 것이다.The present invention relates to a method for preparing the 2-aminothiazolecarboxamide derivative represented by the following formula (1).
화학식 1Formula 1
상기식에서In the above formula
R1 은 C1-C2 알킬 또는 C3 알케닐을 나타내고,R1 represents C1-C2 alkyl or C3 alkenyl,
R2 는 C1-C2 알킬 또는 메톡시메틸을 나타낸다.R2 represents C1-C2 alkyl or methoxymethyl.
상기 화학식 1의 화합물은 역병균(Pythiaceae) 및 노균(Peronosporaceae)과 같은 유주자 균류(Oomycetes)를 포함하는 대표적인 식물병원균이 야기시키는 식물병해에 유용하게 사용될 수 있다.The compound of Chemical Formula 1 may be usefully used in plant diseases caused by representative phytopathogens including Oomycetes such as Pythiaceae and Peronosporaceae.
대한민국 특허공개공보 제 95-5827 호에는 상기 화학식 1의 화합물을 포함한 여러가지 2-아미노 카르복사미드 유도체들의 제조방법이 기술되어 있는데, 이 방법에서는 할로겐화제로서 PCl5를 바람직하게 사용하고 있다. 그러나, PCl5를 사용하는 경우에는 반응중에 POCl3 가 생성되어 다음 반응에 문제를 일으키므로 다음 반응을 진행시키기 전에 사용된 용매와 함께 제거해주어야 하는데 이 POCl3 가 용이하게 제거되지 않는 문제점이 있을 뿐아니라 비경제적이고 생산현장에 적용시 다루기 어려운 문제점이 있다. 또한, 상기 반응에서는 두 번째 단계에서 염기로 트리에틸아민을 바람직하게 사용하고 있는데, 이 경우 수율이 저조하여 상기 PCl5를 사용함에 따른 문제점과 함께 공업적으로 적용하는데 좋지않은 영향을 미치고 있다.Korean Patent Publication No. 95-5827 discloses a method for preparing various 2-amino carboxamide derivatives including the compound of Formula 1, in which PCl5 is preferably used as the halogenating agent. However, in the case of using PCl5, POCl3 is generated during the reaction, which causes problems in the next reaction, so it must be removed together with the solvent used before proceeding with the next reaction, and this POCl3 is not easily removed. There is a problem that is difficult to deal with when applied to production sites. In addition, in the reaction, triethylamine is preferably used as a base in the second step. In this case, the yield is low, and it has an adverse effect on industrial application with the problem of using the PCl5.
이에 본 발명자들은 전술한 공지 방법의 문제점을 해결함에 있어 할로겐화제 및 염기의 선택이 매우 중요하게 작용함을 인식하고 보다 적합한 반응조건을 확립하기 위해 집중적인 연구를 수행하였으며, 그 결과 다음에 구체적으로 기술하는 방법에 따라 화학식 1의 화합물을 제조하게 되면 고순도의 목적화합물을 고수율로 그리고 경제적으로 제조할 수 있음을 발견하고 본 발명을 완성하게 되었다.Accordingly, the present inventors have conducted intensive studies to establish more suitable reaction conditions and recognize that the selection of the halogenating agent and the base plays a very important role in solving the problems of the known method described above. The preparation of the compound of formula (1) according to the described method has been found to be able to produce a high purity of the target compound in high yield and economically completed the present invention.
본 발명은 하기 화학식 2의 화합물을 용매중에서 티오닐클로라이드(SOCl2) 존재하에 반응시켜 하기 화학식 3의 화합물을 제조한 다음, 제조된 화학식 3의 화합물을 용매중에서 피리딘 존재하에 하기 화학식 4의 화합물과 반응시킴을 특징으로하여 하기 화학식 1의 2-아미노티아졸카르복사미드 유도체를 제조하는 방법에 관한 것이다.The present invention is prepared by reacting a compound of formula 2 in the presence of thionyl chloride (SOCl 2) in a solvent to prepare a compound of formula 3, and then reacting the compound of formula 3 with a compound of formula 4 in the presence of pyridine in a solvent It relates to a method for producing a 2-aminothiazole carboxamide derivative of the formula (1) characterized by the following.
화학식 2Formula 2
화학식 3Formula 3
화학식 4Formula 4
화학식 1Formula 1
본 발명에 따른 제조방법은 하기 반응식 1과 같이 간단히 나타낼 수 있다.The preparation method according to the present invention can be represented simply as in Scheme 1 below.
[반응식 1]Scheme 1
상기식에서 In the above formula
R1 은 C1-C2 알킬 또는 C3 알케닐을 나타내고,R1 represents C1-C2 alkyl or C3 alkenyl,
R2 는 C1-C2 알킬 또는 메톡시메틸을 나타낸다.R2 represents C1-C2 alkyl or methoxymethyl.
상기 제조방법을 다음에 자세히 설명한다.The manufacturing method will be described in detail below.
먼저, 화학식 3의 화합물을 제조함에 있어서, 용매로는 디클로로메탄, 1,2-디클로로에탄, 클로로포름, 사염화탄소 등과 같은 클로로알칸류 용매, 바람직하게는 디클로로메탄을 사용할 수 있으며, 반응액에 티오닐 클로라이드를 화학식 2의 화합물을 기준으로 하여 1.0∼1.2 당량 가하고 2∼4시간 동안 환류시킨다. 반응이 느리게 진행되거나 불순물이 많이 생기는 경우에는 N,N-디메틸포름아미드, N-메틸포름아미드 및 N-페닐-N-메틸포름아미드 중에서 선택된 1 종을 촉매로 사용함으로써 이러한 현상을 개선할 수 있다.First, in preparing the compound of Chemical Formula 3, a chloroalkane solvent such as dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, and preferably dichloromethane may be used, and thionyl chloride may be used in the reaction solution. Is added in an amount of 1.0 to 1.2 equivalents based on the compound of Formula 2 and refluxed for 2 to 4 hours. In the case of slow reaction or high impurities, this phenomenon can be improved by using one selected from N, N-dimethylformamide, N-methylformamide and N-phenyl-N-methylformamide as a catalyst. .
화학식 3의 화합물이 제조된 후 잔류한 염화수소나 할로겐화제와 같은 산류는 용매와 함께 제거하며, 제거되지 않는 경우에는 화학식 3의 화합물을 고체상태로 수득한 후 질소, 아르곤 등의 불활성기체로 건조시켜 사용한다. 수득된 화학식 3의 화합물이 용해되어 있는 클로로알칸류 용매를 0∼10℃로 냉각시킨 후 여기에 화학식 4의 화합물을 화학식 3의 화합물을 기준으로하여 1.0∼1.2 당량 가하고 천천히 피리딘을 적가하여 화학식 1의 화합물을 제조한다. 이 반응에서 염기로 사용되는 피리딘은 화학식 4의 화합물을 기준으로하여 통상 2.8∼3.0당량을 사용하는데, 본 발명에서는 염기로 피리딘을 선택하여 사용함으로써 트리에틸아민을 염기로 사용하는 선행발명에 비해 20% 이상의 수율 상승효과를 달성하고 있다. 적가가 끝난 후 1∼3시간동안 5 내지 20℃에서 반응을 진행시켜 반응이 완료되면 용매를 적당히 증류하여 제거한 후 알콜류와 물을 사용하여 결정화함으로써 목적화합물을 수득한다. 이때, 재결정을 이용하여 고순도의 화합물을 수득할 수도 있다.Acids such as hydrogen chloride or halogenating agent remaining after the compound of formula 3 are prepared are removed with a solvent. If not removed, the compound of formula 3 is obtained in a solid state and dried with an inert gas such as nitrogen or argon. use. After cooling the obtained chloroalkane solvent in which the compound of Formula 3 is dissolved at 0 to 10 ° C., 1.0 to 1.2 equivalents of the compound of Formula 4 are added to the compound of Formula 3, and pyridine is slowly added dropwise thereto. To prepare a compound. The pyridine used as the base in this reaction is generally used 2.8 ~ 3.0 equivalents based on the compound of formula (4), in the present invention by selecting a pyridine as the base 20 compared to the prior invention using triethylamine as a base Yield improvement of more than% is achieved. After completion of the dropwise addition, the reaction is carried out at 5 to 20 ° C. for 1 to 3 hours. When the reaction is completed, the solvent is appropriately distilled off and crystallized using alcohols and water to obtain a target compound. At this time, the compound of high purity may be obtained using recrystallization.
이상 설명한 제조방법에 따라 합성한 화학식 1 화합물의 대표적인 예를 하기 표 1에 나타내었다.Representative examples of the compound of Formula 1 synthesized according to the preparation method described above are shown in Table 1 below.
[표 1]TABLE 1
이하, 본 발명을 하기 실시예에 의거하여 보다 구체적으로 설명한다. 그러나, 이들 실시예는 본 발명에 대한 이해를 돕기위한 것일 뿐, 어떤 의미로든 본 발명의 범위가 이들 실시예로 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail based on the following examples. However, these examples are only for the understanding of the present invention, and the scope of the present invention in any sense is not limited to these examples.
합성synthesis
2-에틸아미노-4-에틸-티아졸-5-카르복시산 2.0g(10mmol)과 디클로로메탄 20g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g(12mmol)을 적가한 후 3시간동안 환류시켰다. 그 후 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃ 사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 20℃로 승온시키면서 2시간 동안 교반한 다음 용매를 증류하여 제거하였다. 잔류물을 물과 메탄올로 결정화 시킨 후 톨루엔과 에탄올로 재결정하여 표제화합물을 2.92g(9.1mmol; 수율 91%)수득하였다.2.0 g (10 mmol) of 2-ethylamino-4-ethyl-thiazole-5-carboxylic acid and 20 g of dichloromethane were added dropwise while stirring 1.43 g (12 mmol) of thionyl chloride at room temperature with reflux for 3 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C, followed by dropwise addition of pyridine 2.38 g (30 mmol). It was. After completion of the dropwise addition, the mixture was stirred for 2 hours while raising the temperature to 20 ° C, and then the solvent was distilled off. The residue was crystallized with water and methanol and recrystallized with toluene and ethanol to give 2.92 g (9.1 mmol; 91% yield) of the title compound.
합성synthesis
2-에틸아미노-4-에틸-티아졸-5-카르복시산 2.0g(10mmol), 디클로로메탄 20g 및 N-메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g (12mmol)을 적가한 후 2시간 동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 2.95g(9.2mmol; 수율 92%)을 수득하였다.2.0 g (10 mmol) of 2-ethylamino-4-ethyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N-methylformamide were added dropwise with 1.43 g (12 mmol) of thionyl chloride at room temperature while stirring. It was refluxed for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 2.95 g (9.2 mmol; yield 92%) of the title compound.
합성synthesis
2-에틸아미노-4-에틸-티아졸-5-카르복시산 2.0g(10mmol), 디클로로메탄 20g 및 N,N-디메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g (12mmol)을 적가한 후 2시간동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃ 사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 2.95g(9.2mmol; 수율 92%)을 수득하였다.2.0 g (10 mmol) of 2-ethylamino-4-ethyl-thiazole-5-carboxylic acid, 20 g of dichloromethane, and 0.1 g of N, N-dimethylformamide were added dropwise to 1.43 g (12 mmol) of thionyl chloride at room temperature with stirring. After refluxing for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 2.95 g (9.2 mmol; yield 92%) of the title compound.
합성synthesis
2-에틸아미노-4-에틸-티아졸-5-카르복시산 2.0g(10mmol), 디클로로메탄 20g 및 N-페닐-N-메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g(12mmol)을 적가한 후 2시간 동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃ 사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 3.01g (9.4mmol; 수율 94%)을 수득하였다.2.0 g (10 mmol) of 2-ethylamino-4-ethyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N-phenyl-N-methylformamide, while stirring 1.43 g (12 mmol) of thionyl chloride at room temperature Was added dropwise to reflux for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 3.01 g (9.4 mmol; 94% yield) of the title compound.
합성synthesis
2-에틸아미노-4-메틸-티아졸-5-카르복시산 1.86g(10mmol) 및 디클로로메탄 20g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g(12mmol)을 적가한 후 3시간동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃ 사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 2.68g(8.8mmol; 수율 88%)을 수득하였다.1.86 g (10 mmol) of 2-ethylamino-4-methyl-thiazole-5-carboxylic acid and 20 g of dichloromethane were added dropwise while stirring 1.43 g (12 mmol) of thionyl chloride at room temperature under reflux for 3 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 2.68 g (8.8 mmol; yield 88%) of the title compound.
합성synthesis
2-에틸아미노-4-메틸-티아졸-5-카르복시산 1.86g(10mmol), 디클로로메탄 20g 및 N-메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g (12mmol)을 적가한 후 2시간 동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃ 사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 2.64g(8.7mmol; 수율 87%)을 수득하였다.1.43 g (12 mmol) of thionyl chloride was added dropwise at room temperature while stirring 1.86 g (10 mmol) of 2-ethylamino-4-methyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N-methylformamide. It was refluxed for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 2.64 g (8.7 mmol; 87% yield) of the title compound.
합성synthesis
2-에틸아미노-4-메틸-티아졸-5-카르복시산 1.86g(10mmol), 디클로로메탄 20g 및 N,N-디메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g(12mmol)을 적가한 후 2시간 동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후, 실시예 1에서와 동일하게 실시하여 표제화합물 2.71g(8.9mmol; 수율 89%)을 수득하였다.1.43 g (12 mmol) of 2-ethylamino-4-methyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N, N-dimethylformamide were added dropwise at room temperature with stirring. After refluxing for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 2.71 g (8.9 mmol; 89% yield) of the title compound.
합성synthesis
2-에틸아미노-4-메틸-티아졸-5-카르복시산 1.86g(10mmol), 디클로로메탄 20g 및 N-페닐-N-메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g(12mmol)을 적가한 후 2시간동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후, 실시예 1에서와 동일하게 실시하여 표제화합물 2.77g(9.1mmol; 수율 91%)을 수득하였다.1.43 g (12 mmol) of thionyl chloride at room temperature while stirring 1.86 g (10 mmol) of 2-ethylamino-4-methyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N-phenyl-N-methylformamide Was added dropwise to reflux for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 2.77 g (9.1 mmol; 91% yield) of the title compound.
합성synthesis
2-에틸아미노-4-메톡시메틸-티아졸-5-카르복시산 2.16g(10mmol), 디클로로메탄 20g 및 N,N-디메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g(12mmol)을 적가한 후 2시간 동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후, 실시예 1에서와 동일하게 실시하여 표제화합물 2.11g(6.3mmol; 수율 63%)을 수득하였다.2.43 g (12 mmol) of thionyl chloride at room temperature while stirring 2.16 g (10 mmol) of 2-ethylamino-4-methoxymethyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N, N-dimethylformamide Was added dropwise to reflux for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 2.11 g (6.3 mmol; 63% yield) of the title compound.
합성synthesis
2-에틸아미노-4-메톡시메틸-티아졸-5-카르복시산 2.16g(10mmol), 디클로로메탄 20g 및 N-페닐-N-메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g(12mmol)을 적가한 후 2시간 동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후, 실시예 1에서와 동일하게 실시하여 표제화합물 2.28g(6.8mmol; 수율 68%)을 수득하였다.1.43 g of thionyl chloride at room temperature while stirring 2.16 g (10 mmol) of 2-ethylamino-4-methoxymethyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N-phenyl-N-methylformamide 12 mmol) was added dropwise and refluxed for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 2.28 g (6.8 mmol; 68% yield) of the title compound.
합성synthesis
2-메틸아미노-4-메틸-티아졸-5-카르복시산 1.72g(10mmol), 디클로로메탄 20g 및 N,N-디메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g (12mmol)을 적가한 후 2시간동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 1.76g(6mmol; 수율 60%)을 수득하였다.1.43 g (12 mmol) of thionyl chloride was added dropwise at room temperature while stirring 1.72 g (10 mmol) of 2-methylamino-4-methyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N, N-dimethylformamide. After refluxing for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 1.76 g (6 mmol; 60% yield) of the title compound.
합성synthesis
2-메틸아미노-4-에틸-티아졸-5-카르복시산 1.86g(10mmol), 디클로로메탄 20g 및 N,N-디메틸포름아미드 0.1g을 교반하면서 실온에서 티오닐 클로라이드 1.43g (12mmol)을 적가한 후 2시간 동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃ 사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 1.80g(5.9mmol; 수율 59%)을 수득하였다.1.86 g (10 mmol) of 2-methylamino-4-ethyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N, N-dimethylformamide were added dropwise to 1.43 g (12 mmol) of thionyl chloride at room temperature with stirring. It was then refluxed for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the dropwise addition was completed in the same manner as in Example 1 to obtain 1.80 g (5.9 mmol; 59% yield) of the title compound.
합성synthesis
2-메틸아미노-4-메톡시메틸-티아졸-5-카르복시산 2.02g(10mmol), 디클로로메탄 20g 및 N,N-디메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g(12mmol)을 적가한 후 2시간동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 1.31g(4.1mmol; 수율 41%)을 수득하였다.2.043 g (10 mmol) of 2-methylamino-4-methoxymethyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N, N-dimethylformamide, while stirring 1.43 g (12 mmol) of thionyl chloride at room temperature Was added dropwise to reflux for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 1.31 g (4.1 mmol; yield 41%) of the title compound.
합성synthesis
2-메틸아미노-4-메톡시메틸-티아졸-5-카르복시산 2.02g(10mmol), 디클로로메탄 20g 및 N-페닐-N-메틸포름아미드 0.1g을 교반하면서 실온에서 티오닐 클로라이드 1.43g(12mmol)을 적가한 후 2시간 동안 환류시켰다. 그 후, 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 1.57g(4.9mmol; 수율 49%)을 수득하였다.2.043 g (10 mmol) of 2-methylamino-4-methoxymethyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N-phenyl-N-methylformamide were stirred at room temperature with 1.43 g (12 mmol) of thionyl chloride at room temperature. ) Was added dropwise and refluxed for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C., followed by pyridine 2.38 g (30 mmol). Added dropwise. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 1.57 g (4.9 mmol; yield 49%) of the title compound.
합성synthesis
2-알릴아미노-4-메틸-티아졸-5-카르복시산 1.98g(10mmol), 디클로로메탄 20g 및 N,N-디메틸포름아미드 0.1g을 교반하면서, 실온에서 티오닐 클로라이드 1.43g (12mmol)을 적가한 후 2시간동안 환류시켰다. 그 후 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 1.56g(4.9mmol; 수율 49%)을 수득하였다.1.43 g (12 mmol) of thionyl chloride was added dropwise at room temperature while stirring 1.98 g (10 mmol) of 2-allylamino-4-methyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N, N-dimethylformamide. After refluxing for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C, followed by dropwise addition of pyridine 2.38 g (30 mmol). It was. After the addition was completed, the same procedure as in Example 1 was carried out to obtain 1.56 g (4.9 mmol; yield 49%) of the title compound.
합성synthesis
2-알릴아미노-4-에틸-티아졸-5-카르복시산 2.12g(10mmol), 디클로로메탄 20g 및 N,N-디메틸포름아미드 0.1g을 교반하면서 실온에서 티오닐 클로라이드 1.43g (12mmol)을 적가한 후 2시간동안 환류시켰다. 그 후 10g의 용매를 감압증류하고 잔류용액의 온도를 0 내지 5℃사이로 유지하면서 아미노-티오펜-2-일-아세토니트릴 염산염 1.75g(10mmol)을 투입한 후 피리딘 2.38g(30mmol)을 적가하였다. 적가가 완료된 후 실시예 1에서와 동일하게 실시하여 표제화합물 1.90g(5.7mmol; 수율 57%)을 수득하였다.2.12 g (10 mmol) of 2-allylamino-4-ethyl-thiazole-5-carboxylic acid, 20 g of dichloromethane and 0.1 g of N, N-dimethylformamide were added dropwise to 1.43 g (12 mmol) of thionyl chloride at room temperature with stirring. It was then refluxed for 2 hours. Thereafter, 10 g of a solvent was distilled under reduced pressure, and 1.75 g (10 mmol) of amino-thiophen-2-yl-acetonitrile hydrochloride was added while maintaining the temperature of the remaining solution between 0 and 5 ° C, followed by dropwise addition of pyridine 2.38 g (30 mmol). It was. After the dropwise addition was completed in the same manner as in Example 1 to obtain 1.90 g (5.7 mmol; yield 57%) of the title compound.
상기 설명한 바와 같은 본 발명의 방법에 따라 화학식 1로 표시되는 2-아미노티아졸카르복사미드 유도체를 제조하게 되면 고순도의 목적화합물을 고수율로 제조할 수 있을 뿐아니라, 본 발명에 따른 방법은 기존의 방법에 비하여 보다 간편하고 경제적일 것으로 기대된다.When the 2-aminothiazolecarboxamide derivative represented by Chemical Formula 1 is prepared according to the method of the present invention as described above, it is possible to prepare a high purity target compound in high yield. It is expected to be simpler and more economical than the method.
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019970024120A KR100212635B1 (en) | 1997-06-11 | 1997-06-11 | Process for preparation of 2-aminothiazolecarboxamide derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019970024120A KR100212635B1 (en) | 1997-06-11 | 1997-06-11 | Process for preparation of 2-aminothiazolecarboxamide derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR19990000959A true KR19990000959A (en) | 1999-01-15 |
| KR100212635B1 KR100212635B1 (en) | 1999-08-02 |
Family
ID=19509216
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019970024120A KR100212635B1 (en) | 1997-06-11 | 1997-06-11 | Process for preparation of 2-aminothiazolecarboxamide derivatives |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR100212635B1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100420758B1 (en) * | 2000-11-23 | 2004-03-02 | 주식회사 엘지생명과학 | Photostabilized Fungicide That Contains Ethaboxam and its Photostabilizer, Method for Fungicidal Use and Method for Increasing Photostability of Ethaboxam |
| KR100426179B1 (en) * | 2000-05-10 | 2004-04-03 | 주식회사 엘지생명과학 | Novel fungicidal compositions containing N-(α-cyano-2-thenyl)-4-ethyl-2-(ethylamino)-5-thiazolecarboxamide |
| KR101142283B1 (en) * | 2005-03-11 | 2012-05-07 | 스미또모 가가꾸 가부시끼가이샤 | Novel Process For Preparation Of 2-Aminothiazole Carboxamide Derivatives |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20000021443A (en) | 1998-09-29 | 2000-04-25 | 성재갑 | Method for preparing 2-aminothiazole carboxamide derivatives |
-
1997
- 1997-06-11 KR KR1019970024120A patent/KR100212635B1/en not_active IP Right Cessation
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100426179B1 (en) * | 2000-05-10 | 2004-04-03 | 주식회사 엘지생명과학 | Novel fungicidal compositions containing N-(α-cyano-2-thenyl)-4-ethyl-2-(ethylamino)-5-thiazolecarboxamide |
| KR100420758B1 (en) * | 2000-11-23 | 2004-03-02 | 주식회사 엘지생명과학 | Photostabilized Fungicide That Contains Ethaboxam and its Photostabilizer, Method for Fungicidal Use and Method for Increasing Photostability of Ethaboxam |
| KR101142283B1 (en) * | 2005-03-11 | 2012-05-07 | 스미또모 가가꾸 가부시끼가이샤 | Novel Process For Preparation Of 2-Aminothiazole Carboxamide Derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| KR100212635B1 (en) | 1999-08-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5285652B2 (en) | Chemical synthesis of morpholine derivatives | |
| CZ292123B6 (en) | Process for preparing mofetil mycophenolate | |
| EP1362040B1 (en) | Process for the preparation of mesylates of piperazine derivatives | |
| KR100212635B1 (en) | Process for preparation of 2-aminothiazolecarboxamide derivatives | |
| US4032559A (en) | N,2-dicyanoacetimidates | |
| AU2002250962A1 (en) | Process for the preparation of mesylates of piperazine derivatives | |
| CA1271769A (en) | 4-alkoxy-3-pyrrolin-2-on-1-yl acetic acid alkyl esters and their production | |
| US4769465A (en) | Process for the preparation of 2-(N-benzyl-N-methylamino)-ethyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate and its hydrochloride salt | |
| US4925944A (en) | Process for the preparation of o-carboxypyridyl- and o-carboxyquinolylimidazolinones | |
| US4160828A (en) | Analgesic phosphinyl compounds and compositions | |
| CN111875557B (en) | Thiazole derivative and synthesis method thereof | |
| CA2083977A1 (en) | Pyrroline n-oxide derivatives | |
| JP2023548681A (en) | New synthesis of L-phenylalanine amide | |
| US5322948A (en) | Process for preparing pyridinecarboxylic acid derivatives | |
| KR100302347B1 (en) | A process for preparing nizatidine | |
| KR100354806B1 (en) | New intermediate for the preparation of amlodipine besylate and its process | |
| Yarovenko et al. | Reactions of monothiooxamides with N-nucleophiles. Synthesis of 4, 5-dihydroimidazole-2-carboxanilides | |
| KR970011450B1 (en) | Process of preparation of n-alkyl-n-arylcarbamoyl chloride | |
| KR101142283B1 (en) | Novel Process For Preparation Of 2-Aminothiazole Carboxamide Derivatives | |
| KR100209068B1 (en) | Method for the preparation of coumarin dyes | |
| KR900007314B1 (en) | Process for preparing n-(methoxyacetyl)-n-(2,l-dimethyl phenyl)-o-amino-oxazolidine-2-one | |
| US6706883B1 (en) | Process for producing (8-chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-B]pyridin-11-YL)-1-piperdine | |
| JP2000281636A (en) | Production of active methylene-substituted arene derivative | |
| JPH05202046A (en) | Pyrimidopteridine derivative and its production | |
| JP2001278864A (en) | Method for producing 4-methoxyquinolines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment | ||
| FPAY | Annual fee payment | ||
| FPAY | Annual fee payment |
Payment date: 20170327 Year of fee payment: 19 |
|
| EXPY | Expiration of term |