公开(公告)号：KR1020020017165A

公开(公告)日：2002-03-07

申请号：KR1020000050327

申请日：2000-08-29

Applicant: 한국과학기술원

Inventor： 김용해 ,  김삼민 ,  변일석

IPC: C07F7/18

CPC classification number: C07F7/1804

Abstract: PURPOSE: Provided are a novel (S)-2-t-butyldiphenylsilyloxymethylindoline of the formula(1) and a process for preparing (2S,3S)-2,3-dialkyltartaric acid by pinacol coupling using it as a chiral ligand, thereby producing (2S,3S)-2,3-dialkyltartaric acid in high chemical and optical yields. CONSTITUTION: (S)-2-t-butyldiphenylsilyloxymethylindoline is represented by the formula(1), wherein R is methyl or phenyl, and prepared by the steps of: reducing (S)-indoline-2-carbonic acid into lithium aluminum hydride; reacting it with chloro t-butyldiphenylsilane compound in the presence of imidazole to obtain (S)-2-t-butyldiphenylsilyloxymethylindoline. (2S,3S)-2,3-dialkyltartaric acid is prepared by the steps of: reacting 2-keto carbonic acid with (S)-2-t-butyldiphenylsilyloxymethylindoline(I) in the presence of dicyclohexylcarbodiimide(DDC) to obtain 2-ketoamide(II); pinacol coupling the 2-ketoamide(II) in the presence of hexamethylphosphoamide(HMP) to obtain dialkyltartaric acid derivative; and hydrolyzing the derivative to manufacture (2S,3S)-2,3-dialkyltartaric acid(III).

Abstract translation: 目的：提供式（1）的新型（S）-2-叔丁基二苯基甲硅烷氧基甲基二氢吲哚和通过频哪醇偶联使其作为手性配体制备（2S，3S）-2,3-二烷基酒石酸的方法，从而产生 （2S，3S）-2,3-二烷基酒石酸，具有高的化学和光学收率。 构成：（S）-2-叔丁基二苯基甲硅烷氧基甲基二氢吲哚由式（1）表示，其中R是甲基或苯基，并通过以下步骤制备：将（S） - 二氢吲哚-2-碳酸还原成氢化铝锂; 在咪唑存在下与氯代叔丁基二苯基硅烷化合物反应，得到（S）-2-叔丁基二苯基甲硅烷氧基甲基二氢吲哚。 （2S，3S）-2,3-二烷基酒石酸通过以下步骤制备：在二环己基碳二亚胺（DDC）的存在下，使2-酮基碳酸与（S）-2-叔丁基二苯基甲硅烷氧基甲基二氢吲哚（I）反应，得到2- 酮酰胺（II）; 频烯醇在六甲基磷酰胺（HMP）的存在下偶联2-酮酰胺（II），得到二烷基酒石酸衍生物; 并水解该衍生物制备（2S，3S）-2,3-二烷基酒石酸（III）。

公开(公告)号：KR100204659B1

公开(公告)日：1999-06-15

申请号：KR1019960018134

申请日：1996-05-28

Applicant: 동국제약 주식회사 ,  한국과학기술원

Inventor： 박진규 ,  김용해 ,  김권 ,  박희석 ,  최준영 ,  김성한 ,  변일석

IPC: C07D489/02

CPC classification number: C07D489/12

Abstract: 본 발명은 테바인을 출발물질로 하여 합성된 일반식(Ⅰ)의 진통제 화합물에 관한 것이다.

상기식에서 R은 수소, 메틸, 에틸 또는 시클로프로필이다.

公开(公告)号：KR1019920018034A

公开(公告)日：1992-10-21

申请号：KR1019910003947

申请日：1991-03-12

Applicant: 한국과학기술원

Inventor： 김용해 ,  임병욱 ,  김권

IPC: C07D251/56

Abstract: 내용 없음

公开(公告)号：KR1019900007247B1

公开(公告)日：1990-10-06

申请号：KR1019880001077

申请日：1988-02-05

Applicant: 한국과학기술원

Inventor： 김용해 ,  임상철 ,  박영준

IPC: C07D489/02

Abstract: A process for preparing buprenorphine of formula (I) comprises (A) oxidation of a cyan compound in 30% H2O2 soln. and NaOH soln. to form a urea cpd. (II), (B) reaction of (II) with KOH in the presence of diethyleneglycol to form a amine cpd. (III), (C) reaction of (III) with halomethylcyclopropane in the presence of K2CO3 and organic solvent, (D) reaction of the resultant cpd. with base in organic solvent to form (I). (I) is useful as an analgesic being antagonistic to narcotic addict.

Abstract translation: 制备式（I）的丁丙诺非的方法包括（A）在30％H 2 O 2溶胶中氧化青色化合物。 和NaOH溶液。 形成尿素cpd。 （II），（B）在二甘醇存在下，（II）与KOH的反应形成胺cpd。 （III），（C）在（K 3 CO 3）和有机溶剂存在下，（III）与卤代甲基环丙烷的反应，（D）所得cpd的反应。 用碱在有机溶剂中形成（I）。 （I）可用作与麻醉药成瘾者拮抗的止痛剂。

公开(公告)号：KR1020020017166A

公开(公告)日：2002-03-07

申请号：KR1020000050328

申请日：2000-08-29

Applicant: 한국과학기술원

Inventor： 김용해 ,  김삼민 ,  변일석

IPC: C07F7/18

CPC classification number: C07F7/1804

Abstract: PURPOSE: Provided are a novel (2S,3aS,7aS)-2-(t-butyldiphenylsilyloxymethyl)octahydroindoline of the formula(1) and a process for preparing (2R,3R)-2,3-dialkyltartaric acid by pinacol coupling using it as a chiral ligand, thereby producing (2R,3R)-2,3-dialkyltartaric acid in high chemical and optical yields. CONSTITUTION: (2S,3aS,7aS)-2-(t-butyldiphenylsilyloxymethyl)octahydroindoline is represented by the formula(1), wherein R is methyl or phenyl, and prepared by the steps of: converting (S)-indoline-2-carbonic acid into (S)-indoline-2-carbonic acid ethyl ester using thionyl chloride and ethanol; reducing it by using platinum oxide to obtain (2S,3aS,7aS)-octahydroindole-2-carbonic acid ethyl ester; reducing it by using lithium aluminum hydride; reacting it with chloro t-butyldiphenylsilane acid in the presence of imidazole to obtain (2S,3aS,7aS)-2-(t-butyldiphenylsilyloxymethyl)octahydroindoline. (2R,3R)-2,3-dialkyltartaric acid is prepared by the steps of: reacting 2-keto carbonic acid with (2S,3aS,7aS)-2-(t-butyldiphenylsilyloxymethyl)octahydroindoline(I) in the presence of dicyclohexylcarbodiimide(DDC) to obtain 2-ketoamide(II); pinacol coupling the 2-ketoamide(II) in the presence of hexamethylphosphoamide(HMP) to obtain dialkyltartaric acid derivative; and hydrolyzing the derivative to manufacture (2R,3R)-2,3-dialkyltartaric acid(III).

Abstract translation: 目的：提供式（1）的新型（2S，3aS，7aS）-2-（叔丁基二苯基甲硅烷氧基甲基）八氢二氢吲哚和通过频闪偶联使用其制备（2R，3R）-2,3-二烷基酒石酸的方法 作为手性配体，从而以高的化学和光学收率产生（2R，3R）-2,3-二烷基酒石酸。 构成：（2S，3aS，7aS）-2-（叔丁基二苯基甲硅烷氧基甲基）八氢二氢吲哚由式（1）表示，其中R是甲基或苯基，并通过以下步骤制备：将（S） - 二氢吲哚-2- 使用亚硫酰氯和乙醇将碳酸转化成（S） - 二氢吲哚-2-碳酸乙酯; 通过使用氧化铂将其还原，得到（2S，3aS，7aS） - 八氢吲哚-2-碳酸乙酯; 使用氢化铝锂还原它; 在咪唑存在下与氯叔丁基二苯基硅烷反应，得到（2S，3aS，7aS）-2-（叔丁基二苯基甲硅烷氧基甲基）八氢二氢吲哚。 （2R，3R）-2,3-二烷基酒石酸通过以下步骤制备：使2-酮碳酸与（2S，3aS，7aS）-2-（叔丁基二苯基甲硅烷氧基甲基）八氢二氢吲哚（I）在二环己基碳二亚胺 （DDC）得到2-酮酰胺（II）; 频烯醇在六甲基磷酰胺（HMP）的存在下偶联2-酮酰胺（II），得到二烷基酒石酸衍生物; 并水解该衍生物制备（2R，3R）-2,3-二烷基酒石酸（III）。

公开(公告)号：KR100302325B1

公开(公告)日：2001-11-22

申请号：KR1019980051031

申请日：1998-11-26

Applicant: 한국과학기술원

Inventor： 김용해 ,  임진수

IPC: C07D405/04

Abstract: 본 발명은 항암제인 독시플루리딘의 새로운 합성방법에 관한 것으로서 보다 상세하게는 2',3'-아세틸-5-플루오로유리딘을 메탄설포닐 클로라이드로 메실화시켜 2',3'-아세틸-5'-메실-5-플루오로유리딘을 합성하고, 여기에 금속아연과 요오드화 나트륨으로 반응시켜 2',3'-아세틸-5'-디옥시-5-플루오로유리딘을 합성하고 이것을 탈보호화시켜서 독시플루리딘을 합성하는 것을 특징으로 하는 독시플루리딘 제조 방법에 관한 것이다.
또한 본 발명인 독시플루리딘을 합성하는데 있어서 저가이면서 독성이 적은 메탄설포닐 클로라이드, 금속아연, 요오드화 나트륨 외에 초음파를 사용함으로써 독시플루리딘의 수율을 높일 수 높다.

公开(公告)号：KR100058122B1

公开(公告)日：1993-01-08

申请号：KR1019900011010

申请日：1990-07-19

Applicant: 한국과학기술원

Inventor： 김용해 ,  이춘호

IPC: C07D473/02 ,  C07D473/40

公开(公告)号：KR1019910011845A

公开(公告)日：1991-07-30

申请号：KR1019890020247

申请日：1989-12-29

Applicant: 한국과학기술원

Inventor： 김용해 ,  이춘호

IPC: C07D405/04

公开(公告)号：KR100039651B1

公开(公告)日：1991-02-07

申请号：KR1019880001077

申请日：1988-02-05

Applicant: 한국과학기술원

Inventor： 김용해 ,  임상철 ,  박영준

IPC: C07D489/02

公开(公告)号：KR1019900008169B1

公开(公告)日：1990-11-05

申请号：KR1019880013576

申请日：1988-10-18

Applicant: 한국과학기술원

Inventor： 김용해 ,  김중영 ,  이춘호

IPC: C07D239/32

Abstract: Acyclic pyrimidine derivatives of formula (I) are prepared by reacting a cpd. of formula (II) with 2-acetoxyethyl acetoxymethylether or o-chloromethyl-1,3-di-o-benzylglycerol in the presence of cesium iodide and acetonitrile solvent. In the formulas, Z= 2acetoxyethoxymethyl or 1,3-di-o-benzylpropoxymethyl; X= S or O; R1, R2 and R3 each= H, methyl, amine, O or F. (I) have antiviral, anticancer and antibacterial activities.

Abstract translation: 通过使cpd反应制备式（I）的非环嘧啶衍生物。 式（II）的化合物与2-乙酰氧基乙基乙酰氧基甲基醚或邻氯甲基-1,3-二-O-苄基甘油在碘化铯和乙腈溶剂存在下反应。 在式中，Z = 2-乙酰氧基乙氧基甲基或1,3-二邻 - 苄基丙氧基甲基; X = S或O; R1，R2和R3各自为H，甲基，胺，O或F.（I）具有抗病毒，抗癌和抗菌活性。