公开(公告)号：KR100418915B1

公开(公告)日：2004-02-14

申请号：KR1020000071399

申请日：2000-11-28

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  조용서 ,  최경일 ,  배애님 ,  강경호 ,  이희윤 ,  손정훈 ,  공재양 ,  정대영

IPC: C07D401/04

Abstract: PURPOSE: A 4-aminopiperidine analogue and a producing method thereof are provided, therefore the compound can be useful as a ligand of a muscarine receptor, and it is thus used in study on Alzheimer disease. CONSTITUTION: The 4-aminopiperidine analogue is represented by formula(I), wherein R1, R2, R3, R4, R5, R6 and R7 are hydrogen, cycloalkyl having carbon number of 1 to 6, alkoxy, halogen, hydroxy, hydroxymethyl, aryl, heteroaryl, amino, alkylamino, alkenyl, carbonyl or hetero ring having carbon number of 5 to 7 wherein aryl is a ring having 6 atoms, two rings having 10 atoms or a stable resonance form having double bond to adjacent carbon; heteroaryl is a single ring aromatic group having carbon number of 5 to 6 or a double ring aromatic group having carbon number of 10 in which the heteroaryl has at least one hetero atom of N, O or S; hetero ring consists of 5 to 7 atoms having 1 to 3 of N, O or S; X is carbon or sulfur; and n is an integer of 1 to 2 wherein n is 1 when X is carbon and is 2 when X is sulfur. The 4-aminopiperidine analogue is produced by reacting piperidine or amine(II) with piperazine with ketone(III) in the presence of 1 to 3 equivalent of acetic acid, 2 to 10 equivalent of reducing agent and solvent at room temperature for 3 to 24 hours to produce 4-aminopiperidine(I) and adding NaHCO3 solution and organic solvent to 4-aminopiperidine(I); and drying the extracted 4-aminopiperidine(I), dissolving it, adding 1 to 10 equivalent of hydrogen chloride to the solution, and separating, washing and drying the hydrochloride of 4-aminopiperidine.

Abstract translation: 目的：提供了4-氨基哌啶类似物及其生产方法，因此该化合物可用作毒蕈碱受体的配体，因此用于研究阿尔茨海默病。 构成：4-氨基哌啶类似物由式（I）表示，其中R1，R2，R3，R4，R5，R6和R7是氢，碳数为1-6的环烷基，烷氧基，卤素，羟基，羟甲基，芳基 杂芳基，氨基，烷基氨基，链烯基，羰基或杂环，其中芳基是具有6个原子的环，具有10个原子的两个环或具有与相邻碳双键的稳定的共振形式; 杂芳基为碳数为5至6的单环芳族基团或碳数为10的双环芳族基团，其中杂芳基具有至少一个N，O或S的杂原子; 杂环由5至7个具有1至3个N，O或S的原子组成; X是碳或硫; 并且n是1至2的整数，其中当X是碳时，n是1，当X是硫时，n是2。 4-氨基哌啶类似物是通过使哌啶或胺（II）与哌嗪与酮（III）在1至3当量乙酸，2至10当量还原剂和溶剂的存在下在室温下反应3至24 小时以产生4-氨基哌啶（I）并将NaHCO 3溶液和有机溶剂加入到4-氨基哌啶（I）中; 干燥提取的4-氨基哌啶（I），溶解，加入1至10当量的氯化氢至溶液中，分离，洗涤并干燥4-氨基哌啶的盐酸盐。

公开(公告)号：KR100466797B1

公开(公告)日：2005-01-24

申请号：KR1020010089276

申请日：2001-12-31

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  고훈영 ,  배애님 ,  강경호 ,  김상희

IPC: C07D223/16

Abstract: PURPOSE: Benzoazepine derivatives and a preparation process thereof using indium are provided, thereby rapidly and easily preparing the benzoazepine derivatives using an appropriate amount of indium powder. CONSTITUTION: Benzoazepine derivatives are represented by the formula IV, wherein X is H, F, Cl, Br, I, alkyl or alkoxy. The benzoazepine derivatives represented by the formula III are also provided, wherein R is methyl, ethyl or hydrogen; and X is H, F, Cl, Br, I, alkyl or alkoxy. A process for preparing benzoazepine derivatives of the formula IV comprises the steps of: (1) stirring 2-nitro benzaldehyde derivatives of the formula I and methyl 2-(bromomethyl) acrylate or ethyl 2-(bromomethyl) acrylate in water or aqueous organic solvent, together with indium coil or indium thin layer and acid to prepare a compound of the formula III; and (2) reacting the compound of the formula III with base in an organic solvent, wherein the aqueous organic solvent in the step (1) is tetrahydrofuran solution, acetonitrile solution, N,N-dimethylformamide solution, methylalcohol solution or ethylalcohol solution; the base in the step (2) is sodium hydride, potassium butoxide, sodium bicarbonate, sodium carbonate, potassium carbonate or cesium carbonate; and the organic solvent in the step (2) is tetrahydrofuran, N,N-dimethylformamide, methylsulfoxide, dimethylsulfoxide or dichloromethane.

Abstract translation: 目的：提供苯并氮杂衍生物及其使用铟的制备方法，由此使用适量的铟粉迅速且容易地制备苯并吖庚因衍生物。 构成：苯并氮杂衍生物由式Ⅳ表示，其中X是H，F，Cl，Br，I，烷基或烷氧基。 还提供了由式III表示的苯并吖庚因衍生物，其中R是甲基，乙基或氢; X是H，F，Cl，Br，I，烷基或烷氧基。 制备式Ⅳ的苯并吖庚因衍生物的方法包括以下步骤：（1）将式I的2-硝基苯甲醛衍生物和2-（溴甲基）丙烯酸甲酯或2-（溴甲基）丙烯酸乙酯在水或含水有机溶剂 与铟线圈或铟薄层和酸一起制备式III的化合物; （2）使式III化合物与碱在有机溶剂中反应，其中步骤（1）中的含水有机溶剂为四氢呋喃溶液，乙腈溶液，N，N-二甲基甲酰胺溶液，甲醇溶液或乙醇溶液; 步骤（2）中的碱为氢化钠，丁醇钾，碳酸氢钠，碳酸钠，碳酸钾或碳酸铯; 步骤（2）中的有机溶剂为四氢呋喃，N，N-二甲基甲酰胺，甲基亚砜，二甲基亚砜或二氯甲烷。

公开(公告)号：KR100373485B1

公开(公告)日：2003-02-25

申请号：KR1019990041612

申请日：1999-09-28

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  조용서 ,  최경일 ,  배애님 ,  강경호 ,  이희윤

IPC: C07D295/22

Abstract: PURPOSE: Provided is a novel isooxazol piperazin derivative which is used as an antagonist against dopamine-1 receptor related to the central nerve system disorders. CONSTITUTION: A novel isooxazol piperazin derivative represented by the formula (1) is manufactured by reacting secondary amine of the formula (2) with aldehyde of the formula (3) in the presence of NaBh(OAc)3, NaBH3CN, or NaBH4 as a reductant and methylene chloride as a solvent at room temperature for 3-24 hours, preferably 12-14 hours. In the formula (1), n is an integer of between 1 and 4; R1 is a phenyl group at an ortho, meta, or para position substituted by more than one group among halogen, trifluoromethyl, -NO2, alkyl group of C1-C3 , and alkoxy group of C1-C3, or an alkyl group of C1-C3, hydroxy group, 4-(2-keto-1-benzimidazolerynyl), 1-(2-(trifluoromethyl)benzene, 4-(4-chlorophenyl)-4-hydroxy, 1-(2-pyrimidyl), or 1-benzyl group; R2-R5 is hydrogen; R6 is a phenyl group at an ortho, meta, or para position substituted by more than one group among halogen group, trifluoromethyl group , -CN, -NO2, an alkyl group of C1-C3, phenoxy group, and alkoxy group of C1-C3 and an unsaturated 5 or 6 hetero ring group having more than one atom from an alkyl group of C-C3, alkoxy group of C1-C3, thiophenyl group, (2-phenyl)vinyl group, pyridyl group, and from oxygen, sulfur, and nitrogen; and Q is isoxazol (A) or 4,5-dihydroisoxazole derivative (B).

Abstract translation: 用途：提供了一种新的异恶唑哌嗪衍生物，其用作针对与中枢神经系统疾病相关的多巴胺-1受体的拮抗剂。 结构式（1）表示的新型异恶唑哌嗪衍生物是通过使式（2）的仲胺与式（3）的醛在NaBh（OAc）3，NaBH3CN或NaBH4存在下反应制备的 还原剂和二氯甲烷作为溶剂在室温下反应3-24小时，优选12-14小时。 式（1）中，n为1〜4的整数， R 1是在卤素，三氟甲基，-NO 2，C 1 -C 3的烷基和C 1 -C 3的烷氧基中的多于一个基团取代的邻位，间位或对位的苯基，或者C1- C3-羟基，4-（2-酮-1-苯并咪唑基），1-（2-（三氟甲基）苯，4-（4-氯苯基）-4-羟基，1-（2-嘧啶基） 苄基; R 2 -R 5是氢; R 6是在卤素基团，三氟甲基，-CN，-NO 2，C 1 -C 3烷基，C 1 -C 3烷氧基， 苯氧基和C 1 -C 3的烷氧基以及具有超过一个来自C 1 -C 3的烷基，C 1 -C 3的烷氧基，噻吩基，（2-苯基）乙烯基的不饱和5或6个杂环基 ，吡啶基和氧，硫和氮;并且Q是异恶唑（A）或4,5-二氢异恶唑衍生物（B）。

公开(公告)号：KR1020030058742A

公开(公告)日：2003-07-07

申请号：KR1020010089276

申请日：2001-12-31

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  고훈영 ,  배애님 ,  강경호 ,  김상희

IPC: C07D223/16

Abstract: PURPOSE: Benzoazepine derivatives and a preparation process thereof using indium are provided, thereby rapidly and easily preparing the benzoazepine derivatives using an appropriate amount of indium powder. CONSTITUTION: Benzoazepine derivatives are represented by the formula IV, wherein X is H, F, Cl, Br, I, alkyl or alkoxy. The benzoazepine derivatives represented by the formula III are also provided, wherein R is methyl, ethyl or hydrogen; and X is H, F, Cl, Br, I, alkyl or alkoxy. A process for preparing benzoazepine derivatives of the formula IV comprises the steps of: (1) stirring 2-nitro benzaldehyde derivatives of the formula I and methyl 2-(bromomethyl) acrylate or ethyl 2-(bromomethyl) acrylate in water or aqueous organic solvent, together with indium coil or indium thin layer and acid to prepare a compound of the formula III; and (2) reacting the compound of the formula III with base in an organic solvent, wherein the aqueous organic solvent in the step (1) is tetrahydrofuran solution, acetonitrile solution, N,N-dimethylformamide solution, methylalcohol solution or ethylalcohol solution; the base in the step (2) is sodium hydride, potassium butoxide, sodium bicarbonate, sodium carbonate, potassium carbonate or cesium carbonate; and the organic solvent in the step (2) is tetrahydrofuran, N,N-dimethylformamide, methylsulfoxide, dimethylsulfoxide or dichloromethane.

Abstract translation: 目的：提供苯并氮杂衍生物及其使用铟的制备方法，由此使用适量的铟粉快速且容易地制备苯并氮杂衍生物。 构成：苯并氮杂衍生物由式IV表示，其中X是H，F，Cl，Br，I，烷基或烷氧基。 还提供了由式III表示的苯并氮杂衍生物，其中R是甲基，乙基或氢; 且X为H，F，Cl，Br，I，烷基或烷氧基。 制备式Ⅳ的苯并吖庚因衍生物的方法包括以下步骤：（1）将式I的2-硝基苯甲醛衍生物和2-（溴甲基）丙烯酸甲酯或2-（溴甲基）丙烯酸乙酯在水或含水有机溶剂中搅拌 ，与铟线圈或铟薄层和酸一起制备式III化合物; 和（2）使式III化合物与碱在有机溶剂中反应，其中步骤（1）中的有机有机溶剂是四氢呋喃溶液，乙腈溶液，N，N-二甲基甲酰胺溶液，甲醇溶液或乙醇溶液; 步骤（2）中的碱为氢化钠，丁醇钾，碳酸氢钠，碳酸钠，碳酸钾或碳酸铯; 并且步骤（2）中的有机溶剂是四氢呋喃，N，N-二甲基甲酰胺，甲基亚砜，二甲基亚砜或二氯甲烷。

公开(公告)号：KR1020030058741A

公开(公告)日：2003-07-07

申请号：KR1020010089275

申请日：2001-12-31

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  김유승 ,  고훈영 ,  최경일 ,  강경호 ,  배애님

IPC: C07D209/36

Abstract: PURPOSE: Indol derivatives and a preparation process thereof are provided, thereby rapidly preparing indol derivatives under mild conditions in higher yield. CONSTITUTION: Indol derivatives are represented by the formula 6, wherein R is H, or halogen selected from Cl, F, Br and I; and Y is -Ts(tosyl), -Ms(mesyl) or -Ac(acetyl). A process for preparing the indol derivatives of the formula 6 comprises the steps of: reacting a compound of the formula 1 with a compound of the formula 2 in the presence of indium metal and acid to simultaneously perform allylation of aldehyde and reduction of nitro group, thereby preparing a compound of the formula 3; protecting amine group of the compound of the formula 3 to prepare a compound of the formula 4; oxidizing secondary alcohol of the compound of the formula 4 to prepare a compound of the formula 5; and cyclization of the compound of the formula 5 in the presence of organic base, wherein the oxidation of secondary alcohol uses pyridinium chlorochromate(PCC) or pyridinium dichromate(PDC) or Swern's oxidation or Dess-Martin periodinane oxidation; and the organic base is diisopropylethylamine, DBU (1,8-diazabicyclo£5.4.0|undec-7-ene), DBN (1,5-diazabicyclo£4.3.0|non-5-ene), triethylamine or pyridine.

Abstract translation: 目的：提供吲哚衍生物及其制备方法，从而在温和条件下以更高的收率快速制备吲哚衍生物。 构成：吲哚衍生物由式6表示，其中R是H，或选自Cl，F，Br和I的卤素; 和Y是-T（甲苯磺酰基），-Ms（甲磺酰）或-Ac（乙酰基）。 制备式6的吲哚衍生物的方法包括以下步骤：在铟金属和酸的存在下使式1的化合物与式2的化合物反应，以同时进行醛的还原和烯基的还原， 从而制备式3的化合物; 保护式3化合物的胺基以制备式4的化合物; 氧化式4化合物的仲醇制备式5的化合物; 在有机碱的存在下环化式5的化合物，其中仲醇的氧化使用氯铬酸吡啶鎓（PCC）或重铬酸吡啶鎓（PDC）或Swern的氧化或Dess-Martin氧化氧化; 有机碱是二异丙基乙胺，DBU（1,8-二氮杂双环{5.4.0 |十一-7-烯），DBN（1,5-二氮杂双环{4.3.0 |非-5-烯），三乙胺或吡啶。

公开(公告)号：KR100488444B1

公开(公告)日：2005-05-11

申请号：KR1020010089274

申请日：2001-12-31

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  김유승 ,  고훈영 ,  최경일 ,  강경호 ,  배애님

IPC: C07D215/56

Abstract: 다음 화학식 6의 헤테로고리 화합물 및 그의 제조 방법;
화학식 6

식 중에서, R은 H이거나 Cl, F, Br 및 I에서 선택되는 할로겐 원소이고; R
1 와 R
2 는 서로 독립적으로 H, 알킬기 또는 -OH기이며, Y는 -Ts(토실), -Ms(메실) 또는 -Ac(아세틸)임.

公开(公告)号：KR100451414B1

公开(公告)日：2004-10-06

申请号：KR1020010089275

申请日：2001-12-31

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  김유승 ,  고훈영 ,  최경일 ,  강경호 ,  배애님

IPC: C07D209/36

Abstract: PURPOSE: Indol derivatives and a preparation process thereof are provided, thereby rapidly preparing indol derivatives under mild conditions in higher yield. CONSTITUTION: Indol derivatives are represented by the formula 6, wherein R is H, or halogen selected from Cl, F, Br and I; and Y is -Ts(tosyl), -Ms(mesyl) or -Ac(acetyl). A process for preparing the indol derivatives of the formula 6 comprises the steps of: reacting a compound of the formula 1 with a compound of the formula 2 in the presence of indium metal and acid to simultaneously perform allylation of aldehyde and reduction of nitro group, thereby preparing a compound of the formula 3; protecting amine group of the compound of the formula 3 to prepare a compound of the formula 4; oxidizing secondary alcohol of the compound of the formula 4 to prepare a compound of the formula 5; and cyclization of the compound of the formula 5 in the presence of organic base, wherein the oxidation of secondary alcohol uses pyridinium chlorochromate(PCC) or pyridinium dichromate(PDC) or Swern's oxidation or Dess-Martin periodinane oxidation; and the organic base is diisopropylethylamine, DBU (1,8-diazabicyclo£5.4.0|undec-7-ene), DBN (1,5-diazabicyclo£4.3.0|non-5-ene), triethylamine or pyridine.

Abstract translation: 目的：提供吲哚衍生物及其制备方法，由此在温和条件下以较高的产率快速制备吲哚衍生物。 构成：吲哚衍生物由式6表示，其中R是H或选自Cl，F，Br和I的卤素; Y是-Ts（甲苯磺酰基），-Ms（甲磺酰基）或-Ac（乙酰基）。 制备式6吲哚衍生物的方法包括以下步骤：使式1化合物与式2化合物在铟金属和酸存在下反应，同时进行醛的烯丙基化和硝基的还原， 由此制备式3的化合物; 保护式3化合物的胺基以制备式4化合物; 氧化式4化合物的仲醇以制备式5化合物; 在有机碱存在下环化式5化合物，其中仲醇的氧化使用氯铬酸吡啶鎓（PCC）或重铬酸吡啶鎓（PDC）或斯文氧化或戴斯 - 马丁氧化剂氧化; DBU（1,8-二氮杂双环〔5.4.0〕十一碳-7-烯），DBN（1,5-二氮杂双环〔4.3.0〕壬-5-烯），三乙胺或吡啶组成的有机碱。

公开(公告)号：KR100355343B1

公开(公告)日：2002-10-12

申请号：KR1019990050823

申请日：1999-11-16

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  조용서 ,  최경일 ,  배애님 ,  강경호 ,  이희윤 ,  공재양 ,  정대영

IPC: C07D261/14

Abstract: 본발명은신규삼차아미노에틸이소옥사졸유도체및 그제조방법에관한것으로서, 상기이소옥사졸유도체는여러가지중추신경계장애와관련이있는도파민-1 수용체의길항제로서작용하며, 그구조는화학식 1과같다. [화학식 1] 그제조방법은아래의화학식 2의아민과화학식 3의토실레이트의치환반응을이용한것으로서, 그반응은반응식 1과같다. [화학식 2] [화학식 3] [반응식 1] 상기화학식 1, 2, 3 및반응식 1에서, R는페닐, 할로겐원자에의해치환된페닐, 트리플루오로메틸에의해치환된페닐, 페닐기의 2, 3 또는 4 위치에트리플루오로메틸에의해치환된페닐메틸, 디페닐메틸, 페닐기의 2, 3 또는 4 위치에할로겐원자에의해치환된디페닐메틸, 벤질, 3-히드로벤즈이미다졸-2-온이며; R내지 R는모두수소이며; R는니트로기, 페녹시기, 메톡시기, 트리플루오로메틸기및 할로겐기로구성되는군에서선택되는하나이상에의해치환된페닐, 페닐기에의해치환된비닐또는 O, S 및 N으로구성되는군에서선택되는한가지원자에의해치환된 5환또는 6환의불포화또는포화헤테로고리화합물이며; X는질소또는 C-H이다.

公开(公告)号：KR100349035B1

公开(公告)日：2002-08-17

申请号：KR1020000037558

申请日：2000-07-01

Applicant: 한국과학기술연구원

Inventor： 조용서 ,  김유승 ,  고훈영 ,  최경일 ,  강경호

IPC: C07C209/32

Abstract: 본 발명은 인듐 금속 및 산을 이용하여 알데히드(-CHO)의 알릴화 및 니트로기(-NO
2 )의 환원 반응을 동시에 행하는 방법에 관한 것이며, 보다 구체적으로는 화학식
1의 화합물을 인듐 금속 및 산의 존재하에 화학식 2의 화합물과 반응시켜 알데히드의 알릴화 반응과 니트로기(-NO
2 )의 아민기(-NH
2 )로의 환원 반응을 동시에 행하여 화학식 3의 화합물을 제조하는 방법에 관한 것이다(반응식 1).
화학식 1

화학식 2

화학식 3

반응식 1

상기 화학식 1 내지 3 및 반응식 1 중에서, R은 C
6 -C
10 방향족 고리를 말하며; R
1 -R
3 은 서로 독립적으로 수소, C
1 -C
6 알킬기, 페닐기 또는 C
1 -C
3 알콕시 카르보닐기를 말하며; k는 0 - 4이며, 각 치환체 Y는 할로겐, 할로겐에 의해 치환된 또는 비치환된 C
1 -C
3 알킬기, 또는 할로겐에 의해 치환된 또는 비치환된 C
1 -C
3 알콕시기이거나, 두 개의 Y가 조합하여 5원 또는 6원 고리 또는 헤테로고리를 형성할 수 있으며; m은 1 - 3이며, n은 1 - 3이며; X은 Cl, Br, I로 구성되는 군에서 선택되는 할로겐 원소를 말한다.
상기 제조방법은 종래의 방법에 비해 알데히드의 알릴화 반응과 니트로기의 환원 반응을 동시에 수행할 수 있으며, 반응 수율이 높고, 반응이 상온에서 짧은 시간내에 진행하고, 수용액 상에서 반응이 손쉽게 진행되므로 환경친화적인 산업공정이다는 장점이 있다.

公开(公告)号：KR100343948B1

公开(公告)日：2002-07-24

申请号：KR1019990050824

申请日：1999-11-16

Applicant: 한국과학기술연구원

Inventor： 고훈영 ,  조용서 ,  최경일 ,  배애님 ,  강경호 ,  이희윤

IPC: C07D403/02

Abstract: 본발명은화학식 1을갖는이소옥사졸피페라진계열의화합물또는그의허용되는염 및그 제조방법과관한것으로, 상기화합물은아래의화학식 1을갖고, 그제조방법은아래의화학식 2의화합물과화학식 3의화합물을 1,3-쌍극자고리화첨가반응시키는것으로구성된다. 본발명은또한상기제조방법을용액상조합합성에응용하여제조된라이브러리에관한것이다. [화학식 1] [화학식 2] [화학식 3] 상기화학식 1, 2 및 3에서 R은 C-C의방향족탄화수소, C-C의알킬기에의해치환된 C-C의방향족탄화수소, C-C의알콕시기에의해치환된 C-C의방향족탄화수소, 할로겐에의해치환된 C-C의방향족탄화수소또는 C-C의아릴알킬이며; R-R는서로독립적으로수소, 할로겐, 메틸또는에틸이며; R-R은서로독립적으로수소, 할로겐에의해치환된페녹시, -OC(O)R, -NRR,,또는이며, 상기식 중 Y는 O 또는 S이고, R은 C-C의알킬기이고, R및 R은서로독립적으로 C-C의알킬기이고, R은수소, C-C의알킬기또는페닐이고, R는서로독립적으로수소또는 C-C의알킬기이고, n는 1-2의정수이고, k는 n=1이면 5, n=2이면 6이고, m은 n=1이면 4, n=2이면 5이다.