JPS63112580A - Tetrahydropyrido(2,3-d)pyrimidine derivative - Google Patents
Tetrahydropyrido(2,3-d)pyrimidine derivativeInfo
- Publication number
- JPS63112580A JPS63112580A JP61255858A JP25585886A JPS63112580A JP S63112580 A JPS63112580 A JP S63112580A JP 61255858 A JP61255858 A JP 61255858A JP 25585886 A JP25585886 A JP 25585886A JP S63112580 A JPS63112580 A JP S63112580A
- Authority
- JP
- Japan
- Prior art keywords
- ethyl
- carboxylic acid
- oxopyrido
- pyrimidine
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- VKXUCROJMDAHJO-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine Chemical class C1=CN=C2NCNCC2=C1 VKXUCROJMDAHJO-UHFFFAOYSA-N 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 claims description 3
- -1 6-phenylseleno-8-ethyl-5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid Chemical compound 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 23
- YWWZCHLUQSHMCL-UHFFFAOYSA-N diphenyl diselenide Chemical compound C=1C=CC=CC=1[Se][Se]C1=CC=CC=C1 YWWZCHLUQSHMCL-UHFFFAOYSA-N 0.000 abstract description 10
- JOHZPMXAZQZXHR-UHFFFAOYSA-N pipemidic acid Chemical compound N1=C2N(CC)C=C(C(O)=O)C(=O)C2=CN=C1N1CCNCC1 JOHZPMXAZQZXHR-UHFFFAOYSA-N 0.000 abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract description 3
- 239000012442 inert solvent Substances 0.000 abstract description 3
- 229960001732 pipemidic acid Drugs 0.000 abstract description 2
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 abstract 1
- 239000004599 antimicrobial Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000000034 method Methods 0.000 description 12
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 10
- DWRWSNAREGLUHZ-UHFFFAOYSA-N ethyl pyrimidine-4-carboxylate Chemical compound CCOC(=O)C1=CC=NC=N1 DWRWSNAREGLUHZ-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000005658 halogenation reaction Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- QDISKADULUYVBM-UHFFFAOYSA-N ethyl 3-(diethylamino)propanoate Chemical compound CCOC(=O)CCN(CC)CC QDISKADULUYVBM-UHFFFAOYSA-N 0.000 description 1
- CNRWEHBBGLCEHG-UHFFFAOYSA-N ethyl 3-(ethylamino)propanoate Chemical compound CCNCCC(=O)OCC CNRWEHBBGLCEHG-UHFFFAOYSA-N 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- YPOXGDJGKBXRFP-UHFFFAOYSA-N pyrimidine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC=N1 YPOXGDJGKBXRFP-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003958 selenols Chemical class 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は、抗菌剤として優れた作用を有するピペミド酸
、２−（１−ピペラジニル）−８−エチル−５，８−ジ
ヒドロ−５−オキソピリド（２，３−ｄ〕ピリミジン−
６−カルボン酸に導かれる新規な中間体に関する。Detailed Description of the Invention The present invention provides pipemic acid, 2-(1-piperazinyl)-8-ethyl-5,8-dihydro-5-oxopyride (2,3-d), which has excellent effects as an antibacterial agent. pyrimidine
This invention relates to a novel intermediate derived from 6-carboxylic acid.
従来の技術
ピペミド酸およびその誘導体の製造法については、これ
までに数多くの方法が報告されている。BACKGROUND OF THE INVENTION Many methods for producing pipemide acid and its derivatives have been reported so far.
その中で、式（２）
（式中、Ｒ１はハロゲン原子、チオメチル基、メトキシ
基およびピペラジニル基を、Ｒ２は水素原子または低級
アルキル基を示す）で表される化合物から、式（３）
（式中、Ｒ１およびＲ２は、式（１）におけると同義で
ある）で示される化合物の製法としては、次の方法が知
られている。Among them, compounds represented by formula (2) (wherein R1 represents a halogen atom, thiomethyl group, methoxy group, or piperazinyl group, and R2 represents a hydrogen atom or a lower alkyl group) are selected from compounds represented by formula (3) ( The following method is known as a method for producing the compound represented by the formula (wherein R1 and R2 have the same meanings as in formula (1)).
Ａ法：ハロゲン化を行い対応する６−ハロゲン置換体を
生成せしめ次いで塩基で脱ハロゲン化水素する方法〔特
公昭５５−１６５９４ ＥＢ法；高温下又は、酸化剤等
で直接脱水素する方法〔特公昭５６−５７５３）
しかし、Ａ法においては、ハロゲン化で生成する６−ハ
ロゲン置換体が不安定であり、取扱いが困難であること
および、ハロゲン化の反応において副生成物が避けられ
ないため精製が困難である。Method A: A method of halogenation to produce the corresponding 6-halogen substituted product, followed by dehydrohalogenation with a base [Patent Publication No. 55-16594 EB method; method of direct dehydrogenation at high temperature or with an oxidizing agent, etc. However, in method A, the 6-halogen substituted product produced by halogenation is unstable and difficult to handle, and by-products are unavoidable in the halogenation reaction, so purification is difficult. is difficult.
一方、Ｂ法では、２５０℃以上という高温反応又は、ク
ロラニルや二酸化マンガン等の酸化剤存在下での加熱反
応など、爆発の危険を伴う反応である。などこれら方法
は、工業的製法としては必ずしも満足できるものではな
い。On the other hand, in method B, the reaction involves a risk of explosion, such as a high temperature reaction of 250° C. or higher or a heating reaction in the presence of an oxidizing agent such as chloranil or manganese dioxide. These methods are not necessarily satisfactory as industrial production methods.
発明が解決しようとする問題点
式（３）に示される２−置換−８−エチル−５，８−ジ
ヒドロ−５−オキソピリド［２，３−ｄ）ピリミジン−
６−カルボン酸およびその透導体が安全にかつ収率よく
製造される方法が求められている。Problems to be Solved by the Invention 2-Substituted-8-ethyl-5,8-dihydro-5-oxopyrido[2,3-d)pyrimidine-
There is a need for a method for producing 6-carboxylic acid and its transparent conductor safely and with good yield.
問題点を解決するだめの手段
本発明は、式〔１）
（式中、Ｒ２はハロゲン原子、チオメチル基、メトキシ
基およびピペラジニル基を、Ｒ２は水素原子または、低
級アルキル基を示す）で表される６−フェニルモレツー
８−エチル−５，６，７，８−テトラヒドロ−５−オキ
ソピリド［２，３−ｄ）ピリミジン−６−カルボン酸お
よびその誘導体〔以下、化合物（１）という。他の式番
号の化合物についても同様〕に関する。Means for Solving the Problems The present invention provides a compound represented by the formula [1] (wherein R2 represents a halogen atom, a thiomethyl group, a methoxy group, or a piperazinyl group, and R2 represents a hydrogen atom or a lower alkyl group). 6-phenylmore-8-ethyl-5,6,7,8-tetrahydro-5-oxopyrido[2,3-d)pyrimidine-6-carboxylic acid and its derivatives [hereinafter referred to as compound (1)]. The same applies to compounds with other formula numbers.
化合物（１）のＲ，の定義において、ハロゲン原子は塩
素、臭素を意味する。又、Ｒ２の定義において、低級ア
ルキル基は、炭素数１〜６の直鎮状もしくは分枝状のア
ルキル、例えばメチノベエチノベｎ−プロピノベイソブ
ロピル、ｎ−ブチル、イソブチル、ｎ−ペンチル、イソ
ペンチル等を包含する。In the definition of R in compound (1), the halogen atom means chlorine or bromine. In addition, in the definition of R2, the lower alkyl group is a straight or branched alkyl group having 1 to 6 carbon atoms, such as metinobeethinobe n-propinobeisopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, etc. include.
化合物（１）は、化合物（２）とジフェニルジセレニド
とを不活性溶媒下で反応させることにより得ることがで
きる。Compound (1) can be obtained by reacting compound (2) with diphenyl diselenide in an inert solvent.
たとえば、塩化メチレン等の不活性溶媒中、二酸化セレ
ンおよびジフェニルジセレニドを懸濁させ、次いで少量
の硫酸および化合物（２）を加え、加熱することにより
容易に化合物（１）を得ることができる。For example, compound (1) can be easily obtained by suspending selenium dioxide and diphenyl diselenide in an inert solvent such as methylene chloride, then adding a small amount of sulfuric acid and compound (2), and heating. .
溶媒としては、塩化メチレンの他に、クロロホルム、四
塩化炭素、ジクロルエタン、トリクレンなどが好適に用
いられる。In addition to methylene chloride, chloroform, carbon tetrachloride, dichloroethane, trichlene, and the like are preferably used as the solvent.
二酸化セレンは、ジフェニルジセレニドに対し０．５〜
２．０当量、特に０．８〜１．０当遣用いるのが好まし
い。Selenium dioxide is 0.5 to diphenyl diselenide.
It is preferable to use 2.0 equivalents, particularly 0.8 to 1.0 equivalents.
硫酸は、ジフェニルジセレニドに対し０．２〜１．０当
量、特に０．２〜０．５当量用いるのが好ましい。また
、ジフェニルジセレニドは、化合物（２）に対し１．０
〜１０．０当量、特に１．０〜２．０当量用いるのが好
ましい。Sulfuric acid is preferably used in an amount of 0.2 to 1.0 equivalent, particularly 0.2 to 0.5 equivalent, based on diphenyl diselenide. In addition, diphenyl diselenide has a 1.0
It is preferable to use 1.0 to 2.0 equivalents, particularly 1.0 to 2.0 equivalents.
反応は、室温から溶媒の沸点下で行い、通常１〜１０時
間で終了する。The reaction is carried out at room temperature to below the boiling point of the solvent and is usually completed in 1 to 10 hours.
反応終了液から、化合物（１）の単離、精製は、−般有
機合成で常用される手法が適用される。例えば、反応終
了液を氷水中に産前し、分液を行い、有機層を得る。こ
の有機層を乾燥した後、溶媒を留去することにより化合
物（１）を得ることができる。For isolation and purification of compound (1) from the reaction-completed solution, methods commonly used in general organic synthesis are applied. For example, the reaction-completed solution is placed in ice water and separated to obtain an organic layer. After drying this organic layer, compound (1) can be obtained by distilling off the solvent.
出発化合物である化合物（２）は公知化合物であり、特
開昭５２−１１１５９５に記載の下記に示す方法で合成
することができる（参考例１）。Compound (2), which is a starting compound, is a known compound and can be synthesized by the method described below in JP-A-52-111595 (Reference Example 1).
に、 Ｉ
Ｃ２Ｈ５
（式中、Ｒ１およびＲ２は、式（１）におけると同義で
ある）。, I C2H5 (wherein R1 and R2 have the same meanings as in formula (1)).
すなわち、容易に入手できる２−置換−４−クロロピリ
ミジン−５−カルボン酸エステルと、β−Ｎ−エチルア
ミノプロピオン酸エステルを縮合させて得られる２−置
換−４−（Ｎ−β−カルボエトキシエチル−Ｎ−エチル
）アミノピリミジン−５−カルボン酸エステルをｔ−ブ
トキシカリの様な強塩基を用い、シークマン縮合反応を
行い目的とする化合物〔２〕を容易に合成することがで
きる。That is, 2-substituted-4-(N-β-carboethoxy The desired compound [2] can be easily synthesized by subjecting ethyl-N-ethyl)aminopyrimidine-5-carboxylic acid ester to a Seekman condensation reaction using a strong base such as t-butoxypotassium.
化合物（１）は、室温下での過酸の処理のような穏和な
反応条件で容易に化合物（３）に導くことができる（参
考例２，３）。すなわち化合物（１〕を反応に不活性な
溶媒、例えば、テトラヒドロフランに溶解し、過酸化水
素（３５％）を化合物（１）の５〜１０倍モル加えて反
応する。反応後、溶媒を留去したのち、エチルエーテノ
ペベンゼン、クロロホルム、酢酸エチルなどの有機溶媒
で抽出する。得られた有機層を乾燥後、溶媒を留去すれ
ば化合物（３）が白色結晶として得られる。Compound (1) can be easily led to compound (3) under mild reaction conditions such as treatment with peracid at room temperature (Reference Examples 2 and 3). That is, compound (1) is dissolved in a solvent inert to the reaction, such as tetrahydrofuran, and hydrogen peroxide (35%) is added 5 to 10 times the mole of compound (1) and reacted. After the reaction, the solvent is distilled off. After that, it is extracted with an organic solvent such as ethyl etherenopebenzene, chloroform, ethyl acetate, etc. After drying the obtained organic layer, the solvent is distilled off to obtain compound (3) as white crystals.
実施例 次に本発明の実施例、参考例を示す。Example Next, examples and reference examples of the present invention will be shown.
実施例１
２−クロロ−８−エチル−５，５，７，８−テトラヒド
ロ−５−オキソピリドＣ２，３−ｄ’Ｊ ピリミジン−
６−カルボン酸エチルエステル４．２６ ｇを、二酸化
セレン０．９９ｇ、ジフェニルジセレニド２．８２ｇ、
塩化メチレン１５ｍｊ！および濃硫酸０．１８ ｇを加
えた懸濁液へ加えた。この溶液を、５℃で１時間攪拌し
たのち、２０〜２５℃で１時間さらに還流下で２時間攪
拌する。反応後、反応液を氷水５０＋＋Ｈ！中へ産前し
た後、エチルエーテル５０ｍβで２回抽出する。有機層
は、水洗し、無水硫酸マグネシウムで乾燥したのち減圧
１ＥＨ１１し２４．６３ ｇの褐色油状物を得た。これ
をシリカゲルクロマトグラフィー（西ドイツ、メルク社
製シリカゲルＧ。Example 1 2-chloro-8-ethyl-5,5,7,8-tetrahydro-5-oxopyrido C2,3-d'J pyrimidine-
4.26 g of 6-carboxylic acid ethyl ester, 0.99 g of selenium dioxide, 2.82 g of diphenyl diselenide,
15mj of methylene chloride! and 0.18 g of concentrated sulfuric acid was added to the suspension. This solution is stirred at 5°C for 1 hour, then at 20-25°C for 1 hour, and further stirred under reflux for 2 hours. After the reaction, the reaction solution was soaked in ice water for 50++H! After delivery, extract twice with 50 mβ of ethyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then vacuumed to 1EH11 to obtain 24.63 g of a brown oil. This was subjected to silica gel chromatography (Silica Gel G manufactured by Merck & Co., West Germany).
Ａｒｔ、 ７７３４．展開溶媒；ｎ−ヘキサン：酢酸エ
チル＝３・１）に付し、２−り四ロー６−フエニルセレ
ツー８−エチル−５，６，７，８−テトラヒドロ−５−
オキソピリド〔２，３−ｄ）ピリミジン−６−カルボン
酸エチルエステルの黄褐色の結晶５．７２ ｇを得た。Art, 7734. Developing solvent: n-hexane:ethyl acetate = 3.1) to give 2-di-4-6-phenylcere-8-ethyl-5,6,7,8-tetrahydro-5-
5.72 g of yellowish brown crystals of oxopyrido[2,3-d)pyrimidine-6-carboxylic acid ethyl ester were obtained.
（収率８６％）
融点：１１２℃
Ｉ Ｒ（ＫＢｒ） ： １７４０．１６７０．１５８
５．１５５０．１３５０．１２３０゜１１７０、１０３
０．９３０．７６０ｃｍ−’１ ）１− Ｎ！、ＩＲ（
ＣＯＣｌ、中）δ（ｐｐｍ） ： １．１２ （ｔ
。(Yield 86%) Melting point: 112°C IR (KBr): 1740.1670.158
5.1550.1350.1230゜1170, 103
0.930.760cm-'1)1-N! ,IR(
COCl, medium) δ (ppm): 1.12 (t
.
３Ｈ）、１．１６ （ｔ、３Ｈ） 、３．５２（ｑ、２
Ｈ）、３．７６ （ｄ、２Ｈ）、４．１２ （ｑ、２Ｈ
） 、７．２４〜７．５８（ｍ、５Ｈ）、８．５４ （
ｓ、 ＩＨ）元素分析（立（％）
実測（直 Ｃ：４９，３６ 、 Ｈ：４．１０． Ｎ
：９．６８Ｃ＋ａＨ＋ｅＯＪ＊ＳｅＣｊ！としての計算
値Ｃ：４９．２７ 、 Ｈ：４．１３． Ｎ ：
９．５８実施例２
２−メトキシ−８−エチル−５，６，７，８−テトラヒ
ドロ−５−オキソピリド［：２．３−ｄ：］］ピリミジ
ンー６−カルボン酸エチルエステル４６６ ｇを、二酸
化セレン１．１２ｇ、ジフェニルジセレニド３．１４ｇ
、塩化メチレン１６ｍｆｌおよび濃硫酸０．２ｇを加え
た懸濁液へ加えたのち、実施例１と同様に反応、後処理
を行い、２−メトキシ−６−フェニルモレツー８−エチ
ル−５，６，７，８−テトラヒドロ−５−オキソピリド
［２，３−ｄ）ピリミジン−６−カルボン酸エチルエス
テル６、０ ｇ ヲ（Ｕｓ。3H), 1.16 (t, 3H), 3.52 (q, 2
H), 3.76 (d, 2H), 4.12 (q, 2H
), 7.24-7.58 (m, 5H), 8.54 (
s, IH) Elemental analysis (vertical (%) Actual measurement (direct C: 49.36, H: 4.10.N
:9.68C+aH+eOJ*SeCj! Calculated values as C: 49.27, H: 4.13. N:
9.58 Example 2 466 g of 2-methoxy-8-ethyl-5,6,7,8-tetrahydro-5-oxopyrido[:2.3-d:]]pyrimidine-6-carboxylic acid ethyl ester was added to selenium dioxide. 1.12g, diphenyldiselenide 3.14g
was added to a suspension containing 16 mfl of methylene chloride and 0.2 g of concentrated sulfuric acid, and then reacted and post-treated in the same manner as in Example 1 to obtain 2-methoxy-6-phenylmore-8-ethyl-5,6 ,7,8-tetrahydro-5-oxopyrido[2,3-d)pyrimidine-6-carboxylic acid ethyl ester 6,0 g wo (Us.
融点：１３８℃
Ｉ Ｒ（ＫＢｒ） ＋ １７３８．１６６５．１５９
ＣＩ、 １５５５．１３６５．１２３０゜１１００．９
３０，７６０ ｃａｒ’
’ Ｈ−ＮＭＲ（ＣＤＣｊｉ！ ３ 中）δ（ｐｐｍ）
＋ １．１２ （ｔ。Melting point: 138°C I R (KBr) + 1738.1665.159
CI, 1555.1365.1230°1100.9
30,760 car'' H-NMR (in CDCji! 3) δ (ppm)
+ 1.12 (t.
３Ｈ）、１．１８ （ｔ、３Ｈ）、３．４６（ｓ、３Ｈ
） 、３．５２ （ｑ、２）り、４．１２ （ｑ、 ２
Ｈ）、７．２〜７．５（ｍ、５Ｈ）、８．６ （Ｓ、Ｌ
Ｈ）
元素分析値（％）
実測値 Ｃ：５２．４５ 、 Ｈ：４．９５． Ｎ ：
９．５２ＣＩ９８２１０．Ｎ３Ｓｅとして（７） 計ｘ
ｍＣ：５２．５４ 、 Ｈ：４．８７． Ｎ ：９．６
７実施例３
２−（１−ピペラジニル）−８−エチル−５，６゜７．
８−テトラヒドロ−５−オキソピリドＣ２，３−ｄ〕ピ
リミジン−６−カルボン酸エチルエステル２、５８ ｇ
を、二酸化セレン０．５２ ｇ、ジフェニルジセレニド
１．４６ｇ、塩化メチレン８ｍｌおよび濃硫酸０．１ｇ
を加えた懸濁液へ加えたのち、実施例１と同様に反応、
後処理を行い、２−（１−ピペラジニル）−６−フェニ
ルモレツー８−エチル−５，６，７，８−テトラヒドロ
−５−オキソピリド［：２，３−ｄ）ピリミジン−６−
カルボン酸エチルエステル２．０ｇを得た。3H), 1.18 (t, 3H), 3.46 (s, 3H
) , 3.52 (q, 2) ri, 4.12 (q, 2
H), 7.2-7.5 (m, 5H), 8.6 (S, L
H) Elemental analysis value (%) Actual value C: 52.45, H: 4.95. N:
9.52CI98210. As N3Se (7) Total x
mC: 52.54, H: 4.87. N:9.6
7 Example 3 2-(1-piperazinyl)-8-ethyl-5,6°7.
8-tetrahydro-5-oxopyrido C2,3-d]pyrimidine-6-carboxylic acid ethyl ester 2,58 g
, 0.52 g of selenium dioxide, 1.46 g of diphenyl diselenide, 8 ml of methylene chloride, and 0.1 g of concentrated sulfuric acid.
was added to the suspension, and then reacted in the same manner as in Example 1.
After post-treatment, 2-(1-piperazinyl)-6-phenylmore-8-ethyl-5,6,7,8-tetrahydro-5-oxopyrido[:2,3-d)pyrimidine-6-
2.0 g of carboxylic acid ethyl ester was obtained.
融点：１２５〜１２８℃
Ｉ Ｒ（ＫＢｒ） ： ３４５０．１？３０．１６６０
．１５９０．１５５０．１３４５゜１２６５、１２３５
．１００５．７９０ ｃｚ−’’Ｈ−ＮＭＲ（ＣＤＣｆ
Ｏ中）δ（Ｉｌｐｍ） ： １．１８ （ｔ 。Melting point: 125-128℃ IR (KBr): 3450.1?30.1660
．． 1590.1550.1345゜1265, 1235
．． 1005.790 cz-''H-NMR (CDCf
(in O) δ (Ilpm): 1.18 (t.
３Ｈ）、１．３０ （ｔ、３Ｈ） 、３．１〜３．８
＜ｍ、 １０Ｈ）、４．３０ （ｑ。3H), 1.30 (t, 3H), 3.1-3.8
<m, 10H), 4.30 (q.
２Ｈ）、７．２〜７．６ （ｍ、５Ｈ）、８．６４
（ｓ、ＬＨ）
元素分析値（％）
実測値 Ｃ：５４．０８ 、 Ｈ：５．５５． Ｎ ：
１４．３８Ｃｘ２Ｈ２ｑ０３％＝、Ｓｅとしての計算値
Ｃ：５４．１０ 、 Ｈ：５．５７． Ｎ ：１４．３
４実施例４
２−クロロ−８−エチル−５，６，７，８−テトラヒド
ロ−５−オキソピリド（２，３−ｄｌ ピリミジン−６
−カルボン酸２．２０ ｇを、二酸化セレン０．５０ｇ
１ジフェニルジセレニド１．４２ｇ、塩化メチレン８ｍ
ｆｆ１および濃硫酸０．１ｇを加えた懸濁液へ加えたの
ち、実施例１と同様に反応、後処理を行い、２−１０ロ
ー６−フニニルセレノー８−エチル−５、６，７，８−
テトラヒドロ−５−オキソピリド〔２゜３−ｄ〕ピリミ
ジン−６−カルボン酸１．０ｇを得融点＋ １３６．８
℃
Ｉ Ｒ（ＫＢｒ） ： １７３５．１６６５．１５７
５．１３６０．１２６０．１１２０゜１０１０、９２０
．７５０ ｃｍ−’
’ Ｈ−Ｎ！、ＩＲ（ＣＤＣβ３ 中）δ（＋）Ｉｌｍ
） ＋１．１４ （ｔ。2H), 7.2-7.6 (m, 5H), 8.64
(s, LH) Elemental analysis value (%) Actual value C: 54.08, H: 5.55. N:
14.38Cx2H2q03%=, Calculated value as Se C: 54.10, H: 5.57. N: 14.3
4 Example 4 2-chloro-8-ethyl-5,6,7,8-tetrahydro-5-oxopyride (2,3-dl pyrimidine-6
-2.20 g of carboxylic acid, 0.50 g of selenium dioxide
1.42 g of diphenyl diselenide, 8 m of methylene chloride
After adding it to a suspension containing ff1 and 0.1 g of concentrated sulfuric acid, the reaction and post-treatment were carried out in the same manner as in Example 1 to obtain 2-10 rho 6-funinyl selenol 8-ethyl-5,6,7,8-
Obtained 1.0 g of tetrahydro-5-oxopyrido[2゜3-d]pyrimidine-6-carboxylic acid, melting point + 136.8
°C I R (KBr): 1735.1665.157
5.1360.1260.1120゜1010, 920
．． 750 cm-'' H-N! , IR (in CDCβ3) δ(+)Ilm
) +1.14 (t.
３）（）、３．１８ （ｓ、 ２Ｈ） 、４．１
５（ｑ、 ２Ｈ）、７．２〜７．８ （ｍ。3) (), 3.18 (s, 2H), 4.1
5 (q, 2H), 7.2-7.8 (m.
５Ｈ）、８．６０ （ｓ、 ＩＨ）、１４．３２（ｓ
、ＩＩ（）
元素分析値（％）
実測値 Ｃ：４６．８０ 、 Ｈ：３．４９． Ｎ ＋
１０．２１％Ｃ１６旧＜０３Ｎ、ＳｅＣ１２としての計
算値Ｃ：４６．７９ 、 Ｈ：３．４４． Ｎ ：１０
．２３参考例１
２．４−ジクロロピリミジン−５−カルボン酸エチルエ
ステル１００ｇをトルエン４００ｍＡに溶かした溶液を
攪拌し、５℃に冷却する。これに、Ｎ−エチル−β−ア
ミノプロピオン酸エチルエステル１４０ｇをトルエン１
５０ｍ１に溶かした溶液を５〜１０℃で約１時間かけて
滴下した。滴下したのち室温下で２時間攪拌した。反応
中、Ｎ−エチル−β−エチルアミノプロピオン酸エチル
エステルの塩酸塩の白色結晶が析出する。反応後、この
結晶を濾過し、ｐ液を減圧下でａ縮し溶媒を留去し、２
−クロロ−４−（Ｎ−β−カルボエトキシエチル−Ｎ−
エチル）アミノピリミジン−５−カルボン酸エチルエス
テル１５０ｇが、淡黄色の粘性油状物として得られる。5H), 8.60 (s, IH), 14.32 (s
, II () Elemental analysis value (%) Actual value C: 46.80, H: 3.49. N+
10.21% C16 old<03N, calculated value as SeC12 C: 46.79, H: 3.44. N:10
．． 23 Reference Example 1 A solution of 100 g of 2.4-dichloropyrimidine-5-carboxylic acid ethyl ester dissolved in 400 mA of toluene is stirred and cooled to 5°C. To this, 140 g of N-ethyl-β-aminopropionic acid ethyl ester was added to 1 portion of toluene.
A solution dissolved in 50ml was added dropwise at 5 to 10°C over about 1 hour. After the dropwise addition, the mixture was stirred at room temperature for 2 hours. During the reaction, white crystals of the hydrochloride of N-ethyl-β-ethylaminopropionic acid ethyl ester are precipitated. After the reaction, the crystals were filtered, the p solution was condensed under reduced pressure, the solvent was distilled off, and 2
-chloro-4-(N-β-carboethoxyethyl-N-
150 g of ethyl)aminopyrimidine-5-carboxylic acid ethyl ester are obtained as a pale yellow viscous oil.
（収率７１．７％）これは精製することなく直接次の工
程に用いることができる。(Yield 71.7%) This can be used directly in the next step without purification.
ｔ−ブタノール７２０ｍβにｔ−ブトキシカリ４０、４
ｇを４０℃で溶解させたのち、１０℃に冷却する。こ
の溶液に、２−クロロ−４−（Ｎ−β−カルボエトキシ
エチル−Ｎ−エチル）アミノピリミジン−５−カルボン
酸エチルエステル８９．７ｇを加え、室温下で２時間攪
拌した。反応中、白色結晶が析出する。反応後、反応液
を氷水５００ｍβ中に注油したのち、６Ｎ−塩酸でｐＨ
３に調整すると黄色結晶が析出した。水冷下で晶析した
のち９゜過し水洗した。減圧下で乾燥すれば、２−クロ
ロ−８−エチル−５，６，７，８−テトラヒドロ−５−
オキソピリド［：２．３−ｃｌ）ピリミジン−６−カル
ボン酸エチルエステル７７．１ ｇが、黄色の粉末性結
晶として得られた（収率７４．５％）。720 mβ of t-butanol and 40,4 t-butoxypotassium
After dissolving g at 40°C, cool to 10°C. To this solution, 89.7 g of 2-chloro-4-(N-β-carboethoxyethyl-N-ethyl)aminopyrimidine-5-carboxylic acid ethyl ester was added and stirred at room temperature for 2 hours. During the reaction, white crystals precipitate. After the reaction, the reaction solution was poured into 500 mβ of ice water, and the pH was adjusted with 6N-hydrochloric acid.
When the temperature was adjusted to 3, yellow crystals were precipitated. After crystallization under water cooling, it was filtered through 9° and washed with water. When dried under reduced pressure, 2-chloro-8-ethyl-5,6,7,8-tetrahydro-5-
77.1 g of oxopyrido [:2.3-cl)pyrimidine-6-carboxylic acid ethyl ester were obtained as yellow powdery crystals (yield 74.5%).
融点：１４８℃
Ｉ Ｒ（ＫＢｒ） ： １６６２．１６３５．１５７
５．１５１５．１３７５．１３５７゜１２６０、１０９
０．１０１０．９２０ ｃ山−１’ＨＮＭＲ（ＣＤＣｊ
！ ３ 中）δ（１）Ｉ）ｍ） ： １．１６
（ｔ。Melting point: 148°C IR (KBr): 1662.1635.157
5.1515.1375.1357゜1260, 109
0.1010.920 c mountain-1'HNMR (CDCj
! 3 Medium) δ(1)I)m): 1.16
(t.
３Ｈ）、１．２８ （ｔ、 ３Ｈ） 、３．５０（ｑ
、２Ｈ）、３．７０ （ｍ、ＩＨ）、４．０６〜４．３
６ （ｍ、 ４Ｈ）、８．１４（Ｓ、ＬＨ）
元素分析値（％）
実測値 ｃ ：５０．８２ 、 Ｈ：５．１０． Ｎ
：１４．７５Ｃ＋Ｊ＋＜０ＪｓＣｊ！としての計算値Ｃ
＋５０．７９ 、 Ｈ：５．０７． Ｎ ：１４．８１
参考例２
２−クロロ−６−フェニルモレツー８−エチル−５，６
，７，８−テトラヒドロ−５−オキソピリド〔２，３−
ｄ）ピリミジン−６−カルボン酸エチルエステル４．４
ｇをテトラヒドロフラン１００ｍｆｌに溶解し、室温下
で３５％過酸化水素水１．７ｇを１時間かけてゆっくり
滴下する。滴下したのち、室温下で３時間攪拌する。反
応後、減圧下で溶媒を留去し、得られた油状の残渣に水
１０ｍ１を加えるとすみやかに白色結晶が析出する。晶
析したのちが過し、得られたが液をＩＮ−水酸化す）
ＵラムでｐＨ１０に調整したのち、クロロホルム２０ｍ
１で２回抽出する。有機層を水洗し乾燥後、溶媒を留去
し、淡黄色の粉末性結晶として２−クロロ−８−エチル
−５，８−ジヒドロ−５−オキソピリド［：２．３−ｄ
）ピリミジン−６−カルボン酸エチルエステル１．０ｇ
を得た。3H), 1.28 (t, 3H), 3.50 (q
, 2H), 3.70 (m, IH), 4.06-4.3
6 (m, 4H), 8.14 (S, LH) Elemental analysis value (%) Actual value c: 50.82, H: 5.10. N
:14.75C+J+<0JsCj! The calculated value C as
+50.79, H:5.07. N: 14.81
Reference example 2 2-chloro-6-phenylmore2-8-ethyl-5,6
,7,8-tetrahydro-5-oxopyrido [2,3-
d) Pyrimidine-6-carboxylic acid ethyl ester 4.4
g was dissolved in 100 mfl of tetrahydrofuran, and 1.7 g of 35% hydrogen peroxide solution was slowly added dropwise at room temperature over 1 hour. After the dropwise addition, the mixture was stirred at room temperature for 3 hours. After the reaction, the solvent is distilled off under reduced pressure, and 10 ml of water is added to the resulting oily residue to immediately precipitate white crystals. After crystallization, the obtained liquid was IN-hydroxylated)
After adjusting the pH to 10 with U ram, add 20 m of chloroform.
Extract twice with 1. After washing the organic layer with water and drying, the solvent was distilled off to obtain 2-chloro-8-ethyl-5,8-dihydro-5-oxopyride [:2.3-d] as pale yellow powdery crystals.
) Pyrimidine-6-carboxylic acid ethyl ester 1.0g
I got it.
参考例３
２− （１−ピペラジニル１６−フェニルモレツー８−
エチル−５，６，７，８−テトラヒドロ−５−オキソピ
リド〔２，３−ｄ）ピリミジン−６−カルボン酸エチル
エステル３．０ｇをテトラヒドロフラン１２０Ｔｎｊ２
に溶解し、室温下で３５％過酸化水素２．０ｇを加え、
参考例２と同様に反応、後処理ヲ行い、２− （１−ピ
ペラジニル）−８−エチル−５，８−ジヒドロ−５−オ
キソピリド［２，３−ｄ）ピリミジン−６−カルボン酸
エチルエステル０．８ｇを得た。Reference example 3 2-(1-piperazinyl 16-phenylmore2-
3.0 g of ethyl-5,6,7,8-tetrahydro-5-oxopyrido [2,3-d) pyrimidine-6-carboxylic acid ethyl ester was added to 120 Tnj2 of tetrahydrofuran.
and add 2.0 g of 35% hydrogen peroxide at room temperature.
The reaction and post-treatment were carried out in the same manner as in Reference Example 2, and 2-(1-piperazinyl)-8-ethyl-5,8-dihydro-5-oxopyrido[2,3-d)pyrimidine-6-carboxylic acid ethyl ester 0 .8g was obtained.
この２− （１−ピペラジニル）−８−エチル−５，８
−ジヒドロ−５−オキソピリド［：２．３−ＣＤピリミ
ジン−６−カルボン酸エチルエステル０．５５ｇをエタ
ノールｌＱｍ、ｉ！および、２Ｎ−水酸化ナトリウム５
ｍｌの混液中で３時間攪拌した。反応後、５℃に冷却し
たのち、酢酸でｐＨ６，５に調整した。この時白色結晶
が析出する。水冷下で晶析したのち７濾過、水洗後、乾
燥すると、微黄色の粉末結晶として２−（１−ピペラジ
ニル）−３−エチル−５，８−ジヒドロ−５−オキソピ
リド〔２，３−ｄ〕 ピリミジン−６−カルボン酸くピ
ペミド酸）０．５ｇを得た。This 2-(1-piperazinyl)-8-ethyl-5,8
-dihydro-5-oxopyride [: 0.55 g of 2.3-CD pyrimidine-6-carboxylic acid ethyl ester in ethanol lQm, i! and 2N-sodium hydroxide 5
ml of the mixed solution for 3 hours. After the reaction, the mixture was cooled to 5°C and adjusted to pH 6.5 with acetic acid. At this time, white crystals precipitate. After crystallization under water cooling, filtration, washing with water, and drying yields 2-(1-piperazinyl)-3-ethyl-5,8-dihydro-5-oxopyride [2,3-d] as a pale yellow powder crystal. 0.5 g of pyrimidine-6-carboxylic acid (pipemidic acid) was obtained.
Claims (1)
シ基およびピペラジニル基を、Ｒ＿２は水素原子または
低級アルキル基を示す）で表される６−フェニルセレノ
−８−エチル−５，６，７，８−テトラヒドロ−５−オ
キソピリド〔２，３−ｄ〕ピリミジン−６−カルボン酸
およびその誘導体。[Claims] Formula (1) ▲Mathematical formulas, chemical formulas, tables, etc.▼(1) (In the formula, R_1 is a halogen atom, thiomethyl group, methoxy group, or piperazinyl group, and R_2 is a hydrogen atom or a lower alkyl group. 6-phenylseleno-8-ethyl-5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid and its derivatives.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61255858A JPS63112580A (en) | 1986-10-29 | 1986-10-29 | Tetrahydropyrido(2,3-d)pyrimidine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61255858A JPS63112580A (en) | 1986-10-29 | 1986-10-29 | Tetrahydropyrido(2,3-d)pyrimidine derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63112580A true JPS63112580A (en) | 1988-05-17 |
Family
ID=17284561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61255858A Pending JPS63112580A (en) | 1986-10-29 | 1986-10-29 | Tetrahydropyrido(2,3-d)pyrimidine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63112580A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6490331A (en) * | 1987-09-30 | 1989-04-06 | Aisin Seiki | Jet nozzle apparatus of human body privates washing machinery |
-
1986
- 1986-10-29 JP JP61255858A patent/JPS63112580A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6490331A (en) * | 1987-09-30 | 1989-04-06 | Aisin Seiki | Jet nozzle apparatus of human body privates washing machinery |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69723846T2 (en) | Process for the preparation of sildenafil | |
| EP0274379B1 (en) | Process for preparing pyridine-2,3-dicarboxylic acid compounds | |
| EP1669359B1 (en) | A process for the preparation of olanzapine and an intermediate therefor | |
| US4634768A (en) | Halo-containing 3-methylflavone-8-carboxylic acid derivatives | |
| JP4408578B2 (en) | 3- (1-Hydroxy-pentylidene) -5-nitro-3H-benzofuran-2-one, production method thereof and use thereof | |
| WO1998005657A1 (en) | 2,3-dihydro-1,4-benzothiazepines, their preparation and their use as intermediates | |
| NZ202981A (en) | A process for the preparation of pyrazino(2,1-a)isoquinoline derivatives | |
| JPS63112580A (en) | Tetrahydropyrido(2,3-d)pyrimidine derivative | |
| JP2524491B2 (en) | Novel aminocarboxylic acid ester and process for producing the same | |
| EP0388620B1 (en) | Process for the preparation of o-carboxypyridyl- and o-carboxyquinolylimidazolinones | |
| NO147838B (en) | INTERMEDIATE FOR USE IN PREPARATION OF THE HYPOTENSIVE AGENT 2- (4- (2-FUROYL) PIPERAZIN-1-YL) -4-AMINO-6,7-DIMETOXYKINAZOLINE | |
| KR100302346B1 (en) | A method of preparing 6-hydroxy-2-oxo-1,2,3,4-tetrahydroquinoline | |
| CZ294957B6 (en) | Process for preparing a substituted imidazopyridine compound | |
| US4927970A (en) | Substituted 3-cyclobutene-1,2-dione intermediates | |
| EP0751945B1 (en) | PROCESS FOR PREPARING (1H-TETRAZOL-5-yl)TETRAZOLO 1,5-a] QUINOLINES AND NAPHTHYRIDINES | |
| JPH04169583A (en) | Phenothiazine derivative and its production | |
| KR910003630B1 (en) | Benzoyl acetic ester derivatives and there of method | |
| JPH05140157A (en) | Phenothiazine derivative | |
| JP3534816B2 (en) | Method for producing methylthiobenzenes | |
| US4235813A (en) | Aromatic sulfonamide sulfonyl chloride compounds | |
| JP2561500B2 (en) | Process for producing pyridine-2,3-dicarboxylic acid derivative | |
| HU193454B (en) | Process for producing 3-phenyl-butyraldehyde derivatives | |
| KR860000671B1 (en) | Process for preparing piperazinyl derivatives of quinoline carboxylic acid | |
| EP0031120B1 (en) | A process for the production of 2-substituted 6-alkoxycarbonyl-8-ethyl-5-oxo-5,8-dihydro-pyrido(2,3-d)-pyrimidines and of corresponding free acids | |
| JPH05320107A (en) | 3-dialkylamino-2-substituted benzoylacrylic acid derivative |