JPH03148281A - Triazolopyrazinone derivative and its preparation - Google Patents
Triazolopyrazinone derivative and its preparationInfo
- Publication number
- JPH03148281A JPH03148281A JP2108995A JP10899590A JPH03148281A JP H03148281 A JPH03148281 A JP H03148281A JP 2108995 A JP2108995 A JP 2108995A JP 10899590 A JP10899590 A JP 10899590A JP H03148281 A JPH03148281 A JP H03148281A
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- carbon atoms
- tables
- formulas
- triazolopyrazinone
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000002253 acid Substances 0.000 claims abstract description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- YJCWLHAPRBRUDO-UHFFFAOYSA-N 2-(2-carbamothioylhydrazinyl)-2-oxoacetamide Chemical compound C(C(=O)N)(=O)NNC(=S)N YJCWLHAPRBRUDO-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 8
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims 2
- 150000003141 primary amines Chemical class 0.000 claims 2
- 230000002378 acidificating effect Effects 0.000 claims 1
- 150000003973 alkyl amines Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 23
- 238000000034 method Methods 0.000 abstract description 6
- 239000000543 intermediate Substances 0.000 abstract description 5
- 229930186147 Cephalosporin Natural products 0.000 abstract description 3
- 229940124587 cephalosporin Drugs 0.000 abstract description 3
- 150000001780 cephalosporins Chemical class 0.000 abstract description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 1
- BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical compound C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 abstract 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- 239000003899 bactericide agent Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 26
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 18
- 238000000921 elemental analysis Methods 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 239000013078 crystal Substances 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- -1 cyclohebutyl Chemical group 0.000 description 5
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical group C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- MLCNOCRGSBCAGH-UHFFFAOYSA-N 2,3-dichloropyrazine Chemical compound ClC1=NC=CN=C1Cl MLCNOCRGSBCAGH-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical compound NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 102220133487 rs149819112 Human genes 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は、新規なトリアゾロピラジノン誘導体及びその
製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a novel triazolopyrazinone derivative and a method for producing the same.
（従来の技術）
Ｊ、Ｈｅｔｅｒｏｃｙｃｌｉｃ ｃｈｅｍ、、 （Ｉ
９８６） ２３゜１１３には、下記一般式（ＩＩ）のト
リアゾロピラジノン誘導体の製造方法が紹介されており
、この化合物は一般式（ＩＩＩ ）のジクロロビラジノ
ンにヒドラジンを反応させて一般式（ＩＶ）のヒドラジ
ノビラジノンを製造した後、これを塩基の存在下で二硫
化炭素と反応させて環化して製造している。(Prior art) J, Heterocyclic chem, (I
986) 23゜113 introduces a method for producing a triazolopyrazinone derivative of the following general formula (II), and this compound is prepared by reacting dichlorovirazinone of the general formula (III) with hydrazine to obtain the general formula ( After producing hydrazinovirazinone (IV), this is reacted with carbon disulfide in the presence of a base to cyclize it.
（ＩＩ） （ｍ） （ｒＶ
）発明者等はセファロスポリン誘導体の有用な中間体と
して使用することのできる後記一般式（Ｉ）のトリアゾ
ロピラジノン誘導体を製造するために、上記に公知の製
造技術を利用して試みた。すなわち、下記一般式（Ｖ）
のクロロビラジノンを製造し、次いで一般式（Ｖｌ）の
ヒドラジノを経て、かつ大部分の反応条件は水の無い状
態で行なわなければならなかった。特に一般式（Ｖ）の
クロロビラジノンは分離するのが難しかった。(II) (m) (rV
) The inventors attempted to produce a triazolopyrazinone derivative of general formula (I) described below, which can be used as a useful intermediate for cephalosporin derivatives, using the above-mentioned known production technology. . That is, the following general formula (V)
of the chlorovirazinone, then via the hydrazino of the general formula (Vl), and most of the reaction conditions had to be carried out in the absence of water. In particular, chlorovirazinone of general formula (V) was difficult to separate.
それだけでなく、一般式（Ｖ）において、Ｒが水素原子
である場合にはＪ、 Ｏｒｇ、 Ｃｈｅｍ、。In addition, in general formula (V), when R is a hydrogen atom, J, Org, Chem.
（Ｉ９７２）３７．２２１に記載のように一般式（Ｖｌ
ｌ）のジクロロピラジンが生成した。(I972) 37.221, the general formula (Vl
1) dichloropyrazine was produced.
（Ｖ） （Ｖｌ）
（■）（発明が解決しようとする課題）
上記のように、一般式（Ｉ）のトリアゾロピラジノン誘
導体を公知の方法で製造するには多くの問題点があるの
で、鋭意研究の結果、新しい製造方法を見いだした。(V) (Vl)
(■) (Problems to be Solved by the Invention) As mentioned above, there are many problems in producing the triazolopyrazinone derivative of general formula (I) by known methods, and as a result of intensive research, Found a new manufacturing method.
（課題を解決するための手段）
−Ｍ式（■）の才キサリルチオセミ力ルバジド°数式（
ＩＸ）のオキサモイルチオセミカルバジドとし、これに
塩基を反応させて一般式（Ｘ）のトリアゾリン誘導体と
し、これを酸で処理して一般式（Ｉ）のトリアゾロピラ
ジノン誘導体を製造することができる。(Means for solving the problem) −M formula (■) of xalylthiosemicorbazide °mathematical formula (
Oxamoylthiosemicarbazide of IX) is reacted with a base to obtain a triazoline derivative of general formula (X), and this can be treated with an acid to produce a triazolopyrazinone derivative of general formula (I). .
（■）
（ＩＸ）
（Ｘ）
（Ｉ）
上記式（Ｉ）、（■）、（ＩＸ）及び（Ｘ）において、
Ｒは水素、炭素数１〜６個のアルキル基、例えばメチル
、エチル、プロピル、ブチル、ペンチル、ヘキシル基、
または炭素数３〜６個のシクロアルキル基、例えばシク
ロプロピル、シクロブチル、シクロへブチル、シクロヘ
キシル基、またはフリル基を表わし、Ｒ′は炭素数１〜
４個の低級アルコキシ基、例えばメトキシ、エトキシ、
プロポキシ基を表わす。(■) (IX) (X) (I) In the above formulas (I), (■), (IX) and (X),
R is hydrogen, an alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl group,
or a cycloalkyl group having 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclohebutyl, cyclohexyl, or furyl group, and R' is a cycloalkyl group having 1 to 6 carbon atoms;
4 lower alkoxy groups, such as methoxy, ethoxy,
Represents a propoxy group.
本発明の製造方法をより詳細に説明すれば、前記一般式
（■）で表わされるオキサリルチオセミカルバジドに、
１．５〜３当量のアンモニア水又は−級アミンを１５〜
３０°Ｃで水又は水とアルコールの混合溶媒中で１〜３
時間反応させて前記一般式（ＩＸ）のオキサモイルチオ
セミカルバジドとし、これに８０〜ｌｏＯ’ｃで１〜２
当量の塩基性溶液を１時間環化反応させて前記の一般式
（Ｘ）の新規なトリアゾリン誘導体とし、これを１〜１
．５当量の５〜ｌＯ％酸性溶液で１時間還流して処理し
１分子内線合させることで目的の前記一般式（Ｉ）のト
リアゾロピラジノン誘導体を製造するものである。To explain the production method of the present invention in more detail, oxalylthiosemicarbazide represented by the general formula (■),
1.5 to 3 equivalents of ammonia water or -class amine to 15 to 3 equivalents
1 to 3 in water or a mixed solvent of water and alcohol at 30°C.
The oxamoyl thiosemicarbazide of the general formula (IX) is obtained by reacting for 1 to 2 hours at 80 to loO'c.
An equivalent amount of the basic solution is subjected to a cyclization reaction for 1 hour to obtain a novel triazoline derivative of the general formula (X), which is
．． The desired triazolopyrazinone derivative of general formula (I) is produced by refluxing for 1 hour with 5 equivalents of a 5-10% acidic solution and performing intramolecular line combination.
一般式（Ｘ）の化合物の製造時に使用することのできる
塩基としては、例えば炭酸水素ナトリウム、炭酸水素カ
リウム、炭酸ナトリウム、炭酸カリウム、水酸化ナトリ
ウム、及び水酸化カリウムの中から選択される水溶液が
好適に用いられる。Examples of bases that can be used in the production of the compound of general formula (X) include aqueous solutions selected from sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide. Suitably used.
分子内縮合反応時に使用することのできる酸としては、
例えば塩酸、硫酸、硝酸の中から選択される水溶液が好
適に用いられる。Acids that can be used during intramolecular condensation reactions include:
For example, an aqueous solution selected from hydrochloric acid, sulfuric acid, and nitric acid is preferably used.
本発明の方法を実施するに際して一般式（■）の化合物
を出発物質として、水溶媒中で一般式（ＩＸ）の化合物
と一般式（Ｘ）の中間体化合物等を分離する工程を省い
て連続的な反応によって、反応液中に結晶として析出す
る目的の一般式（Ｉ）の化合物を得、単にこれを濾過す
ることにより純粋でかつ高い収率（６４〜６８％）で一
般式（Ｉ）の化合物を製造することもできる。勿論、使
用目的によっては、一般式（ＩＸ）及び一般式（Ｘ）で
表わされる中間体を各々分離してち製造することができ
る。When carrying out the method of the present invention, the compound of the general formula (■) is used as a starting material, and the process of separating the compound of the general formula (IX) and the intermediate compound of the general formula (X), etc. in an aqueous solvent is omitted, and the method is continuously carried out. By this reaction, the desired compound of general formula (I) is obtained which precipitates as crystals in the reaction solution, and by simply filtering it, general formula (I) is obtained in a pure and high yield (64-68%). It is also possible to produce compounds of Of course, depending on the purpose of use, the intermediates represented by general formula (IX) and general formula (X) can be separated and then produced.
（発明の効果）
上記のように、本発明の方法によれば、容易に得ること
のできる公知の基礎原料物質である一般式（■）のオキ
サリルチオセミカルバジドから一般式（ＩＸ）のオキサ
モイルチオカルバジドを製造し、これをＧｅｒ、 ０ｆ
ｆｅｎ、 ｌ ９４３９１５及び２７３５１５Ｂに知ら
れている環化反応を利用して、新規化合物である一般式
（Ｘ）のトリアゾリン誘導体を合成し、これを分子内縮
合反応させることによって、高い収率で一般式（Ｉ）の
新規化合物トリアゾロピラジノン誘導体を製造すること
ができる。一般式（Ｉ）のトリアゾロピラジノン誘導体
は、殺菌剤として有用であり、またセファロスポリン誘
導体等の合成中間体としても利用できる。(Effects of the Invention) As described above, according to the method of the present invention, oxamoylthiosemicarbazide of general formula (IX) can be obtained from oxalylthiosemicarbazide of general formula (■), which is a known basic raw material that can be easily obtained. Produce carbazide and convert it into Ger, 0f
By using the cyclization reaction known in fen, l 943915 and 273515B, a new triazoline derivative of general formula (X) is synthesized, and by intramolecular condensation reaction, the general Novel compound triazolopyrazinone derivatives of formula (I) can be prepared. The triazolopyrazinone derivative of general formula (I) is useful as a fungicide and can also be used as a synthetic intermediate for cephalosporin derivatives and the like.
（実施例）
本発明の実施例を挙げ、より具体的に説明すれば次の通
りである。しかし、これら実施例は本発明を限定するも
のではなく、本発明の請求の範囲内で当業者による修正
及び変更は可能である。(Example) Examples of the present invention will be described in more detail as follows. However, these examples do not limit the present invention, and modifications and changes can be made by those skilled in the art within the scope of the claims of the present invention.
実施例１
４− （２，２−ジメトキシエチル）−１−エチルオキ
サリル−３−チオセミカルバジド（■）２７．９ｇ （
０，１モル）を水２００ｍｔ＋に溶かした後、２８％ア
ンモニア水４２１１１１（０，３モル）を加え、１５〜
３０℃で２時間撹拌反応させた後、減圧下で過剰のアン
モニアと水を除去した。Example 1 27.9 g of 4-(2,2-dimethoxyethyl)-1-ethyloxalyl-3-thiosemicarbazide (■) (
After dissolving 0.1 mol) in 200 mt+ of water, add 28% ammonia water 421111 (0.3 mol),
After stirring and reacting at 30° C. for 2 hours, excess ammonia and water were removed under reduced pressure.
反応残留物にエタノール２００−を加えて溶かした後、
減圧下で再び溶媒を除去し、残留物にエチルエーテル２
００−を加えて結晶化し、濾過してエタノールで再結晶
し、純粋な目的化合物である白色の固体２０．０ｇ （
８０％収率）を得た。After adding 200% of ethanol to the reaction residue and dissolving it,
The solvent was removed again under reduced pressure and the residue was diluted with ethyl ether 2
00- was added to crystallize, filter, and recrystallize with ethanol to obtain 20.0 g of a white solid, which is the pure target compound (
80% yield) was obtained.
融点：１７２−１７３℃
’Ｈ−ＮＭＲδ （ＤＭＳＯ−ｄ’）： ３．２９（ｓ
、６）１．０ＣＨｓ）、３．４９ （ｔ。Melting point: 172-173°C 'H-NMRδ (DMSO-d'): 3.29 (s
, 6) 1.0CHs), 3.49 (t.
２Ｈ，ＣＨｓ ） 、４．５６ （ｔ、ＬＨ。2H, CHs), 4.56 (t, LH.
ＣＨ）、 ８． ０１ （ｍ、 ３Ｈ，ＮＨ＋Ｎ
Ｈ２） ９． ９２ （ｂｓ、 ２Ｈ。CH), 8. 01 (m, 3H, NH+N
H2) 9. 92 (BS, 2H.
ＮＨＮＨ）。NHNH).
元素分析（Ｃ，Ｈ，４Ｎ４０４Ｓ）
理論値： Ｃ３３，５９Ｈ５，６４Ｎ２２．３９％実測
値： Ｃ３３，６３Ｈ５，２９Ｎ２２．３０％実施例２
４− （２，２−ジメトキシエチル）−１−エチルオキ
サリル−３−チオセミカルバジド（■）２７．９ｇ （
０，１モル）を水２００１ｎ１に溶かした後、４０％メ
チルアミン水溶液２６ｍｌ１（０，３モル）を加え、１
５〜２０℃で２時間撹拌反応させた後、減圧下で過剰の
アンモニアと水を除去した。反応残留物にエタノール２
００−を加えて溶かした後、減圧下で再び溶媒を除去し
、残留物にエチルエーテル２００１！ｄ！を加えて結晶
化し、濾過してエタノールで再結晶して、純粋な目的化
合物である白色の固体２１．９ｇ （８３％収率）を得
た。Elemental analysis (C, H, 4N404S) Theoretical value: C33,59H5,64N22.39% Actual value: C33,63H5,29N22.30% Example 2 4-(2,2-dimethoxyethyl)-1-ethyloxalyl- 3-thiosemicarbazide (■) 27.9g (
After dissolving 0.1 mol) in 2001 n1 of water, 26 ml of 40% methylamine aqueous solution (0.3 mol) was added, and 1
After stirring and reacting at 5 to 20°C for 2 hours, excess ammonia and water were removed under reduced pressure. Add 2 ethanol to the reaction residue
After adding and dissolving 00-, the solvent was removed again under reduced pressure, and ethyl ether 2001! was added to the residue. d! was added to crystallize, filtered and recrystallized with ethanol to obtain 21.9 g (83% yield) of a white solid, which was the pure target compound.
融点：１６７−１６８℃
’Ｈ−ＮＭＲδ （ＤＭＳＯ−ｄ’ｌ： ２．６６（ｄ
、３Ｈ，ＣＨ，） 、３．２９ （ｓ。Melting point: 167-168°C 'H-NMRδ (DMSO-d'l: 2.66(d
,3H,CH,) ,3.29 (s.
６Ｈ，ＱＣ）Ｉｍ）、３．５０ （ｔ、２Ｈ。6H, QC) Im), 3.50 (t, 2H.
ＣＨｓ）、４．５６ （ｔ、ＩＨ，ＣＨ）。CHs), 4.56 (t, IH, CH).
８．００ （ｂｔ、ＩＨ，ＮＨ）、８．７３（ｂｑ、Ｉ
Ｈ，Ｃ０Ｎ）ＩＣ）、９．８２（ｂｓ、２Ｈ，Ｎ）ＩＮ
Ｈ）。8.00 (bt, IH, NH), 8.73 (bq, I
H, C0N) IC), 9.82 (bs, 2H, N) IN
H).
元素分析（Ｃ，Ｈ，、Ｎ、Ｏ，Ｓ）
理論値： Ｃ３３，３６Ｈ６，１０Ｎ２１．２０％実測
値： Ｃ３６，２３Ｈ６，２０Ｎ２１．１８％実施例３
４− （２，２−ジメトキシエチル）−１−エチルオキ
サリル）−３−チオセミカルバジド（■）２７．９ｇ
（０，１モル）を水２００−に溶かした後、７０％エチ
ルアミン水溶液２４ｄＣ０，３モル）を加え、１５〜２
０”Ｃで２時間撹拌反応させた後、減圧下で過剰のエチ
ルアミンと水を除去した０反応残留物にエタノール２０
０ｍ１’を加えて溶かした後、減圧下で更に溶媒を除去
し、残留物にエチルエーテル２００１ｄを加えて結晶化
し、？濾過してエタノールで再結晶して、純粋な目的化
合物である白色の固体２３．１ｇ （８３％収率）を得
た。Elemental analysis (C, H,, N, O, S) Theoretical value: C33,36H6,10N21.20% Actual value: C36,23H6,20N21.18% Example 3 4- (2,2-dimethoxyethyl)- 27.9 g of 1-ethyloxalyl)-3-thiosemicarbazide (■)
After dissolving (0.1 mol) in 200 - of water, add 24 dC (0.3 mol) of a 70% aqueous solution of ethylamine, and add 15 to 2
After reacting with stirring at 0"C for 2 hours, excess ethylamine and water were removed under reduced pressure, and 20% ethanol was added to the reaction residue.
After adding 0ml' and dissolving it, the solvent was further removed under reduced pressure, and ethyl ether 2001d was added to the residue to crystallize it. After filtration and recrystallization from ethanol, 23.1 g (83% yield) of a white solid, which is the pure target compound, was obtained.
融点：１３６−１３８℃
’Ｈ−ＮＭＲδ （ＤＭＳＯ−ｄ’）： １．０６（ｔ
、３Ｈ，ＣＨｓ ）、３．２３ （ｍ。Melting point: 136-138°C 'H-NMRδ (DMSO-d'): 1.06 (t
, 3H,CHs), 3.23 (m.
２Ｈ，ＮＣＨ＊） 、３．２９ （ｓ、６Ｈ。2H, NCH*), 3.29 (s, 6H.
ＯＣＲ，） ３．４９ （ｔ、２Ｈ。OCR,) 3.49 (t, 2H.
ＣＨ，）、４．５６ （ｔ、ＩＨ，ＣＨ）、８．０３
（ｂＳ、ＩＨ，ＮＨ）、８．７９（ｂｔ、ＬＨ，Ｃ０Ｎ
ＨＣ） 、９．５２（ｂｓ、２Ｈ，ＮＨＮＨ）。CH,), 4.56 (t, IH, CH), 8.03
(bS, IH, NH), 8.79 (bt, LH, C0N
HC), 9.52 (bs, 2H, NHNH).
元素分析（Ｃ，Ｈ，、Ｎ、０４Ｓ）
Ｔ’ＪＡＦａ（ａ：Ｃ３Ｆ１．８４８６．５２Ｎ２１１
．＋３’Ａ実測値： Ｃ３８，８９
実施例４
Ｈ６，６１
Ｎ２０．０８
％
４− （２，２−ジメトキシエチル）−１−エチルオキ
サリル−３−チオセミカルバジド（■）２７．９ｇ （
０，１モル）を水２００−に溶かした後、シクロプロピ
ルアミン１７．１ｇ（０，３モル）を加え、２０〜２５
℃で３時間撹拌反応させた後、減圧下で過剰のシクロプ
ロピルアミンと水を除去した０反応残留物にエタノール
２００ｍｔ’を加えて溶かした後、減圧下で再び溶媒を
除去し、残留物にエチルエーテル２００１ｄ！を加えて
結晶化し、濾過しエタノールで再結晶して、純粋な目的
化合物である白色の固体２５．３ｇ（８７％収率）を得
た。Elemental analysis (C, H,, N, 04S) T'JAFa (a: C3F1.8486.52N211
．． +3'A actual value: C38,89 Example 4 H6,61 N20.08% 4-(2,2-dimethoxyethyl)-1-ethyloxalyl-3-thiosemicarbazide (■) 27.9 g (
After dissolving 0.1 mol) in 200 g of water, 17.1 g (0.3 mol) of cyclopropylamine was added, and 20 to 25
After reacting with stirring at ℃ for 3 hours, excess cyclopropylamine and water were removed under reduced pressure. 200 mt' of ethanol was added to the reaction residue to dissolve it, and the solvent was removed again under reduced pressure. Ethyl ether 2001d! was added to crystallize, filtered and recrystallized with ethanol to obtain 25.3 g (87% yield) of a white solid, which was the pure target compound.
融点：１６２−１６３℃
’Ｈ−ＮＭＲδ （ＤＭＳＯ−ｄ’ｌ： ｏ、６６（ｍ
、４Ｈ，シクロプロピル）
（ｍ、ＩＨ，シクロプロピル）
（ｓ、６Ｈ，（）ＣＨａ） 、３゜
２Ｈ，ＣＨ，）、４．６２
ＣＨ）、８．０６ （ｂｔ。Melting point: 162-163°C 'H-NMRδ (DMSO-d'l: o, 66(m
, 4H, cyclopropyl) (m, IH, cyclopropyl) (s, 6H, () CHa) , 3° 2H, CH,), 4.62 CH), 8.06 (bt.
８．８９ （ｄ、ＩＨ。8.89 (d, IH.
１０．０９ （ｂｓ、２Ｈ。10.09 (BS, 2H.
元素分析（Ｃ，ＯＨ，ａＮ、０４Ｓ） 理論値： Ｃ４１，３７Ｈ６，２５ 実測値： Ｃ４１，４Ｌ Ｈ６，３５実施例５ Ｎ１９．２７ ％ 、 ２． ７６ 、３． ３０ ５３ （ｔ。Elemental analysis (C, OH, aN, 04S) Theoretical value: C41,37H6,25 Actual value: C41,4L H6,35 Example 5 N19.27% , 2. 76 , 3. 30 53 (t.
（ｔ、 ＩＨ。(t, IH.
ＬＨ，ＮＨ） 、 Ｃ０ＮＨＣ） 、 ＮＨＮＨ）。LH, NH), C0NHC), NHNH).
Ｎ１９．３０ ％
２００ｍｔ’の水に４− （２，２−ジメトキシエチル
）−１−才キサモイル−３−チオセミカルバジド２５．
０ｇ （０，１モル）と炭酸水素ナトリウム９．２ｇ
（０，１１モル）を加え、１時間９０±１０℃で反応さ
せた後１反応溶液を冷却し、５％の塩酸水溶液でｐＨ５
に調節した。この時析出する固体を濾過し、炉液はメチ
ルエチルケトン（ＭＥＫ）３００ｍｌ’で抽出し、ＭＥ
Ｋ溶液に濾過した固体を溶かした後、無水芒硝で乾燥し
た後、減圧下で溶媒を除去し、残留物をエタノールで結
晶化し、純粋な目的化合物である白色の固体１７．９ｇ
（７７％収率）を得た。N19.30% 4-(2,2-dimethoxyethyl)-1-year-old xamoyl-3-thiosemicarbazide in 200 mt' of water 25.
0 g (0.1 mol) and 9.2 g of sodium bicarbonate
(0.11 mol) was added and reacted at 90 ± 10°C for 1 hour. The reaction solution was cooled and adjusted to pH 5 with 5% aqueous hydrochloric acid solution.
It was adjusted to The solid precipitated at this time was filtered, and the furnace solution was extracted with 300 ml of methyl ethyl ketone (MEK).
After dissolving the filtered solid in the K solution and drying with anhydrous sodium sulfate, the solvent was removed under reduced pressure and the residue was crystallized with ethanol to obtain 17.9 g of a white solid, which is the pure target compound.
(77% yield).
融点：１９３−１９４℃
ＩＲ（ＫＢｒ）：１６７４．１２８０ｃｍ−’’Ｈ−Ｎ
ＭＲδ（ＤＭＳＯ−ｄ’）： ３．２７（ｓ、６Ｈ，Ｏ
ＣＨ，）、４．４６ （ｄ。Melting point: 193-194℃ IR (KBr): 1674.1280cm-''H-N
MRδ(DMSO-d'): 3.27(s,6H,O
CH,), 4.46 (d.
２Ｈ，ＣＨａ ） 、４．７１ （ｔ、ＩＨ。2H, CHa), 4.71 (t, IH.
ＣＨ） 、７．９７そして８．３１ （ｓ。CH), 7.97 and 8.31 (s.
ＩＨ，ＮＨｘ）、１３．２ （ｂｓ、ＩＨ。IH, NHx), 13.2 (bs, IH.
Ｈ−２）。H-2).
元素分析（Ｃ７０，２Ｎ４０１Ｓ）
理論値： Ｃ３６，２１Ｈ５，２１Ｎ２４．１３％実測
値： Ｃ３６，２８Ｈ５，２３Ｎ２４．２２％実施例６
５− Ｎ−メチルカルバモイル −４−２゜２−ジメ
トキシエチル −１，２，４−）リアゾリン−３−チオ
ンの Ｘ、Ｒ＝メチル、Ｒ′２００−の水に４−
（２，２−ジメトキシエチル）−１−（Ｎ−メチルオキ
サモイル）−３−チオセミカルバジド２６．４ｇ （０
，１モル）と炭酸水素ナトリウム９．２ｇ （０，１１
モル）を加え、１時間９０±１０℃で反応させた後１反
応溶液を冷却し、５％の塩酸水溶液でｐＨ５に調節した
。Elemental analysis (C70,2N401S) Theoretical value: C36,21H5,21N24.13% Actual value: C36,28H5,23N24.22% Example 6 5-N-methylcarbamoyl-4-2゜2-dimethoxyethyl-1, 2,4-) riazoline-3-thione X, R = methyl, R'200- in water
(2,2-dimethoxyethyl)-1-(N-methyloxamoyl)-3-thiosemicarbazide 26.4 g (0
, 1 mol) and 9.2 g of sodium bicarbonate (0,11
After reacting at 90±10° C. for 1 hour, the reaction solution was cooled and adjusted to pH 5 with a 5% aqueous hydrochloric acid solution.
この時析出した固体を濾過し、炉液をＭＥＫ３００ｍｔ
’で抽出し、ＭＥＫ抽出液に濾過した固体を溶かした後
、無水芒硝で乾燥した後、減圧下で溶媒を除去し、残留
物をエタノールで結晶化し、純粋な目的化合物である白
色の固体２０．２ｇ（８２％収率）を得た。The solid precipitated at this time was filtered, and the furnace liquid was collected using 300 mt of MEK.
' After dissolving the filtered solid in the MEK extract and drying with anhydrous sodium sulfate, the solvent was removed under reduced pressure and the residue was crystallized with ethanol to form a white solid 20%, which is the pure target compound. .2 g (82% yield) was obtained.
融点：１７９−１８０℃
ＩＲ（ＫＢｒ）： ＬＦ３’７７．１２６４ｃｍ−’’
Ｈ−ＮＭＲδ （ＤＭＳＯ−ｄ’ｌ： ２．７３（ｄ、
３Ｈ，ＣＨｓ ） 、３．２６ （ｓ。Melting point: 179-180℃ IR (KBr): LF3'77.1264cm-''
H-NMRδ (DMSO-d'l: 2.73(d,
3H,CHs), 3.26 (s.
３Ｈ，ＯＣＨ，）、４．４６ （ｄ、２Ｈ。3H, OCH,), 4.46 (d, 2H.
ＣＨ，）、４．７０ （ｔ、 ＩＨ。CH,), 4.70 (t, IH.
８．８６ （ｂｑ、 ＩＨ，ＮＨ） 、（ｂｓ、
ＩＨ，Ｈ−２） 。8.86 (bq, IH, NH), (bs,
IH, H-2).
元素分析（Ｃ，Ｈ，、Ｎ、Ｏ，Ｓ）
理論値：Ｃ３９，０２Ｈ５，７３
実測値： Ｃ３９，０４Ｈ５，７８
実施例７
Ｎ２２．７５
Ｎ２２．７１
ＣＨ）
１３゜
％
％
２００−の水に４− （２，２−ジメトキシエチル）−
１−（Ｎ−エチルオキサモイル）−３−チオセミカルバ
ジド２７．８ｇ （０，１モル）と炭酸水素ナトリウム
９．２ｇ （０，１１モル）を加え、１時間９０±１０
℃で反応させた後、反応溶液を冷却し５％の塩酸水溶液
でｐＨ５に調節した。Elemental analysis (C, H,, N, O, S) Theoretical value: C39,02H5,73 Actual value: C39,04H5,78 Example 7 N22.75 N22.71 CH) 13°% % 200- in water 4-(2,2-dimethoxyethyl)-
27.8 g (0.1 mol) of 1-(N-ethyloxamoyl)-3-thiosemicarbazide and 9.2 g (0.11 mol) of sodium bicarbonate were added, and the mixture was heated at 90 ± 10 mol for 1 hour.
After reacting at °C, the reaction solution was cooled and adjusted to pH 5 with a 5% aqueous hydrochloric acid solution.
この時析出した固体をｔ濾過し、炉液をＭＥＫ３００−
で抽出し、ＭＥＫ抽出液に濾過した固体を溶かした後、
無水芒硝で乾燥した後、減圧下で溶媒を除去し、残留物
をエタノールで結晶化し、純粋な目的化合物である白色
の固体２１．１ｇ（８１％収率）を得た。The solid precipitated at this time was filtered, and the furnace liquid was collected using MEK300-
After dissolving the filtered solid in the MEK extract,
After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the residue was crystallized with ethanol to obtain 21.1 g (81% yield) of a white solid, the pure target compound.
融点： １３６−１３７℃
ＩＲ（ＫＢｒ）：１６８６．１２７６ｃｍ−’’Ｈ−Ｎ
ＭＲδ （ＤＭＳＯ−ｄ’）： １．１０（ｔ、３Ｈ，
ＣＨ−）、３．１９ （ｍ。Melting point: 136-137°C IR (KBr): 1686.1276cm-''H-N
MRδ (DMSO-d'): 1.10 (t, 3H,
CH-), 3.19 (m.
２Ｈ，ＮＣＨ２）、３．２３ （ｓ、６Ｈ。2H, NCH2), 3.23 (s, 6H.
ＯＣＨ，）、４．４６ （ｄ、２Ｈ。OCH, ), 4.46 (d, 2H.
ＣＨｉ）、４．６０ （ｔ、ＩＨ，ＣＨ）、８．９２
（ｂｔ、ＩＨ，ＮＨ）、１３．２（ｓ、ＩＨ，Ｈ−２）
。CHi), 4.60 (t, IH, CH), 8.92
(bt, IH, NH), 13.2 (s, IH, H-2)
.
元素分析（Ｃ，Ｈ，、Ｎ４０．Ｓ）
理論値： Ｃ４１，５３Ｈ６，１９Ｎ２１．５２％実測
値： Ｃ４１，４８Ｈ６，２８Ｎ２１．４５％実施例８
トリアゾリン−３−チオンの製 Ｘ、Ｒ＝シクロプロ
ピル、Ｒ’ ＝メトキシ
２００ｍ１’の水に４− （２，２−ジメトキシエチル
）−１−（Ｎ−シクロプロピルオキサモイル）−３−チ
オセミカルバジド２９．０ｇ （０，１モル）と炭酸水
素ナトリウム９．２ｇ （０，１１モル）を加え、１時
間９０±１０℃で反応させた後１反応溶液を冷却し、５
％塩酸水溶液でｐＨ５に調節した。Elemental analysis (C, H,, N40.S) Theoretical value: C41,53H6,19N21.52% Actual value: C41,48H6,28N21.45% Example 8 Preparation of triazoline-3-thione X, R = cyclopropyl , R' = methoxy 29.0 g (0.1 mol) of 4-(2,2-dimethoxyethyl)-1-(N-cyclopropyloxamoyl)-3-thiosemicarbazide and 9 mol of sodium bicarbonate in 200 ml of water After adding .2g (0.11 mol) and reacting at 90±10°C for 1 hour, the reaction solution was cooled and 5.
The pH was adjusted to 5 with % aqueous hydrochloric acid solution.
この時析出した固体を濾過し、炉液をＭＥＫ３００ｍｔ
’で抽出し、ＭＥＫ抽出液に濾過した固体を溶かした後
、無水芒硝で乾燥した後、減圧下で溶媒を除去し、残留
物をエタノールで結晶化し、純粋な目的化合物である白
色の固体２３．１ｇ（８５％収率）を得た。The solid precipitated at this time was filtered, and the furnace liquid was collected using 300 mt of MEK.
After extracting with .1 g (85% yield) was obtained.
融点：１６２−１６３℃
ＩＲ（ＫＢｒ）：１６５８．１２６５ｃｍ−’’Ｈ−Ｎ
ＭＲδ （ＤＭＳＯ−ｄ’ｌ： ０．６６（ｍ、４Ｈ，
シクロプロピル）、２．７６（ｍ、ｌＨ，シクロプロピ
ル）、３．３０（ｃ に ロ ｎ 「 ロ
− ） り Ｇ つ ｒ ←２Ｈ，ＣＨ，）
、４． ６２ （ｔ、 ＩＨ。Melting point: 162-163℃ IR (KBr): 1658.1265cm-''H-N
MRδ (DMSO-d'l: 0.66(m, 4H,
cyclopropyl), 2.76 (m, lH, cyclopropyl), 3.30 (c ni ro n ``ro
− ) ri G Tsu r ←2H,CH,)
,4. 62 (t, IH.
ＣＨ）、８．０６ （ｂｔ、 ＩＨ，ＮＨ） 、
８、 ８９ （ｄ、 ＩＨ，Ｃ０ＮＨＣ） 、１
０．０９ （ｂｓ、２Ｈ，ＮＨＮＨ） 。CH), 8.06 (bt, IH, NH),
8, 89 (d, IH, C0NHC), 1
0.09 (bs, 2H, NHNH).
元素分析（Ｃ８゜Ｈ１６Ｎ ４０３Ｓ ）理論値：Ｃ４
４，１１Ｈ５，９２Ｎ２０．５７％実測値： Ｃ４４，
０８Ｈ６，０１Ｎ２０．４８％実施例９
２００−の水に５−カルバモイル−４−（２゜２−ジメ
トキシエチル）−１，２，４−トリアゾリン−３−チオ
ン１１．６ｇ （０，０５モル）と５％塩酸水溶液５５
ｍｔ’ （０，０７５モル）を加え、２時間還流反応さ
せた後、反応溶液を冷却すると結晶が析出した。析出し
た固体を濾過し、５０−の冷水で洗浄した後、水で再結
晶して純粋な目的化合物である白色の固体６．６ｇ （
７９％１（σ忠） ルｊ員す〜
融点：２９０℃以上
ＩＲ（ＫＢｒ）：１６８９．１２８９ｃｍ−’’Ｈ−Ｎ
ＭＲδ （ＤＭＳＯ−ｄ’）： ｅ、８９（ｔ、ＬＨ，
Ｈ−６）、７．１７ （ｄ。Elemental analysis (C8°H16N 403S) Theoretical value: C4
4,11H5,92N20.57% Actual value: C44,
08H6,01N20.48% Example 9 11.6 g (0.05 mol) of 5-carbamoyl-4-(2゜2-dimethoxyethyl)-1,2,4-triazoline-3-thione was added to 200 ml of water. 5% aqueous hydrochloric acid solution 55
mt' (0,075 mol) was added and the reaction solution was refluxed for 2 hours. When the reaction solution was cooled, crystals were precipitated. The precipitated solid was filtered, washed with 50-degree cold water, and then recrystallized with water to obtain 6.6 g of a white solid, which is the pure target compound (
79%1 (σ) Melting point: 290℃ or higher IR (KBr): 1689.1289cm-''H-N
MRδ (DMSO-d'): e, 89 (t, LH,
H-6), 7.17 (d.
ＩＨ，Ｈ−５） 、１１．４７ （ｓ、ＬＨ。IH, H-5), 11.47 (s, LH.
Ｈ−７）、１４．７６ （ｂｓ、ＬＨ，Ｈ−２）。H-7), 14.76 (bs, LH, H-2).
元素分析（ＣｓＨ４Ｎ４０Ｓ）
理論値： Ｃ３５，７２Ｈ２，４０Ｎ３３．３２％実測
値： Ｃ３５，６３Ｈ２，３０Ｎ３３．１４％実施例１
０
＝メチル
２００−の水に５−（Ｎ−カルバモイル）−４−（２，
２−ジメトキシエチル）−１，２，４−トリアゾリン−
３−チオン１２．３ｇ （０，０５モル）と５％塩酸水
溶液５５ｍｔＪ（０，０７５モル）を加え、２時間還流
反応させた後、反応溶液を冷却すると結晶が析出した。Elemental analysis (CsH4N40S) Theoretical value: C35,72H2,40N33.32% Actual value: C35,63H2,30N33.14% Example 1
5-(N-carbamoyl)-4-(2,
2-dimethoxyethyl)-1,2,4-triazoline-
12.3 g (0.05 mol) of 3-thione and 55 mtJ (0.075 mol) of a 5% aqueous hydrochloric acid solution were added, and the mixture was refluxed for 2 hours. When the reaction solution was cooled, crystals were precipitated.
析出した固体を濾過し、５０−の冷水で洗浄した後、エ
タノールで再結晶して純粋な目的化合物である白色の固
体７．８ｇ （８６％収率）を得た。The precipitated solid was filtered, washed with 50-degree cold water, and then recrystallized with ethanol to obtain 7.8 g (86% yield) of a white solid, which is the pure target compound.
融点：２９０℃以上
ＩＲ（ＫＢｒ）：１６８１．１２８２ｃｍ−’’Ｈ−Ｎ
ＭＲδ （ＤＭＳＯ−ｄ’）：３．４１（ｓ、３Ｈ，Ｃ
Ｈｓ ） 、７．１２ （ｄ。Melting point: 290℃ or higher IR (KBr): 1681.1282cm-''H-N
MRδ (DMSO-d'): 3.41 (s, 3H, C
Hs), 7.12 (d.
ＬＨ，Ｈ−６）、７．２５ （ｄ、ＬＨ。LH, H-6), 7.25 (d, LH.
Ｈ−５）、１４．５４ （ｂｓ、ＩＨ，Ｈ−２）。H-5), 14.54 (bs, IH, H-2).
元素分析（Ｃ，Ｈ，Ｎ４０Ｓ）
理論値：Ｃ３９，５５Ｈ３，３２Ｎ３０．７５％実測値
：Ｃ３９，５３Ｈ３，２１Ｎ３０．６５％実施例１１
＝エチル
２００−の水に５−（Ｎ−エチルカルバモイル）−４−
（２，２−ジメトキシエチル）−１゜２．４−トリアゾ
リン−３−チオン１３．Ｏｇ（０，０５モル）と５％塩
酸水溶液５５−（０，０７５モル）を加え、２時間還流
反応させた後、反応溶液を冷却すると結晶が析出した。Elemental analysis (C, H, N40S) Theoretical value: C39,55H3,32N30.75% Actual value: C39,53H3,21N30.65% Example 11 = Ethyl 200- in water with 5-(N-ethylcarbamoyl)- 4-
(2,2-dimethoxyethyl)-1゜2.4-triazoline-3-thione 13. Og (0.05 mol) and 5% aqueous hydrochloric acid solution 55-(0.075 mol) were added and the mixture was refluxed for 2 hours. When the reaction solution was cooled, crystals precipitated.
析出した固体を濾過し、５０−の冷水で洗浄した後、エ
タノールで再結晶して純粋な目的化合物である白色の固
体８．１ｇ（８３％収率）を得た。The precipitated solid was filtered, washed with 50-degree cold water, and then recrystallized with ethanol to obtain 8.1 g (83% yield) of a white solid, which is the pure target compound.
融点： ２８５−２８６℃
ＩＲ（ＫＢｒ）：１６７４．１２８０ｃｍ−’’Ｈ−Ｎ
ＭＲδ （ＤＭＳＯ−ｄ’ｌ： ｉ、２５（ｔ、３）！
、ＣＨｉ ）、３．９１ （Ｑ。Melting point: 285-286°C IR (KBr): 1674.1280cm-''H-N
MRδ (DMSO-d'l: i, 25(t, 3)!
, CHi), 3.91 (Q.
２Ｈ，ＣＨ２）、７．２０ （ｄ、ＬＨ，Ｈ−６）、７
．２７ （ｄ、ＩＨ，Ｈ−５）、１４．７５ （ｂｓ、
ＩＨ，Ｈ−２）。2H, CH2), 7.20 (d, LH, H-6), 7
．． 27 (d, IH, H-5), 14.75 (bs,
IH, H-2).
元素分析（Ｃ−？ Ｈ６Ｎ 、 Ｏ５）理論値： Ｃ４
２，８５Ｈ４，ｌＩ Ｎ２８．５５％実測値： Ｃ
４２，８４Ｈ４，０９Ｎ２８．４５％実施例１２
７−シクロブロビルー８−オキソ−３−チオオ２００ｍ
ｔ’の水に５− （Ｎ−シクロプロピルカルバモイル）
−４−（２，２−ジメトキシエチル）−１，２，４−ト
リアゾリン−３−チオン１３．６ｇ （０，０５モル）
と５％塩酸水溶液５５ｍ１’ （０，０７５モル）を加
え、２時間還流反応させた後、反応溶液を冷却すると結
晶が析出した。Elemental analysis (C-? H6N, O5) Theoretical value: C4
2,85H4,lI N28.55% actual value: C
42,84H4,09N28.45%Example 12 7-cyclobroby-8-oxo-3-thioo 200m
5-(N-cyclopropylcarbamoyl) in water at t'
-4-(2,2-dimethoxyethyl)-1,2,4-triazoline-3-thione 13.6 g (0.05 mol)
and 55 mL (0,075 mol) of a 5% aqueous hydrochloric acid solution were added thereto and the reaction solution was refluxed for 2 hours. When the reaction solution was cooled, crystals precipitated.
析出した固体をｉ濾過して、５０−の冷水で洗浄した後
、エタノールで再結晶して純粋な目的化合物である白色
の固体８．７ｇ （８４％収率）を得た。The precipitated solid was filtered, washed with 50-degree cold water, and then recrystallized with ethanol to obtain 8.7 g (84% yield) of a white solid, which is the pure target compound.
融点： ２７９−２８０℃
ＩＲ（ＫＢｒ）：１６７８．１２８１ｃｍ−’’Ｈ−Ｎ
ＭＲδ （ＤＭＳＯ−ｄ’）： ｏ、９６（ｍ、４Ｈ、
シクロプロピル）、３．２３（ｍ、１）（、シクロプロ
ピル）、７．０２（ｄ、 ＬＨ，Ｈ−６）、７．２０
ＩＨ，Ｈ−５） 、 １３． ８５
ＩＨ，Ｈ−２）。Melting point: 279-280°C IR (KBr): 1678.1281cm-''H-N
MRδ (DMSO-d'): o, 96(m, 4H,
cyclopropyl), 3.23 (m, 1) (, cyclopropyl), 7.02 (d, LH, H-6), 7.20 IH, H-5), 13. 85 IH, H-2).
元素分析（Ｃ，Ｈ，Ｎ、Ｏ５） 理論値： Ｃ４６，１４Ｈ３，８７ 実測値： Ｃ４５，９７Ｈ３，８４ 実施例１３ Ｎ２６．９１ （ｂｓ。Elemental analysis (C, H, N, O5) Theoretical value: C46,14H3,87 Actual value: C45,97H3,84 Example 13 N26.91 (bs.
Ｎ２６．７８ （ｄ。N26.78 (d.
％
％
４− （２，２−ジメトキシエチル）−１−エチルオキ
サリル−３−チオセミカルバジド（■）２７．９ｇ （
０，１モル）を水２００ｍＺに溶かした後、２８％アン
モニア水４２−（０，３モル）を加え、１５〜３０℃で
２時間撹拌反応させた後、減圧下で過量のアンモニアを
除去した６反応溶液に炭酸水素ナトリウム９．２ｇ （
０，ｌ １モル）を加え、１時間還流反応させた後、反
応溶液を常温まで冷却し、５％塩酸水溶液１９０Ｊ（０
，２６モル）を加え、２時間再び還流反応させた。反応
溶液を冷却すると結晶が析出し、これを濾過乾燥して純
粋な目的化合物である白色の固体１１．３ｇ （６４％
収率）を得た。物理的な性質及び分光学的な性質は実施
例９の結果と同一であった。% % 4-(2,2-dimethoxyethyl)-1-ethyloxalyl-3-thiosemicarbazide (■) 27.9 g (
After dissolving 0.1 mol) in 200 mZ of water, 28% ammonia water 42-(0.3 mol) was added, and the reaction was stirred at 15 to 30°C for 2 hours, and excess ammonia was removed under reduced pressure. 6 Add 9.2 g of sodium hydrogen carbonate to the reaction solution (
After refluxing for 1 hour, the reaction solution was cooled to room temperature and added with 190 J of 5% hydrochloric acid aqueous solution (1 mol)
, 26 mol) was added thereto, and the mixture was refluxed again for 2 hours. When the reaction solution was cooled, crystals precipitated, which were filtered and dried to yield 11.3 g (64%) of a white solid, which is the pure target compound.
Yield) was obtained. The physical and spectroscopic properties were the same as those of Example 9.
実施例１４
４− （２，２−ジメトキシエチル）−１−エチルオキ
サリル−３−チオセミカルバジド（■）２７．９ｇ （
０，１モル）を水２００ｍ１’に溶かした後、４０％メ
チルアミン水溶液２６１ｎＩ！（０，３モル）を加え、
１５〜２０℃で２時間撹拌反応させた後、減圧下で過量
のメチルアミンを除去した０反応溶液に炭酸水素ナトリ
ウム９．２ｇ・（０，１１モル）を加え、１時間還流反
応させた後、反応溶液を常温まで冷却し、５％塩酸水溶
液１９０１ｄ（０，２６モル）を加え、２時間再び還流
反応させた０反応溶液を冷却すると結晶が析出し、これ
を濾過乾燥して純粋な目的化合物である白色の固体１２
．６ｇ （６９％収率）を得た。物理的な性質及び分光
学的な性質は実施例１０の結果と同一であった。Example 14 27.9 g of 4-(2,2-dimethoxyethyl)-1-ethyloxalyl-3-thiosemicarbazide (■) (
After dissolving 0.1 mol) in 200 ml of water, 261 nI of 40% methylamine aqueous solution! (0.3 mol) was added,
After reacting with stirring at 15-20°C for 2 hours, excess methylamine was removed under reduced pressure, 9.2 g (0.11 mol) of sodium hydrogen carbonate was added to the reaction solution, and the mixture was reacted under reflux for 1 hour. The reaction solution was cooled to room temperature, 5% aqueous hydrochloric acid solution 1901d (0.26 mol) was added, and the reflux reaction was carried out again for 2 hours. When the reaction solution was cooled, crystals precipitated, and these were filtered and dried to obtain the pure target. A white solid that is a compound 12
．． 6g (69% yield) was obtained. The physical and spectroscopic properties were the same as those of Example 10.
実施例１５
４− （２，２−ジメトキシエチル）−１−エチルオキ
サリル−３−チオセミカルバジド（■）２７．９ｇ （
０，１モル）を水２００−に溶かした後、７０％エチル
アミン水溶液２４ｄ（０，３モル）を加え、１５〜２０
℃で２時間撹拌反応させた後、減圧下で過量のエチルア
ミンを除去した０反応溶液に炭酸水素ナトリウム９．２
ｇ（０，１１モル）を加え、１時間還流反応させた後１
反応溶液を常温まで冷却し、５％垣醋酸水溶液１９Ｏ−
（０，２６モル）を加え、２時間再び還流反応させた。Example 15 27.9 g of 4-(2,2-dimethoxyethyl)-1-ethyloxalyl-3-thiosemicarbazide (■) (
After dissolving 0.1 mol) in 200 - of water, 24 d (0.3 mol) of a 70% aqueous ethylamine solution was added, and 15 to 20
After stirring the reaction at ℃ for 2 hours, excess ethylamine was removed under reduced pressure.
g (0.11 mol) was added and reacted under reflux for 1 hour.
The reaction solution was cooled to room temperature, and 5% aqueous acetic acid solution 19O-
(0.26 mol) was added, and the mixture was refluxed again for 2 hours.
反応溶液を冷却すると結晶が析出し、これを濾過乾燥し
て、純粋な目的化合物である白色の固体１３．３ｇ （
６８％収率）を得た。When the reaction solution was cooled, crystals precipitated, which were filtered and dried to obtain 13.3 g of a white solid, which is the pure target compound (
68% yield) was obtained.
物理的な性質及び分光学的な性質は実施例１１の結果と
同一であった。The physical and spectroscopic properties were the same as those of Example 11.
実施例１６
４− （２，２−ジメトキシエチル）−１−エチルオキ
サリル−３−チオセミカルバジド（■）２７．９ｇ （
０，１モル）を水２００ｄに溶かした後、シクロプロピ
ルアミン１７．１ｇ （０，３モル）を加え、２０〜２
５℃で３時間撹拌反応させた後、減圧下で過量のシクロ
プロピルアミンを除去した６反応溶液に炭酸水素ナトリ
ウム９．２ｇ（０，１１モル）を加え、１時間還流反応
させた後、反応溶液を常温まで冷却し、５％塩酸水溶液
１９０ｍ１’ （０，２６モル）を加え、２時間再び還
流反応させた１反応溶液を冷却すると結晶が析出し、こ
れを濾過乾燥して純粋な目的化合物である白色の固体１
４．０ｇ （６７％収率）を得た。Example 16 27.9 g of 4-(2,2-dimethoxyethyl)-1-ethyloxalyl-3-thiosemicarbazide (■) (
After dissolving 0.1 mol) in 200 d of water, 17.1 g (0.3 mol) of cyclopropylamine was added, and 20 to 2
After reacting with stirring at 5°C for 3 hours, excess cyclopropylamine was removed under reduced pressure. 9.2 g (0.11 mol) of sodium hydrogen carbonate was added to the reaction solution, and after reacting under reflux for 1 hour, the reaction was carried out. Cool the solution to room temperature, add 190 mL (0.26 mol) of 5% aqueous hydrochloric acid solution, and reflux the reaction again for 2 hours. 1. When the reaction solution is cooled, crystals precipitate, and these are filtered and dried to obtain the pure target compound. A white solid 1
4.0 g (67% yield) was obtained.
物理的な性質及び分光学的な性質は実施例１２の結果と
同一であった。The physical and spectroscopic properties were the same as those of Example 12.
Claims (1)
ピラジノン誘導体。 ▲数式、化学式、表等があります▼ （ I ） 式中、Ｒは水素原子、炭素数１〜６個のアルキル基、炭
素数３〜６個のシクロアルキル基又はアリル基を示す。 ２、式中、Ｒが水素原子、メチル基、エチル基又はシク
ロプロピル基である請求項１記載のトリアゾロピラジノ
ン誘導体。 ３、一般式（Ｘ）のトリアゾリン誘導体を酸で処理する
ことを特徴とする一般式（ I ）のトリアゾロピラジノ
ン誘導体の製造方法。 ▲数式、化学式、表等があります▼▲数式、化学式、表
等があります▼ （Ｘ）（ I ） 式（Ｘ）及び式（ I ）において、Ｒは水素 原子、炭素数１〜６個のアルキル基、炭素数３〜６個の
シクロアルキル基又はアリル基を示し、Ｒ′は炭素数１
〜４個の低級アルコキシ基を示す。 ４、一般式（VIII）のオキサリルチオセミカルバジドに
アンモニア又は一級アミンを反応させて一般式（IX）の
オキサモイルチオセミカルバジドとし、これに塩基を反
応させて一般式（Ｘ）のトリアゾリン誘導体とし、これ
を酸で処理して一般式（ I ）のトリアゾロピラジノン
誘導体を製造することを特徴とする一般式（ I ）のト
リアゾロピラジノン誘導体の製造方法。 ▲数式、化学式、表等があります▼ （VIII） ▲数式、化学式、表等があります▼ （IX） ▲数式、化学式、表等があります▼ （Ｘ） ▲数式、化学式、表等があります▼ （ I ） 一般式（ I ）、（VIII）、（IX）及び（Ｘ）において
、Ｒは請求項１と同じであり、Ｒ′は炭素数１〜４個の
低級アルコキシ基を示す。 ５、１級アミンが炭素数１〜６個のアルキルアミン、炭
素数３〜６個のシクロアルキルアミン又はアニリンであ
る請求項４記載のトリアゾロピラジノン誘導体の製造方
法。 ６、塩基が炭酸水素ナトリウム、炭酸水素カリウム、炭
酸ナトリウム、炭酸カリウム、水酸化ナトリウム、及び
水酸化カリウムの中から選定される塩基性水溶液である
請求項４又は５記載のトリアゾロピラジノン誘導体の製
造方法。 ７、酸が塩酸、硫酸及び硝酸の中から選択される酸性水
溶液である請求項４〜６のいずれか１項記載のトリアゾ
ロピラジノン誘導体の製造方法。 ８、一般式（Ｘ）で表わされるトリアゾリン誘導体。 ▲数式、化学式、表等があります▼ （Ｘ） 式中、Ｒ及びＲ′は請求項３と同じである。[Claims] 1. A novel triazolopyrazinone derivative represented by the following general formula (I). ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (I) In the formula, R represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, or an allyl group. 2. The triazolopyrazinone derivative according to claim 1, wherein R is a hydrogen atom, a methyl group, an ethyl group, or a cyclopropyl group. 3. A method for producing a triazolopyrazinone derivative of general formula (I), which comprises treating a triazoline derivative of general formula (X) with an acid. ▲There are mathematical formulas, chemical formulas, tables, etc.▼▲There are mathematical formulas, chemical formulas, tables, etc.▼ (X) (I) In formula (X) and formula (I), R is a hydrogen atom, an alkyl having 1 to 6 carbon atoms group, a cycloalkyl group having 3 to 6 carbon atoms, or an allyl group, and R' is a cycloalkyl group having 3 to 6 carbon atoms.
Indicates ~4 lower alkoxy groups. 4. Oxalylthiosemicarbazide of general formula (VIII) is reacted with ammonia or a primary amine to obtain oxamoylthiosemicarbazide of general formula (IX), and this is reacted with a base to obtain a triazoline derivative of general formula (X), which A method for producing a triazolopyrazinone derivative of general formula (I), which comprises producing a triazolopyrazinone derivative of general formula (I) by treating with an acid. ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (VIII) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (IX) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (X) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ ( I) In the general formulas (I), (VIII), (IX) and (X), R is the same as in claim 1, and R' represents a lower alkoxy group having 1 to 4 carbon atoms. 5. The method for producing a triazolopyrazinone derivative according to claim 4, wherein the primary amine is an alkylamine having 1 to 6 carbon atoms, a cycloalkylamine having 3 to 6 carbon atoms, or aniline. 6. The triazolopyrazinone derivative according to claim 4 or 5, wherein the base is a basic aqueous solution selected from sodium hydrogen carbonate, potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, and potassium hydroxide. Production method. 7. The method for producing a triazolopyrazinone derivative according to any one of claims 4 to 6, wherein the acid is an acidic aqueous solution selected from hydrochloric acid, sulfuric acid, and nitric acid. 8. Triazoline derivative represented by general formula (X). ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (X) In the formula, R and R' are the same as in claim 3.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019890005694A KR910003154B1 (en) | 1989-04-29 | 1989-04-29 | Triazolopirazinone derivatives and its preparation process |
| KR5694/1989 | 1989-04-29 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH03148281A true JPH03148281A (en) | 1991-06-25 |
| JPH07621B2 JPH07621B2 (en) | 1995-01-11 |
Family
ID=19285729
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2108995A Expired - Fee Related JPH07621B2 (en) | 1989-04-29 | 1990-04-26 | Triazolopyrazinone derivative and method for producing the same |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPH07621B2 (en) |
| KR (1) | KR910003154B1 (en) |
-
1989
- 1989-04-29 KR KR1019890005694A patent/KR910003154B1/en not_active IP Right Cessation
-
1990
- 1990-04-26 JP JP2108995A patent/JPH07621B2/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| HETEROCYCLES=1985 * |
| J.HETEROCYCL.CHEM=1986 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH07621B2 (en) | 1995-01-11 |
| KR910003154B1 (en) | 1991-05-20 |
| KR900016214A (en) | 1990-11-12 |
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