JPS6018657B2 - Pyridazinone derivatives, manufacturing method of pyridazinone derivatives - Google Patents
Pyridazinone derivatives, manufacturing method of pyridazinone derivativesInfo
- Publication number
- JPS6018657B2 JPS6018657B2 JP131376A JP131376A JPS6018657B2 JP S6018657 B2 JPS6018657 B2 JP S6018657B2 JP 131376 A JP131376 A JP 131376A JP 131376 A JP131376 A JP 131376A JP S6018657 B2 JPS6018657 B2 JP S6018657B2
- Authority
- JP
- Japan
- Prior art keywords
- pyridazinone
- hydroxy
- phenyl
- pyridazinone derivatives
- methyl
- 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.)
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Description
【発明の詳細な説明】
本発明は一般式
（式中、Ｒ，はアルキル基、フェニル基、Ｒ２はアルキ
ル基、ベンジル基を表わす。DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula (wherein R represents an alkyl group or a phenyl group, and R2 represents an alkyl group or a benzyl group).
）で示される新規化合物２ーアルキルまたはフェニル−
４ーハイドロオキシー５−アルコキシまたはペンジルオ
キシ‐３（が）‐ピリダジノン誘導体およびその塩に関
するものであって、水溶性で毒性が少なく医薬品として
卓越した薬効を有する止血薬を得ることを目的とする。
本発明新規化合物（１）およびその塩の製造方法は次式
で示される。) Novel compound 2-alkyl or phenyl-
The present invention relates to 4-hydroxy-5-alkoxy or penzyloxy-3(ga)-pyridazinone derivatives and salts thereof, and aims to obtain a hemostatic agent that is water-soluble, has little toxicity, and has excellent medicinal efficacy as a pharmaceutical.
The method for producing the novel compound (1) of the present invention and its salt is shown by the following formula.
（式中、Ｒ，はアルキル基、フェニル基、Ｒ２及びＲ３
はアルキル基、ベンジル基を表わす）則ち、２‐置換‐
３（が）‐ピリダジノン誘導体（Ｄ）を有機塩基の存在
又は不在下で酸あるいはアルコラートと０．５及至数１
０時間加熱反応することにより容易に好収率で製造され
る。(In the formula, R is an alkyl group, a phenyl group, R2 and R3
represents an alkyl group or a benzyl group), that is, 2-substituted-
3(g)-pyridazinone derivative (D) with an acid or alcoholate in the presence or absence of an organic base from 0.5 to 1
It is easily produced in good yield by performing a heating reaction for 0 hours.
本発明新規化合物（１）の製造に用いられる原料（０）
としては２−アルキル−４，５ージアルコキシあるいは
ジベンジルオキシ‐３（が）‐ピリダジノン、２−フエ
ニル−４，５−ジアルコキシあるいはジベンジルオキシ
‐３（班）‐ピリダジノン、２−アルキルまたはフエニ
ルー４ーアルコキシ−５−ペンジルオキシ−３（２Ｈ）
ーピリダジ／ンあるいは２ーアルキルまたはフエニルー
４−ペンジルオキシ−５ーアルコキシー３（汎）‐ピリ
ダジノン等が挙げられる。Raw material (0) used in the production of the novel compound (1) of the present invention
Examples include 2-alkyl-4,5-dialkoxy or dibenzyloxy-3(ga)-pyridazinone, 2-phenyl-4,5-dialkoxy or dibenzyloxy-3(ban)-pyridazinone, 2-alkyl or phenyloxy-pyridazinone. -Alkoxy-5-penzyloxy-3(2H)
-pyridazinone, 2-alkyl or phenyl-4-penzyloxy-5-alkoxy 3(pan)-pyridazinone, and the like.
これ等原料ｍ）と反応させる酸としては、ギ酸、酢酸、
プロピオン酸、酪酸等の有機酸を使用することもできる
が、通常、数パーセントから数１０パーセントの臭化水
素酸、塩酸、硫酸および硝酸等の鉱酸水溶液が用いられ
る。The acids to be reacted with these raw materials m) include formic acid, acetic acid,
Although organic acids such as propionic acid and butyric acid may be used, usually aqueous solutions of mineral acids such as hydrobromic acid, hydrochloric acid, sulfuric acid, and nitric acid are used in concentrations ranging from several percent to several tens of percent.
例えば、原料（Ｄ）を（０）のほぼ５〜１ぴ音量の４７
％臭化水素酸水溶液と１０乃至数１０分加熱すると反応
は終了する。For example, raw material (D) is 47 with a volume of approximately 5 to 1 of (0).
% hydrobromic acid aqueous solution for 10 to several tens of minutes, the reaction is completed.
袷後、水を加えて析出する目的物（１）を猿取するか、
あるいは３％アルカリ水溶液を加えて弱酸性とし、クロ
ロホルムで抽出すると７０％前後の好収率で本発明化合
物（１）が得られる。このようにして得た（１）は通常
の方法により容易に期待する塩とすることができる。ま
た、アルコラート中の反応では通常、触媒として有機塩
基あるいはアルミニウムィソプロポキシドあるいは両者
の混合物等の存在下にて反応を行なうと目的化合物（１
）の収率が向上する。例えば、原料（１）を有機塩基と
してモルホリンを含有するナトリウムェチラート中にて
、１乃至数１独特間加熱還流すると反応は終了する。冷
後析出する本発明化合物（１）のナトリウム塩を猿取す
れば良い。尚、このようにして得た（１）のナトリウム
塩は必要により通常の方法で容易に遊離塩基とすること
ができる。この際、触媒として使用される有機塩基はそ
の塩基性の強さにより限定されるものでないが通常原料
の１／１坊音量から２倍量の範囲内で使用され、ビリジ
ン、シクロヘキシルアミン、アルコールアミン、アニリ
ン、モルホリン、ピベリジン、ピロール、ピベラジン、
アルキルアミン等が挙げられるが、何らこれ等に限定さ
れることなく、反応を促進させ効果を示す有機塩基であ
れば何れでも使用できる。After lining, add water to remove the precipitated object (1), or
Alternatively, by adding a 3% alkaline aqueous solution to make it weakly acidic and extracting with chloroform, the compound (1) of the present invention can be obtained with a good yield of about 70%. (1) thus obtained can be easily converted into the expected salt by a conventional method. In addition, in the reaction in an alcoholate, the target compound (1
) yield is improved. For example, the reaction is completed by heating and refluxing the raw material (1) as an organic base in sodium ethylate containing morpholine for 1 to several 1 hours. The sodium salt of the compound (1) of the present invention that precipitates after cooling may be filtered out. The sodium salt of (1) thus obtained can be easily converted into a free base by a conventional method, if necessary. At this time, the organic base used as a catalyst is not limited by its basic strength, but is usually used in a range of 1/1 to 2 times the amount of the raw material, such as pyridine, cyclohexylamine, alcohol amine, etc. , aniline, morpholine, piverizine, pyrrole, piverazine,
Examples include alkylamines, but the base is not limited to these in any way, and any organic base that promotes the reaction and exhibits an effect can be used.
このようにして得た本発明新規化合物ＸＩ）及びその塩
の止血作用を尾静脈切断法（マウス）を用いて検討した
ところカルバゾクロムスルホン酸ナトリウム（以下ＡＣ
−１７と略す）と同等又はそれ以上のすぐれた止血効果
を示し、医薬品として有用であることが判明した。The hemostatic effect of the novel compound of the present invention (XI) and its salts thus obtained was investigated using the tail vein cutting method (in mice).
-17), and was found to be useful as a pharmaceutical product.
次に薬理実験のデータを１部記載する。Next, some data from pharmacological experiments will be described.
尾静脈切断法による止血作用
５〜６週令（２５〜３０夕）のｄｄ系雄性マウスを用い
、一群１０匹とし、更に溶媒のみを投与した対照群とカ
ルバゾクロムスルホン酸ナトリウム（ＡＣ−１７）（１
００ムタ／ｋ９）投与群を設定した。Hemostatic effect by tail vein cutting method DD male mice aged 5 to 6 weeks (25 to 30 days) were used, 10 mice per group, and a control group administered with vehicle only and a control group administered with sodium carbazocchrome sulfonate (AC-17). 1
00 Muta/k9) administration groups were established.
水溶‘性の検体（ナトリウム塩）は生理食塩水に溶解さ
せ、難溶性の検体（遊離塩基）はＴｗｅｅｎ−８０を用
いて生理食塩水に乳化させたそれぞれの被検液０．１の
‘／１０夕（１００仏夕／Ｘ９）を背皮下に注射し、３
０分後に固定箱に入れ、１側の尾静脈を鋭利なカミソリ
で傷をつけ、出血する血液を１の砂毎に猿紙に吸い取り
止血するまでの時間を測定した。止血効果は止血時間（
秒）を対照群と比較して判定した。−：対照群と大差の
ないもの十３．０〜一３．の砂±：対照群と比較し６秒
早く止血したもの十：対照群と比較し９秒早く止血した
もの什：対照群と比較し１２秒早く止血したもの川：対
照群と比較し１９秒早く止血したものＨＨ：対照群と比
較し１現砂早く止血したもの毒性はマウス１群５匹とし
、上記止血薬サンプル各々５００の９／ｋ９を腹腔内投
与し、７幼時間後における生死を判定したが、いずれの
検体にも死亡例は認められず本発明化合物の毒性は非常
に少ないものと判定できた。A water-soluble specimen (sodium salt) was dissolved in physiological saline, and a poorly soluble specimen (free base) was emulsified in physiological saline using Tween-80. 10 minutes (100 days/X9) was injected subcutaneously into the back, and 3
After 0 minutes, the animals were placed in a fixation box, the tail vein on one side was incised with a sharp razor, and the bleeding blood was sucked up onto monkey paper for each sand, and the time until the bleeding stopped was measured. The hemostatic effect is determined by the hemostasis time (
seconds) compared with the control group. -: No significant difference from the control group 13.0 to 13. Sand±: Those who stopped bleeding 6 seconds earlier than the control group Ten: Those who stopped bleeding 9 seconds earlier than the control group Ten: Those who stopped bleeding 12 seconds earlier than the control group River: Those who stopped bleeding 19 seconds earlier than the control group HH: Hemostasis stopped sooner than the control group.Toxicity: 5 mice per group, 500 9/k9 of each of the above hemostatic drug samples was administered intraperitoneally, and survival was determined after 7 hours. However, no deaths were observed in any of the specimens, and it was determined that the toxicity of the compound of the present invention was extremely low.
次に実験例を挙げて本発明化合物を説明する。Next, the compounds of the present invention will be explained by giving experimental examples.
実施例 １２ーメチルー４−ハイドロオキシー５−エト
キシ−３（汎）‐ピリダジノン‘１１４７％臭化水素酸
１２の【中に２ーメチルー４，５ージエトキシ−３（２
Ｈ）ーピリダジノン１．４夕を添加し、俗温１２０〜１
３０ｑ○で３０分加熱還流すると発応は終了する。Example 12-Methyl-4-hydroxy-5-ethoxy-3(pan)-pyridazinone'1147% Hydrobromic acid 12
H) -Add 1.4 liters of pyridazinone and bring the temperature to 120~1
The reaction is completed by heating and refluxing at 30q○ for 30 minutes.
冷後、３０％水酸化ナトリウム水溶液１０の‘を加えて
弱酸性とし、クロロホルムで抽出する。クロロホルム層
は、水洗、苧硝で乾燥後留去し、残留物をエタノールと
イソプロピルヱーテルの鷹液から再結晶すると融点１３
９−１４０００を示す２−メチル−４ーハイドロオキシ
−５ーエトキシー３（２Ｈ）ーピリダジノンの無色鱗片
晶０．８タ得る。本品の過クロル鉄反応による水酸基検
出試験は陽性である。After cooling, add 10 parts of a 30% aqueous sodium hydroxide solution to make it weakly acidic, and extract with chloroform. The chloroform layer was washed with water, dried with molasses, distilled off, and the residue was recrystallized from a solution of ethanol and isopropyl ether to give a melting point of 13.
0.8 ta of colorless scale crystals of 2-methyl-4-hydroxy-5-ethoxy-3(2H)-pyridazinone having a molecular weight of 9-14,000 was obtained. The hydroxyl group detection test of this product using perchloriron reaction was positive.
元素分析値Ｃ７日，。Elemental analysis value C7 days.
０３Ｎ２として
理論値（％） Ｃ：４９．４０，Ｈ：５．舵，Ｎ：１６
．４０実測値（％） Ｃ：４９．４１，Ｈ：５．９０．
Ｎ：１６．斑一赤外吸収スペクトル（ＫＢす宏）肌‐１
：１６５０（Ｃ＝〇）質量スペクトルｍ／ｅ：１７０（
Ｍ十）
核磁気共鳴スペクトル（ＣＤＣ１３）肌：７．６５ （
ＩＨ，ｓｉｎｇｌｅｔ，６位Ｈ）４．３５ （が，ｑ肌
ｒＭ，５位‐ＯＣＨ２Ｃ日３）３．８２ （９日，ｓｉ
ｎｇｌｅし ２位−ＮＣ比）１．４３ （汎，ｍｐｌｅ
ｔ，５位‐ＯＣＨ２ＣＨ３）尚、常法により生成した２
−メチル−４ーハィドロオキシ‐５‐ェトキシ‐３（汎
）‐ピリダジノンのナトリウム塩は融点３００ｏｏ以上
の無色針晶で次の物性を示す。Theoretical value (%) as 03N2 C: 49.40, H: 5. Rudder, N: 16
．． 40 Actual value (%) C: 49.41, H: 5.90.
N:16. Madaraichi Infrared Absorption Spectrum (KB Suhiro) Skin-1
: 1650 (C=〇) Mass spectrum m/e: 170 (
M10) Nuclear magnetic resonance spectrum (CDC13) skin: 7.65 (
IH, singlet, 6th place H) 4.35 (but, q skin rM, 5th place - OCH2C day 3) 3.82 (9th day, si
ngle 2nd position - NC ratio) 1.43 (wide, mple
t, 5th position-OCH2CH3) In addition, 2 generated by a conventional method
The sodium salt of -methyl-4-hydroxy-5-ethoxy-3(pan)-pyridazinone is colorless needle crystals with a melting point of 300 oo or higher and exhibits the following physical properties.
赤外吸収スペクトル（ＫＢ長去）仇−１： １６００（
Ｃ＝〇）核磁気共鳴スペクトル（Ｄ２０）胸：
７．８０ （ＩＨ，ｓｉｎｇｌｅし ６位Ｈ）４．１２
（犯，ｑ肌ｒ協，５位‐ＯＣＨ２Ｃ日３）３．７２ （
粕，ｓｉｎｇｌｅし ２位‐ＮＣＨ３）１．３６ （細
，ｍｐｌｅｔ，５位‐ＯＣＨ２ＣＨ凶）【２）実施例１
の本発明化合物は次の様にしても製造することができる
。Infrared absorption spectrum (KB Nagayoshi) -1: 1600 (
C=〇) Nuclear magnetic resonance spectrum (D20) Chest: 7.80 (IH, single, 6th H) 4.12
(Kan, qhada r-kyo, 5th place-OCH2C day 3) 3.72 (
Kasu, single 2nd place - NCH3) 1.36 (thin, mplet, 5th place - OCH2CH bad) [2) Example 1
The compound of the present invention can also be produced in the following manner.
すなわち金属ナトリウム０．３５夕を含むェチラート１
０の‘中に２−メチル−４，５‐ジヱトキシ‐３（汎）
‐ピリダジノン１夕およびモルホリン０．４夕を加えて
水浴中で２曲時間加熱還流すると反応は終了する。冷後
析出する結晶を櫨敬すると融点３００００以上を示す２
ーメチルー４ーハイドロオキシ−５ーェトキシ‐３（汎
）‐ピリダジノンのナトリウム塩０．６５夕を得る。実
施例 ２２ーメチルー４−ハイドロオキシ−５ーメトキ
シ‐３（汎）‐ピリダジノン‘１’ ２ーメチルー４，
５ージメトキシー３（汎）‐ピリダジノン３夕を４７％
臭化水素酸４０必中に添加し、浴温１３０ｏｏで４０分
加熱し、袷後３０％水酸化ナトリウム水溶液約４０地を
加えて弱酸性とし、クロロホルムで抽出する。i.e. 1 chelate containing 0.35% sodium metal
2-methyl-4,5-diethoxy-3 (pan) in 0'
- Add 1 night of pyridazinone and 0.4 night of morpholine and heat under reflux for 2 hours in a water bath to complete the reaction. When the crystals that precipitate after cooling are examined, they show a melting point of 30,000 or more2.
0.65% of the sodium salt of -methyl-4-hydroxy-5-ethoxy-3(pan)-pyridazinone is obtained. Example 22-methyl-4-hydroxy-5-methoxy-3(pan)-pyridazinone '1' 2-methyl-4,
47% 5-dimethoxy-pyridazinone
Add 40% hydrobromic acid to the mixture, heat for 40 minutes at a bath temperature of 130°C, add about 40% 30% aqueous sodium hydroxide solution to make it weakly acidic, and extract with chloroform.
クロロホルム層を水洗、乾燥後留去し、残留物をメタ／
ールとィソプロピルェーテルの混液から再結晶すると融
点１６０００〜１６３午０を示す２−メチル−４ーハイ
ドロオキシー５ーメトキシー３（２Ｈ）−ピリダジノン
の無色鱗片晶１．５夕を得る。元素分析値Ｃ６は０３Ｎ
２として理論値（％）： Ｃ：４６１５，Ｈ：５１６，
Ｎ：１７．９４実測値（％）： Ｃ：４６．１９，Ｈ：
５．１６，Ｎ：１７．８３赤外吸収スペクトル（ＫＢｒ
法）弧‐１：１６５５（Ｃ＝０）
核磁気共鳴スペクトル（ＣＤＣ１２）胸：７．８１ （
ＩＨ，ｓｉｎｇｌｅし ６位Ｈ）３．７０ （班，ｓｉ
ｎｇｌｅし ‐ＮＣ生）脚 〆チラート３０の‘（金属
ナトリウム１．６含有）に２ーメチルー４，５ージメト
キシ−３（が）‐ピリダジノン３夕及びモルホリン１．
２夕を加えて１虫時間加熱還流後析出する結晶を櫨敬す
ると融点３００℃以上を示す２−メチル−４ーハイドロ
オキシー５ーメトキシー３（２Ｈ）ーピリダジノンのナ
トリウム塩（無色針晶）１．４夕を得る。The chloroform layer was washed with water, dried and distilled off, and the residue was
Recrystallization from a mixture of alcohol and isopropyl ether yields 1.5 colorless scaly crystals of 2-methyl-4-hydroxy-5-methoxy-3(2H)-pyridazinone having a melting point of 16,000 to 163 mm. Elemental analysis value C6 is 03N
Theoretical value (%) as 2: C: 4615, H: 516,
N: 17.94 Actual value (%): C: 46.19, H:
5.16, N: 17.83 infrared absorption spectrum (KBr
Law) Arc-1:1655 (C=0) Nuclear magnetic resonance spectrum (CDC12) Chest: 7.81 (
IH, single 6th place H) 3.70 (group, si
(contains 1.6% of sodium metal), 2-methyl-4,5-dimethoxy-3(ga)-pyridazinone, and 1.5% of morpholine.
After heating and refluxing for 2 hours and heating under reflux for 1 hour, the precipitated crystals were examined to obtain a sodium salt of 2-methyl-4-hydroxy-5-methoxy-3(2H)-pyridazinone (colorless needle crystals) with a melting point of 300°C or higher.1.4 Get the evening.
赤外吸収スペクトル（ＫＢｒ法）弧−．：１６１０＜Ｃ
＝。Infrared absorption spectrum (KBr method) arc-. :1610<C
=.
）核磁気共鳴スペクトル（Ｄ２０）柳：
７．８１ （ＩＨ，ｓｉｎｇｌｅＬ ６位Ｈ）３．７０
（乳日，ｓｉｎｇｌｅし ２位−ＮＣは）（３｝ モ
リホリン１．０夕、アルミニウムイソプロポキシド１．
２夕を含むメチラート３０の‘（水酸化ナトリウム３．
０タ含有）に２−メチル−４．５ージメトキシ‐３（が
）‐ピリダジノン３夕を加えて１期時間加熱還流する。) Nuclear magnetic resonance spectrum (D20) Yanagi: 7.81 (IH, single L 6th position H) 3.70
(Milk day, single, 2nd place - NC) (3) Morpholine 1.0%, aluminum isopropoxide 1.0%.
20% of methylate (sodium hydroxide) containing 30% of sodium hydroxide.
2-Methyl-4.5-dimethoxy-3(g)-pyridazinone was added to the mixture (containing 0.0%) and heated under reflux for 1 hour.
冷後析出する結晶を櫨取し、５％塩酸水溶液に溶解し、
不溶物を濃別後クロロホルムで抽出する。クロロホルム
抽出液は水洗、乾燥後留去し、メタノールとノルマルヘ
キサンの混液から再結晶すると融点１６０〜１６３ｑｏ
を示す２−メチル−４ーハイドロオキシ‐５‐メトキシ
‐３（が）‐ピリダジノンの無色鱗片晶１．２夕を得る
。実施例 ３
２ーフエニルー４ーハイドロオキシー５ーエトキシー３
（２Ｈ）ーピリダジノン‘１１ ２ーフエニルー４，５
−ジエトキシー３（２Ｈ）ーピリダジノン１．０夕を４
７％臭化水素酸１０私中にて７時間加熱還流すると反応
は終了する。After cooling, the crystals precipitated were collected and dissolved in a 5% aqueous hydrochloric acid solution.
After concentrating the insoluble matter, extract with chloroform. The chloroform extract was washed with water, dried, distilled off, and recrystallized from a mixture of methanol and n-hexane, giving a melting point of 160 to 163 qo.
1.2 colorless scaly crystals of 2-methyl-4-hydroxy-5-methoxy-3(a)-pyridazinone having the following properties were obtained. Example 3 2-phenyl-4-hydroxy-5-ethoxy3
(2H)-Pyridazinone'11 2-Phenyl-4,5
-diethoxy 3(2H)-pyridazinone 1.0 4
The reaction was completed by heating under reflux in 7% hydrobromic acid for 7 hours.
反応後水を加えて析出する結晶をエタノールから再結晶
すると融点１６４〜１６５℃を示す２ーフエニル−４ー
ハイドロオキシー５−エトキシ‐３（汎）‐ピリダジノ
ンの無色鱗片晶０．５５夕を得る。本品の過クロル鉄反
応による水酸基の検出試験は陽性である元素分析値 Ｃ
，２日，２Ｎ２０３として理論値（％） Ｃ：６２．０
６ Ｈ：５．２９，Ｎ：１２．０６実測値（％） Ｃ：
６２．０３ Ｈ：５．３１，Ｎ：１１．８７赤外吸収ス
ペクトル（ＫＢｄ宏）仇‐１：３４００〜３１００（Ｏ
Ｈ），・１６５０（Ｃ＝０）質量スペクトルｍ／ｅ：２
３２（Ｍ十）核磁気共鳴スペクトル：
８．０２ （ＩＨ，ｓｉｎｇｌｅし ６位Ｈ）７．４５
（細，ｓｉｎｇｌｅＬ ２位‐Ｃ６日虫）７．３６（Ｉ
Ｈ，ｂｒｏａｄ，４位−ＯＨ）７．２４（幻，ｑ肌ｒに
ｔ，５位−ＯＣＨ２ＣＨ３）１．３１（班，ぱｉｐｉｅ
ｔ，５位‐ＯＣＨ２ＣＨはシ２−フエニルー４ーハイド
ロオキシ−５−エトキシ‐３（幻）‐ピリダジノンのナ
トリウム塩の物性を次に示す。After the reaction, water is added and the precipitated crystals are recrystallized from ethanol to obtain colorless scaly crystals of 2-phenyl-4-hydroxy-5-ethoxy-3(pan)-pyridazinone having a melting point of 164 to 165°C. The elemental analysis value of this product was positive in the hydroxyl group detection test using perchloriron reaction.
, 2nd, Theoretical value (%) as 2N203 C: 62.0
6 H: 5.29, N: 12.06 Actual value (%) C:
62.03 H: 5.31, N: 11.87 Infrared absorption spectrum (KBd Hiroshi) -1: 3400-3100 (O
H), 1650 (C=0) mass spectrum m/e:2
32 (M10) nuclear magnetic resonance spectrum: 8.02 (IH, single 6th position H) 7.45
(Single, singleL 2nd place-C6 dianthus) 7.36 (I
H, broad, 4th place - OH) 7.24 (phantom, q skin r to t, 5th place - OCH2CH3) 1.31 (group, piepie
The physical properties of the sodium salt of 2-phenyl-4-hydroxy-5-ethoxy-3(phantom)-pyridazinone are shown below.
融点３００℃以上無色粉末赤外吸収スペクトル（ＫＢｒ
法）弧−．：１６０５（Ｃ＝○）
核磁気共鳴スペクトル（ＤＭＳＯ−ＣＩ６）跡：７．４
５（ＩＨ，ｓｉｎｇｌｅし ６位Ｈ）７．３０（軸，ｍ
山ｔｉｐｌｅｔ，２位‐Ｃ６日５）４．０７（２日，ｑ
肌ｒにｔ．５位−ＯＣＨ２Ｃ日３）１．２４（祖，ｔｒ
ｉｐｌｅｔ，５位‐ＯＣＨ２ＣＨはジ‘２’原料に２ー
フェニルー４ーメトキシ−５ーェトキシ‐３（汎）‐ピ
リダジノンを用いて‘１’と同じように臭化水素酸と７
時間加熱反応すると、６５％の収率で２−フヱニルー４
−ハイド。Colorless powder infrared absorption spectrum (KBr
modulus) arc-. :1605 (C=○) Nuclear magnetic resonance spectrum (DMSO-CI6) trace: 7.4
5 (IH, single 6th position H) 7.30 (axis, m
Mountain tiplet, 2nd place - C6 day 5) 4.07 (2 day, q
skin r to t. 5th place - OCH2C day 3) 1.24 (so, tr
iplet, 5th position-OCH2CH is prepared by using 2-phenyl-4-methoxy-5-ethoxy-3(pan)-pyridazinone as the di'2' raw material and reacting with hydrobromic acid and 7 in the same way as '1'.
When the reaction is heated for several hours, the yield of 2-phenylene-4 is 65%.
- Hyde.
オキシ‐５‐ェトキシ‐３（が）‐ピリダジノンを得る
。実施例 ４
２ーフエニルー４ーハイドロオキシー５ーメトキシ‐３
（が）‐ピリダジノン４７％臭化水素酸１８叫に２−フ
エニルー４．５−ジメトキシー３（２Ｈ）−ピリダジノ
ン２．０夕を加えて５時間加熱還流後水を加えて袷後析
出する結晶をメタノールとィソプロピルェーテルの混液
から再結晶すると融点１７９〜１８０℃を示す２−フェ
ニルー４−ハイドロオキシ−５ーメトキシー３（２Ｈ）
ーピリダジノンの無色針晶１．０９を得る。Oxy-5-ethoxy-3(ga)-pyridazinone is obtained. Example 4 2-phenyl-4-hydroxy-5-methoxy-3
(2)-pyridazinone Add 2.0 ml of 2-phenyl-4.5-dimethoxy-3(2H)-pyridazinone to 18% 47% hydrobromic acid, heat under reflux for 5 hours, and then add water to remove the crystals that precipitate. 2-Phenyl-4-hydroxy-5-methoxy 3 (2H) exhibits a melting point of 179-180°C when recrystallized from a mixture of methanol and isopropyl ether.
- 1.09% of colorless needle crystals of pyridazinone are obtained.
元素分析値Ｃ，．日，ぷ２０３として理論値（％） Ｃ
：６０．５５ Ｈ：４．６２’Ｎ：１２．８４実測値（
％） Ｃ：６０．７４，Ｈ：４．８０，Ｎ：１３．１２
赤外吸収スペクトル（ＫＢｒ法）ｃの‐１： ３３００
〜３００（ＯＨ），１６５０（Ｃ＝○）質量 スペクト
ルｍ／ｅ：２１８（Ｍ十）核磁気共鳴スペクトル（ＤＭ
ＳＯ−ＣＩ６）柳：３．９６（祖，ｓｉｎｇｌｅし ５
位‐ＯＣＨ３）７．５０（斑，ｓｉｎｇｌｅし ２位‐
Ｃ６日虫）８．１５（ＩＨ，ｓｉｎｇｌｅＬ ６位Ｈ）
１０．１８（ＩＨ，ｂｒｏａｄ，４位一〇Ｈ）次に実施
例１と同じようにして合成した本発明化合物の物性を一
括して示す。Elemental analysis value C,. Theoretical value (%) C
:60.55 H:4.62'N:12.84 Actual value (
%) C: 60.74, H: 4.80, N: 13.12
Infrared absorption spectrum (KBr method) c-1: 3300
~300 (OH), 1650 (C=○) Mass spectrum m/e: 218 (M10) Nuclear magnetic resonance spectrum (DM
SO-CI6) Yanagi: 3.96 (so, single 5)
2nd place - OCH3) 7.50 (spotted, single)
C6 dianthus) 8.15 (IH, single L 6th H)
10.18 (IH, broad, 4th position 10H) Next, the physical properties of the compound of the present invention synthesized in the same manner as in Example 1 will be summarized.
Claims (1)
アルキル基、ベンジル基を表わす。 ）で示されるピリダジノン誘導体およびその塩。２ 一
般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＿１はアルキル基、フエニル基、Ｒ＿２及
びＲ＿３はアルキル基、ベンジル基を表わす。 ）で示されるピリダジノン誘導体を有機塩基の存在下又
は不存在下で酸あるいはアルコラートと反応させること
を特徴とする、一般式▲数式、化学式、表等があります
▼ （式中、Ｒ＿１はアルキル基、フエニル基、Ｒ＿２は
アルキル基、ベンジル基を表わす。 ）で示されるピリダジノン誘導体およびその塩の製造法
。[Claims] 1. Pyridazinone derivatives and their salts represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. . 2. A pyridazinone derivative represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. There are general formulas ▲mathematical formulas, chemical formulas, tables, etc.▼ that are characterized by reacting with an acid or alcoholate in the absence of the compound. ) A method for producing a pyridazinone derivative and its salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP131376A JPS6018657B2 (en) | 1976-01-05 | 1976-01-05 | Pyridazinone derivatives, manufacturing method of pyridazinone derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP131376A JPS6018657B2 (en) | 1976-01-05 | 1976-01-05 | Pyridazinone derivatives, manufacturing method of pyridazinone derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5285181A JPS5285181A (en) | 1977-07-15 |
| JPS6018657B2 true JPS6018657B2 (en) | 1985-05-11 |
Family
ID=11498000
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP131376A Expired JPS6018657B2 (en) | 1976-01-05 | 1976-01-05 | Pyridazinone derivatives, manufacturing method of pyridazinone derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6018657B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0528931Y2 (en) * | 1987-01-30 | 1993-07-26 |
-
1976
- 1976-01-05 JP JP131376A patent/JPS6018657B2/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0528931Y2 (en) * | 1987-01-30 | 1993-07-26 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5285181A (en) | 1977-07-15 |
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