公开(公告)号：KR100738229B1

公开(公告)日：2007-07-12

申请号：KR1020010088829

申请日：2001-12-31

Applicant: 한국화학연구원

Inventor： 박태호 ,  한철 ,  김선주

IPC: C07D401/02

Abstract: 본 발명은 항생제 제조용 치환체로서 사용되는, 피롤리딘 고리로 치환된 피리딘 유도체에 관한 것으로, 본 발명의 신규한 피리딘 유도체는 퀴놀론계, 퀴놀리진계, 카바페넴계, 페넴계 또는 세팔로스포린계 유도체에 치환체로서 결합되어 우수한 항균작용과 광범위한 항균 스펙트럼을 부여한다.

公开(公告)号：KR1020030042883A

公开(公告)日：2003-06-02

申请号：KR1020010073696

申请日：2001-11-26

Applicant: 한국화학연구원

Inventor： 박태호 ,  이상호 ,  한철 ,  김선주

IPC: C07D207/12

Abstract: PURPOSE: A method of preparing oxiracetam is provided to make oxiracetam product in high purity and yield. The oxiracetam improves brain functions and therapeutic effect on dementia. CONSTITUTION: In a method of preparing oxiracetam of the formula(1), a tri-amide compound of the formula(2) is first prepared by reacting an organic solvent compound of the formula(4) with an organic solvent compound of the formula(5). A compound of the formula(3) is prepared by sequentially conducting cyclization, decarboxylation and reduction with respect to the compound of the formula(2). The compound of the formula(3) reacts with ammonia under the existence of water or alcohol. In the formulae, R is methyl group or ethyl group, and X is hydroxy group or halide. The cyclization of the compound of the formula(2) is achieved by reaction with hydride or alkoxide at -30-50 deg.C for 1-15 hours.

Abstract translation: 目的：提供奥拉西坦的制备方法，以高纯度和高产率制备奥拉西坦产品。 奥拉西坦可改善痴呆症的大脑功能和治疗效果。 构成：在制备式（1）的奥拉西坦的方法中，式（2）的三酰胺化合物首先通过使式（4）的有机溶剂化合物与式（4）的有机溶剂化合物 5）。 式（3）的化合物通过相对于式（2）的化合物依次进行环化，脱羧和还原来制备。 式（3）的化合物在水或醇的存在下与氨反应。 式中，R为甲基或乙基，X为羟基或卤化物。 式（2）化合物的环化通过在-30-50℃与氢化物或醇盐反应1-15小时来实现。

公开(公告)号：KR100351659B1

公开(公告)日：2002-09-05

申请号：KR1020000038153

申请日：2000-07-05

Applicant: 한국화학연구원

Inventor： 박태호 ,  이상호 ,  한철 ,  김선주 ,  성길연 ,  곽형섭

IPC: C07D207/22

Abstract: 본 발명은 3-메톡시이미노-4-아미노메틸피롤리딘 유도체의 개선된 제조방법에 관한 것으로서, 1-벤질-3-옥소-4-에톡시카보닐피롤리딘으로부터 퀴놀론 항균제의 7번 위치의 유용한 치환기로 사용되는 하기 화학식 1의 3-메톡시이미노-4-아미노메틸피롤리딘 유도체를 간편하게 고효율로 제조할 수 있다:

상기 식에서,
R
1 은 수소, C
1-4 알킬기, 또는 아릴 또는 헤테로아릴기로 치환된 C
1-4 알킬기이고;
R
2 는 수소, C
1-4 알킬기, 포르밀기 또는 t-부톡시카보닐기이고;
HX는 유기산 또는 무기산을 나타내고;
n은 1 내지 3의 정수이다.

公开(公告)号：KR100395779B1

公开(公告)日：2003-08-21

申请号：KR1020010028837

申请日：2001-05-25

Applicant: 한국화학연구원

Inventor： 박태호 ,  이상호 ,  한철

IPC: C07D211/42

Abstract: PURPOSE: Provided is a preparation method of secondary amide in high purity and yield from tertiary amide by elimination of β-substituted α-arylalkyl group in reaction with protonic acid in organic solvent. The α-arylethylamine or α-aryl-β-substituted ethylamine is used as a nitrogen source in synthesis of biologically active compounds. CONSTITUTION: The synthesis of the secondary amide is characterized by making a tertiary amide represented by the formula(2) react with protonic acid in organic solvent to manufacture a secondary amine represented by the formula(1) by stirring at 10-150 deg.C for 2-24 hours. In the formulae, R1 is C1-5 alkyl, C3-7cycloalkyl, heterocyclic or C6-15 aryl group substituted with one or more groups selected from low alkyl with C1-4, hydroxy, animo, halogen, alkoxy, monoalkylamino, dialkylamino and carboxyl group; R2 is C1-5 alkyl group substituted with more than one group selected from amino, hydroxy, mono alkylamino, alkoxy and halogen; Ar is phenyl or α- or β-naphthyl group substituted by one or more groups selected from halogen, methoxy, carbamoyl, sulfamoyl, nitro group; R3 is C6-15 alkyl, phenyl or heterocyclic group substituted by one or more groups selected from C1-4 low alkyl, hydroxy, amino, halogen, alkoxy, mon alkylamino, dialkyl amino, carboxyl, carbamoyl, sulfamoyl, nitro or cyano group; and R1 and R3 are connected to form a 5 or 6 membered ring. The protonic acid is selected from hydrochloric acid, acetic acid, trifluoroacetic acid and methanesulfonic acid.

Abstract translation: 目的：提供一种高纯度仲酰胺的制备方法，该方法通过在有机溶剂中与质子酸反应，消除β-取代的α-芳基烷基，由叔酰胺得到。 α-芳基乙胺或α-芳基-β-取代的乙胺用作合成生物活性化合物的氮源。 构成：仲酰胺的合成的特征在于，使式（2）所示的叔酰胺与质子酸在有机溶剂中反应，在10〜150℃下搅拌制造式（1）所示的仲胺 持续2-24小时。 在通式中，R 1是被一个或多个选自低级烷基和C 1-4羟基，氨基，卤素，烷氧基，单烷基氨基，二烷基氨基和羧基的基团取代的C 1-5烷基，C 3-7环烷基，杂环基或C 6-15芳基 组; R2是被选自氨基，羟基，一烷基氨基，烷氧基和卤素的多于一个基团取代的C1-5烷基; Ar是被一个或多个选自卤素，甲氧基，氨基甲酰基，氨磺酰基，硝基的基团取代的苯基或α-或β-萘基; R 3为C 6-15烷基，苯基或被一个或多个选自C 1-4低级烷基，羟基，氨基，卤素，烷氧基，单烷基氨基，二烷基氨基，羧基，氨基甲酰基，氨磺酰基，硝基或氰基的基团取代的杂环基; 并且R1和R3连接形成5或6元环。 质子酸选自盐酸，乙酸，三氟乙酸和甲磺酸。

公开(公告)号：KR1020020089873A

公开(公告)日：2002-11-30

申请号：KR1020010028837

申请日：2001-05-25

Applicant: 한국화학연구원

Inventor： 박태호 ,  이상호 ,  한철

IPC: C07D211/42

Abstract: PURPOSE: Provided is a preparation method of secondary amide in high purity and yield from tertiary amide by elimination of β-substituted α-arylalkyl group in reaction with protonic acid in organic solvent. The α-arylethylamine or α-aryl-β-substituted ethylamine is used as a nitrogen source in synthesis of biologically active compounds. CONSTITUTION: The synthesis of the secondary amide is characterized by making a tertiary amide represented by the formula(2) react with protonic acid in organic solvent to manufacture a secondary amine represented by the formula(1) by stirring at 10-150 deg.C for 2-24 hours. In the formulae, R1 is C1-5 alkyl, C3-7cycloalkyl, heterocyclic or C6-15 aryl group substituted with one or more groups selected from low alkyl with C1-4, hydroxy, animo, halogen, alkoxy, monoalkylamino, dialkylamino and carboxyl group; R2 is C1-5 alkyl group substituted with more than one group selected from amino, hydroxy, mono alkylamino, alkoxy and halogen; Ar is phenyl or α- or β-naphthyl group substituted by one or more groups selected from halogen, methoxy, carbamoyl, sulfamoyl, nitro group; R3 is C6-15 alkyl, phenyl or heterocyclic group substituted by one or more groups selected from C1-4 low alkyl, hydroxy, amino, halogen, alkoxy, mon alkylamino, dialkyl amino, carboxyl, carbamoyl, sulfamoyl, nitro or cyano group; and R1 and R3 are connected to form a 5 or 6 membered ring. The protonic acid is selected from hydrochloric acid, acetic acid, trifluoroacetic acid and methanesulfonic acid.

Abstract translation: 目的：提供高纯度的仲酰胺的制备方法，通过在有机溶剂中与质子酸反应除去β-取代的α-芳烷基，由叔酰胺得到。 在生物活性化合物的合成中使用α-芳基乙胺或α-芳基-β-取代的乙胺作为氮源。 构成：仲酰胺的合成的特征在于使式（2）表示的叔酰胺与有机溶剂中的质子酸反应，通过在10-150℃下搅拌制造式（1）表示的仲胺 2-24小时。 在式中，R 1是被一个或多个选自具有C 1-4，羟基，脒，卤素，烷氧基，单烷基氨基，二烷基氨基和羧基的低级烷基取代的C 1-5烷基，C 3-7环烷基，杂环基或C 6-15芳基 组; R2是被多于一个选自氨基，羟基，单烷基氨基，烷氧基和卤素的基团取代的C1-5烷基; Ar是被一个或多个选自卤素，甲氧基，氨基甲酰基，氨磺酰基，硝基的基团取代的苯基或α-或β-萘基; R3是被一个或多个选自C1-4低级烷基，羟基，氨基，卤素，烷氧基，一个烷基氨基，二烷基氨基，羧基，氨基甲酰基，氨磺酰基，硝基或氰基的基团取代的C 6-15烷基，苯基或杂环基。 R1和R3连接形成5或6元环。 质子酸选自盐酸，乙酸，三氟乙酸和甲磺酸。

公开(公告)号：KR100424393B1

公开(公告)日：2004-03-24

申请号：KR1020010073696

申请日：2001-11-26

Applicant: 한국화학연구원

Inventor： 박태호 ,  이상호 ,  한철 ,  김선주

IPC: C07D207/12

Abstract: PURPOSE: A method of preparing oxiracetam is provided to make oxiracetam product in high purity and yield. The oxiracetam improves brain functions and therapeutic effect on dementia. CONSTITUTION: In a method of preparing oxiracetam of the formula(1), a tri-amide compound of the formula(2) is first prepared by reacting an organic solvent compound of the formula(4) with an organic solvent compound of the formula(5). A compound of the formula(3) is prepared by sequentially conducting cyclization, decarboxylation and reduction with respect to the compound of the formula(2). The compound of the formula(3) reacts with ammonia under the existence of water or alcohol. In the formulae, R is methyl group or ethyl group, and X is hydroxy group or halide. The cyclization of the compound of the formula(2) is achieved by reaction with hydride or alkoxide at -30-50 deg.C for 1-15 hours.

Abstract translation: 目的：提供制备奥拉西坦的方法以制备高纯度奥拉西坦产物。 奥拉西坦改善脑功能和对痴呆的治疗效果。 构成：在制备式（1）的奥拉西坦的方法中，式（2）的三酰胺化合物首先通过使式（4）的有机溶剂化合物与式（2）的有机溶剂化合物 5）。 式（3）的化合物通过对式（2）的化合物依次进行环化，脱羧和还原来制备。 式（3）的化合物在水或醇存在下与氨反应。 式中，R为甲基或乙基，X为羟基或卤素。 式（2）化合物的环化通过在-30-50℃下与氢化物或醇盐反应1-15小时来实现。

公开(公告)号：KR1020020003786A

公开(公告)日：2002-01-15

申请号：KR1020000038153

申请日：2000-07-05

Applicant: 한국화학연구원

Inventor： 박태호 ,  이상호 ,  한철 ,  김선주 ,  성길연 ,  곽형섭

IPC: C07D207/22

Abstract: PURPOSE: Provided is a method for preparing 3-methoxyimino-4-aminomethylpyrrolidine derivatives, which are used as a useful substituent for the position No.7 of quinolone antibiotics, from 1-benzyl-3-oxo-4-ethoxycarbo0nylpyrrolidine. CONSTITUTION: The method comprises the steps of: reacting a compound of the formula(2) with oxoamine compound or its salt to prepare a compound of the formula(3); reducing a compound of the formula(3) to prepare a compound of the formula(4); hydrogenating and amine-protecting the compound of the formula(4) to prepare a compound of the formula(5); sulfonating the compound of the formula(5) to prepare a compound of the formula(6); aminating or azidonating the compound of the formula(6) to prepare a compound of the formula(8a) or a compound of the formula(7) respectively; hydrogenating the compound of the formula(7) to prepare a compound of the formula(8a) or reacting the compound of the formula(6) with amide to prepare a compound of the formula(8b); and reacting the compound of the formula(8a) or (8b) with acid to deprotect amine.

Abstract translation: 目的：提供3-甲氧基亚氨基-4-氨基甲基吡咯烷衍生物作为喹诺酮类抗生素的第7位的有用取代基，由1-苄基-3-氧代-4-乙氧基羰基吡咯烷制备的方法。 方法：该方法包括以下步骤：使式（2）的化合物与氧代胺化合物或其盐反应以制备式（3）的化合物; 还原式（3）的化合物以制备式（4）的化合物; 氢化和胺保护式（4）化合物以制备式（5）化合物; 磺化式（5）化合物以制备式（6）化合物; 胺化或叠氮化式（6）化合物以分别制备式（8a）化合物或式（7）化合物; 氢化式（7）的化合物以制备式（8a）的化合物或使式（6）的化合物与酰胺反应以制备式（8b）的化合物; 并使式（8a）或（8b）的化合物与酸反应以使胺脱保护。

公开(公告)号：KR100463993B1

公开(公告)日：2004-12-30

申请号：KR1020010088822

申请日：2001-12-31

Applicant: 한국화학연구원

Inventor： 박태호 ,  이상호 ,  한철

IPC: C07D471/04

Abstract: PURPOSE: Quinolone type antimicrobial agents and a preparation process thereof are provided, which compounds have improved antimicrobial activity and wide range of antimicrobial spectrum. CONSTITUTION: Quinolone type antimicrobial agents are represented by the formula 1, wherein R1 is C1-4 alkyl, halogen substituted or unsubstituted phenyl, or halogen substituted or unsubstituted C3-6 cycloalkyl; R2 is hydrogen, amino or C1-4 alkyl; R5 is hydrogen, C1-4 alkyl, C1-4 alkyl substituted or unsubstituted amino, or C1-4 alkyl substituted or unsubstituted aminomethyl or aminoethyl; W is nitrogen, CH or CY; Y is halogen, or halogen substituted or unsubstituted C1-4 alkyl or C1-4 alkoxy; and Pyr is 2-, 3- or 4-pyridyl, provided that W and R1 form COCH2CH(CH3), CCH2CH2CH(CH3) or CSCH2CH(CH3) together when W is CH. A process for preparing the quinolone type antimicrobial agents comprises condensation reacting a compound of the formula 2 with a compound of the formula 3, wherein X is halogen; and HA is hydrogen chloride or trifluoroacetic acid.

Abstract translation: 目的：提供喹诺酮类抗菌剂及其制备方法，该化合物具有改善的抗微生物活性和广泛的抗微生物谱。 构成：喹诺酮类抗微生物剂由式1表示，其中R 1是C 1-4烷基，卤素取代或未取代的苯基或卤素取代或未取代的C 3-6环烷基; R2是氢，氨基或C1-4烷基; R5为氢，C1-4烷基，C1-4烷基取代或未取代的氨基或C1-4烷基取代或未取代的氨基甲基或氨基乙基; W是氮，CH或CY; Y是卤素或卤素取代或未取代的C 1-4烷基或C 1-4烷氧基; 并且Pyr是2-，3-或4-吡啶基，条件是当W是CH时，W和R1一起形成COCH2CH（CH3），CCH2CH2CH（CH3）或CSCH2CH（CH3）。 制备喹诺酮类抗微生物剂的方法包括使式2化合物与式3化合物缩合反应，其中X是卤素; HA是氯化氢或三氟乙酸。

公开(公告)号：KR1020030058401A

公开(公告)日：2003-07-07

申请号：KR1020010088829

申请日：2001-12-31

Applicant: 한국화학연구원

Inventor： 박태호 ,  한철 ,  김선주

IPC: C07D401/02

Abstract: PURPOSE: Pyrolidinyl derivatives used as substituents for preparing antimicrobial agents are provided, which compounds confer improved antimicrobial activity and wide range of antimicrobial spectrum to quinolone type, quinolizine type, carbapenem type, penem type or cephalosporin type derivatives when coupled with the antimicrobial agents. CONSTITUTION: Pyrolidinyl derivatives are represented by the formulas 1a, 1b and 1c, wherein R1 is hydrogen, C1-5 alkyl, C1-5 alkyl substituted or unsubstituted amino, or C1-5 alkyl substituted or unsubstituted aminomethyl; R2, R3, R4 and R5 are hydrogen, halogen, C1-5 alkyl, amino, nitro or cyano; HX is hydrochloric acid or trifluoroacetic acid; and n is 0, 2 or 3.

Abstract translation: 目的：提供用作制备抗微生物剂的取代基的吡咯烷基衍生物，当与抗微生物剂偶联时，该化合物赋予喹诺酮型，喹嗪类，碳青霉烯类，penem型或头孢菌素型衍生物更好的抗菌活性和广泛的抗菌谱。 构成：吡咯烷基衍生物由式1a，1b和1c表示，其中R1是氢，C1-5烷基，C1-5烷基取代或未取代的氨基或C1-5烷基取代或未取代的氨基甲基; R 2，R 3，R 4和R 5是氢，卤素，C 1-5烷基，氨基，硝基或氰基; HX是盐酸或三氟乙酸; 并且n为0,2或3。

公开(公告)号：KR1020030058394A

公开(公告)日：2003-07-07

申请号：KR1020010088822

申请日：2001-12-31

Applicant: 한국화학연구원

Inventor： 박태호 ,  이상호 ,  한철

IPC: C07D471/04

Abstract: PURPOSE: Quinolone type antimicrobial agents and a preparation process thereof are provided, which compounds have improved antimicrobial activity and wide range of antimicrobial spectrum. CONSTITUTION: Quinolone type antimicrobial agents are represented by the formula 1, wherein R1 is C1-4 alkyl, halogen substituted or unsubstituted phenyl, or halogen substituted or unsubstituted C3-6 cycloalkyl; R2 is hydrogen, amino or C1-4 alkyl; R5 is hydrogen, C1-4 alkyl, C1-4 alkyl substituted or unsubstituted amino, or C1-4 alkyl substituted or unsubstituted aminomethyl or aminoethyl; W is nitrogen, CH or CY; Y is halogen, or halogen substituted or unsubstituted C1-4 alkyl or C1-4 alkoxy; and Pyr is 2-, 3- or 4-pyridyl, provided that W and R1 form COCH2CH(CH3), CCH2CH2CH(CH3) or CSCH2CH(CH3) together when W is CH. A process for preparing the quinolone type antimicrobial agents comprises condensation reacting a compound of the formula 2 with a compound of the formula 3, wherein X is halogen; and HA is hydrogen chloride or trifluoroacetic acid.

Abstract translation: 目的：提供喹诺酮类抗微生物剂及其制备方法，该化合物具有改善的抗菌活性和广泛的抗菌谱。 组成：喹诺酮类抗微生物剂由式1表示，其中R1为C1-4烷基，卤素取代或未取代的苯基或卤素取代或未取代的C3-6环烷基; R2是氢，氨基或C1-4烷基; R5是氢，C1-4烷基，C1-4烷基取代或未取代的氨基或C1-4烷基取代或未取代的氨基甲基或氨基乙基; W是氮，CH或CY; Y是卤素，或卤素取代或未取代的C 1-4烷基或C 1-4烷氧基; 并且Pyr是2-，3-或4-吡啶基，条件是当W是CH时，W和R 1一起形成COCH 2 CH（CH 3），CCH 2 CH 2 CH（CH 3）或CSCH 2 CH（CH 3）。 制备喹诺酮型抗微生物剂的方法包括使式2化合物与式3化合物缩合反应，其中X为卤素; HA是氯化氢或三氟乙酸。