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 |
---|---|
KR900016214A (en) | 1990-11-12 |
JPH07621B2 (en) | 1995-01-11 |
KR910003154B1 (en) | 1991-05-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE69815126T2 (en) | PYRIMID DERIVATIVES AND METHOD FOR THE PRODUCTION THEREOF | |
JPH0371431B2 (en) | ||
JPH07196621A (en) | One-pot production of 3-quinolonecarboxylic acid derivative | |
US11414388B2 (en) | Crystal form of 3-(4-methyl-1h-imidazol-1-yl)-5-trifluoromethylaniline monohydrochloride and use thereof | |
JPH02279672A (en) | 2-alkyl-4-arylmethylaminoquinoline | |
EP0009384A1 (en) | Processes for the preparation of triazinones and condensed triazinones, and compounds so obtained | |
JPH0314566A (en) | Benzimidazole derivative | |
JP4390861B2 (en) | Synthesis of acridine derivative multidrug resistance inhibitors | |
JPH03148281A (en) | Triazolopyrazinone derivative and its preparation | |
JP2003508517A (en) | Intermediates for the preparation of quinolone carboxylic acid derivatives | |
JP2668816B2 (en) | Process for producing benzothiadiazole derivative | |
JPS63179856A (en) | Production of quinolonecarboxylic acid derivative and intermediate thereof | |
JPS61293963A (en) | 1-cycloalkene-1-carboxyamide derivative,sulfoxide thereof, manufacture and use | |
Bilek et al. | Cyclocondensation Reactions of Heterocyclic Carbonyl Compounds VII‡ Synthesis of some substituted benzo-[1, 2, 4] triazino [2, 3-a] benzimidazoles | |
Monge‐Vega et al. | Synthesis of some new derivatives of 4‐hydrazino‐5H‐pyridazino [4, 5‐b] indole | |
SG182438A1 (en) | Methods for the preparation of indazole-3-carboxyclic acid and n-(s)-1-azabicyclo[2.2.2]oct-3-yl-1h-indazole-3-carboxamide hydrochloride salt | |
JPS61277672A (en) | Manufacture of 6-amino-3-hydrazinopyridazine derivative | |
JP4425366B2 (en) | Process for producing N-benzyl-3-hydroxyazetidine | |
JP2685120B2 (en) | Method for producing dithiazolium salt | |
JPH08176150A (en) | Production of 5-chloro-4-(2-imidazolin-2-ylamino)-2,1,3-benzothiadiazole or its salt | |
JPH07224058A (en) | Production of 4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1h-azepin-4-yl)-1(2h)-phthalazinone or its salt | |
JPS5843969A (en) | Method and intermediate for manufacturing benzothiazine carboxamides | |
WO1994003439A1 (en) | Antiproliferative tricyclic compounds | |
CN118165004A (en) | Type-II GSK-3 beta inhibitor and preparation method and application thereof | |
JPS58103389A (en) | Novel pyrazolo-benzodiazepine derivative and preparation thereof |