JPS5939896A - Purification of 5-methyl-7-diethylamino-s-triazolo (1,5-a) pyrimidine - Google Patents
Purification of 5-methyl-7-diethylamino-s-triazolo (1,5-a) pyrimidineInfo
- Publication number
- JPS5939896A JPS5939896A JP15005882A JP15005882A JPS5939896A JP S5939896 A JPS5939896 A JP S5939896A JP 15005882 A JP15005882 A JP 15005882A JP 15005882 A JP15005882 A JP 15005882A JP S5939896 A JPS5939896 A JP S5939896A
- Authority
- JP
- Japan
- Prior art keywords
- trapidil
- crude
- acid
- triazolo
- pyrimidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- GSNOZLZNQMLSKJ-UHFFFAOYSA-N Trapidil Chemical compound CCN(CC)C1=CC(C)=NC2=NC=NN12 GSNOZLZNQMLSKJ-UHFFFAOYSA-N 0.000 title description 35
- 238000000746 purification Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 2
- POFDSYGXHVPQNX-UHFFFAOYSA-N triazolo[1,5-a]pyrimidine Chemical compound C1=CC=NC2=CN=NN21 POFDSYGXHVPQNX-UHFFFAOYSA-N 0.000 claims 1
- 229960000363 trapidil Drugs 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- TXHUHDDZTWDOAJ-QPJJXVBHSA-N (e)-n,n-diethylbut-2-enamide Chemical compound CCN(CC)C(=O)\C=C\C TXHUHDDZTWDOAJ-QPJJXVBHSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
本発明は、５−メチル−７−ダニチルアミノ−８−トリ
アゾロ（１，５−ａ）ピリミジン（以下、トラピジルと
略称する。）の精製方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for purifying 5-methyl-7-danitylamino-8-triazolo(1,5-a)pyrimidine (hereinafter abbreviated as trapidil).
トラピジルは冠拡張剤として優れた薬効を有することが
知られている。このトラピジルを製造する方法は、例え
ば英国特許第
１１４８６２９号、特開昭５６−７’９６７４号、特開
昭５６−１０８７７２号などの公報明細書に提案されて
いる。またこれらの先行技術文献には、粗製のトラピジ
ルを各種の溶剤を用いて、抽出、１１）結晶などの諸操
作を繰り返すことによって精製しようとする試みも記載
されている。しかしながら、これらに具体的に開示され
ている方法によっても粗製のトラピジルは充分には精製
されず、例えば得られるトラピジルが着色不純物で汚染
されていたり、あるいは充分に純度が高くなく、医薬品
として供するには不充分な品質であることが多い。Trapidil is known to have excellent medicinal efficacy as a coronary dilator. This method for producing trapidil has been proposed, for example, in publications such as British Patent No. 1148629, JP-A-56-7'9674, and JP-A-56-108772. These prior art documents also describe attempts to purify crude trapidil by repeating various operations such as extraction and 11) crystallization using various solvents. However, even by the methods specifically disclosed in these publications, crude trapidil is not purified sufficiently, and for example, the resulting trapidil is contaminated with colored impurities or is not sufficiently pure to be used as a pharmaceutical product. are often of insufficient quality.
本発明者らは、粗製のトラピジルから医薬品として適合
しうる高品質の精製品を得る方法を鋭意検討した結果、
粗製のトラピジルと酸とを水の存在下に接触させる簡単
な操作により着色不純物の除去を行うことができ、従来
の方法よりも優れたトラピジルの精製法を見出し、本発
明に到達した。As a result of intensive research into methods for obtaining high-quality purified products suitable as pharmaceuticals from crude trapidil, the present inventors found that
The present invention has been accomplished by discovering a method for purifying trapidil that is superior to conventional methods, in which colored impurities can be removed by a simple operation of bringing crude trapidil into contact with an acid in the presence of water.
本発明を概説すれば、本発明は、粗製のトラピジルと酸
とを水の存在下に接触させることを特徴とする該化合物
の精製法、を要旨とするものである。To summarize the present invention, the gist of the present invention is a method for purifying crude trapidil and an acid, which is characterized by contacting the compound in the presence of water.
前記粗製のトラピジルは如何なる方法で製造されたもの
であってもよく、例えば、７位がハロゲン、メルカプト
基、アルキルメルカプト基、アルコキシル基等で置換さ
れた５−メチル−７−置換−ｓ−トリアゾロ（１，５−
ａ）ピリミジンとジエチルアミンを反応させる方法、Ｎ
、Ｎ−ジエチル酢酸アミドと６−アミノ−１，２，４−
）リアゾールとを脱水剤の存在下で反応させる方法、５
−ノ・口（またはアルコキシ）クロトン酸ジエチルアミ
ドと６−アミノ−１、，２，４−） ＩＪアゾールを縮
合剤の存在下で反応させる方法などを例示することがで
きるが、これらの方法に特定されない。The crude trapidil may be produced by any method, for example, 5-methyl-7-substituted-s-triazolo in which the 7-position is substituted with a halogen, a mercapto group, an alkylmercapto group, an alkoxyl group, etc. (1,5-
a) Method of reacting pyrimidine and diethylamine, N
, N-diethyl acetate amide and 6-amino-1,2,4-
) A method of reacting with lyazole in the presence of a dehydrating agent, 5
Examples include a method in which crotonic acid diethylamide (or alkoxy) and 6-amino-1,2,4-) IJ azole are reacted in the presence of a condensing agent; Not done.
本発明の方法において使用される酸としては、塩酸、硫
酸、リン酸などの鉱酸、ギ酸、酢酸、プロピオン酸など
の有機酸を例示することができる。Examples of acids used in the method of the present invention include mineral acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, and propionic acid.
これらの酸のうちでは、塩酸を使用することが好ましい
。これらの酸の使用量は、粗製トラピジルに対して通常
０．１ないし２０モル％の範囲、好ましくは０．５ない
し１０モル％の範囲である。前記粗製トラピジルと該酸
との接触は水の存在下で行うことが必要であり、その水
の使用量は粗製トラピジル１重量部に対し通常０゜０１
ないし５０重量部の範囲、好ましくは０・１ないし３０
重量部の範囲である。Among these acids, it is preferred to use hydrochloric acid. The amount of these acids used is usually in the range of 0.1 to 20 mol%, preferably in the range of 0.5 to 10 mol%, based on the crude trapidil. The contact between the crude Trapidil and the acid needs to be carried out in the presence of water, and the amount of water used is usually 0.01 parts by weight per 1 part by weight of the crude Trapidil.
In the range from 0.1 to 50 parts by weight, preferably from 0.1 to 30 parts by weight.
Parts by weight range.
本発明の方法において、前記粗製のトラピジルと酸とを
水の存在下に接触処理する際、粗製トラピジルは溶液状
態であることが好適であり、水溶液または酸およびトラ
ピジルに対して不活性な有機溶媒の溶液としておくこと
が好ましい。前記粗製のトラピジルを有機溶媒溶液のＪ
し態で使用する際、その有機溶媒は水と混和しない溶媒
の溶液であることが好ましい。該有機溶媒としては、ヘ
キサン、ヘプタン、ベンゼン、トルエン、キシレンなど
の炭化水素、１，２−ジクロロエタン、ジクロロメタン
、クロロホルム、クロロベンゼンなどのノーロゲン化炭
化水素、ジエチルエーテル、ジイソプロピルエーテルな
どのエーテル、メタノール、エタノール飄イソプロパツ
ールなどのアルコ−ルナ。In the method of the present invention, when the crude trapidil and the acid are brought into contact with each other in the presence of water, it is preferable that the crude trapidil is in a solution state, and the crude trapidil is preferably in the form of an aqueous solution or an organic solvent inert to the acid and trapidil. It is preferable to use a solution of The crude Trapidil was added to J
When used in a liquid state, the organic solvent is preferably a solution of a water-immiscible solvent. Examples of the organic solvent include hydrocarbons such as hexane, heptane, benzene, toluene, and xylene, norogenated hydrocarbons such as 1,2-dichloroethane, dichloromethane, chloroform, and chlorobenzene, ethers such as diethyl ether and diisopropyl ether, methanol, and ethanol. Alcohol such as isopropyl alcohol.
どを例示することができる。該溶媒は単独溶媒として用
いることができるほか、２柾類以−トの混合溶媒系であ
ｐてもよい。これらの有機溶媒のうちでは、炭化水素が
好適に使用される。What can be exemplified? The solvent can be used as a single solvent or in a mixed solvent system of two or more solvents. Among these organic solvents, hydrocarbons are preferably used.
本発明の方法において、粗製トラピジルと酸との接触は
攪拌、輝盪などの手段により実施される。In the method of the present invention, contact of crude trapidil with an acid is carried out by stirring, shaking, or the like.
接触処理の際の温度は、通常２０ないし１００°Ｃ１好
ましくは４０ないし９０℃の範囲である。接触処理の際
の時間は、通常１時間以内で充分精製効果をあげること
ができる。The temperature during the contact treatment is usually in the range of 20 to 100°C, preferably 40 to 90°C. The time required for the contact treatment is usually one hour or less to achieve a sufficient purification effect.
本発明の方法において、酸と接触させたのちの混合物に
、常法たとえば抽出、晶析操作を施すことにより、医薬
品として適合しうる高度に精製され、着色度のきわめて
低い精製トラピジルを得ることができる。In the method of the present invention, it is possible to obtain purified trapidil, which is highly purified and has an extremely low degree of coloration and is suitable as a pharmaceutical, by subjecting the mixture to contact with an acid and then subjecting it to conventional methods such as extraction and crystallization. can.
次に、本発明の方法を実施例により具体的に説明する。Next, the method of the present invention will be specifically explained using examples.
参考例１〔粗トラピジルの製法〕
５−、メチル−７−ヒドロキシ−８−トリアゾロ（ｉｔ
ｓ−ａ）ピリミジン１５０ｇ％ジクロロエタン３００ｍ
＃、オキシ塩化リン１６８ｇを窒素雰囲気下５．５時間
攪拌した。その反応混合物を炭酸水素ナトリウム４２０
ｇと水１．５４の中に５０°Ｃで滴下し、０・５時間攪
拌したのち、クロロホルム５００ ｍｅで抽出した。そ
の有機層の中に、ジエチルアミン１６１ｇを滴下し５０
°Ｃで１時間攪拌した。反応混合物を水５００Ｊで洗浄
し、有機層を減圧濃縮することにより、純度９４％の粗
製トラピジル１６４ｇが得られた。この粗製トラピジル
は橙赤色に着色しており、４２７ｎｍにおける吸光度Ｅ
１％（４２７ｎｍ）は１．０２ Ｃ１ｎ
であった。Reference Example 1 [Production method of crude trapidil] 5-, methyl-7-hydroxy-8-triazolo (it
s-a) Pyrimidine 150g% dichloroethane 300m
#, 168 g of phosphorus oxychloride was stirred for 5.5 hours under a nitrogen atmosphere. The reaction mixture was mixed with 420% sodium bicarbonate.
The mixture was added dropwise to 1.54 g of water at 50°C, stirred for 0.5 hours, and then extracted with 500 me of chloroform. 161 g of diethylamine was added dropwise into the organic layer for 50 min.
Stirred at °C for 1 hour. The reaction mixture was washed with 500 J of water, and the organic layer was concentrated under reduced pressure to obtain 164 g of crude trapidil with a purity of 94%. This crude trapidil is colored orange-red and has an absorbance of E at 427 nm.
1% (427 nm) was 1.02 C1n.
実施例１
参考例１で製造ｌ、た粗製トラピジル５０．を１００ｍ
５の水に溶かしたのち３６％塩ＬＷ Ｏ１５ｍｌを加え
、キシレン２００ｇとともに８０’Ｃで１５分間激しく
攪拌した。１０分間静置後分液し、有機層を８０重量％
濃縮した。２０°Ｃに攪拌冷却し析出した結晶を戸別し
た。その結晶をキシレンから再結晶することにより、１
０％水溶液のハーゼン数（以下、単にハーゼン数と略記
）３０、純度９９．５％の無色のトラピジル３５ｇが得
られた。Example 1 Crude trapidil prepared in Reference Example 1 50. 100m
After dissolving No. 5 in water, 15 ml of 36% salt LWO was added, and the mixture was vigorously stirred with 200 g of xylene at 80'C for 15 minutes. After standing for 10 minutes, separate the organic layer to 80% by weight.
Concentrated. The mixture was stirred and cooled to 20°C, and the precipitated crystals were collected from door to door. By recrystallizing the crystal from xylene, 1
35 g of colorless trapidil with a 0% aqueous solution having a Hazen number (hereinafter simply referred to as Hazen number) of 30 and a purity of 99.5% was obtained.
比較例１
実施例１において粗トラピジルを３６％塩酸で処理する
ことなく処理する以外は同様の方法で実施した場合には
、ハーゼン数２００、純度９９．２％の微黄色のトラピ
ジル３５ｇが得られた。Comparative Example 1 When the same method as in Example 1 was carried out except that the crude trapidil was not treated with 36% hydrochloric acid, 35 g of slightly yellow trapidil with a Hazen number of 200 and a purity of 99.2% was obtained. Ta.
実施例２
実施例１において３６％塩酸１ｍｎを用いる以外は同様
の方法で処理したところ、ハーゼン数２５、純度９９．
７％の無色のトラピジル３２ｇが得られた。Example 2 When treated in the same manner as in Example 1 except that 1 ml of 36% hydrochloric acid was used, the Hazen number was 25 and the purity was 99.
32 g of 7% colorless trapidil were obtained.
実施例３〜４
実施例１において表１の酸を用いる以外は同様の方法で
処理したところ、無色のトラピジルが得られた。Examples 3 to 4 Colorless trapidil was obtained by treating in the same manner as in Example 1 except for using the acid shown in Table 1.
表 １
実施例５
参考例１に記載した粗製トラピジル５０ｇをキシレン２
００ｇに溶かし、１Ｎ塩酸５ｍｌとともに８０°Ｃで１
５分間攪拌したのち分液した。有機層を８０重量％濃縮
したのち２０℃に冷却し、析出した結晶を戸別した。そ
の結晶をキシレンから再結晶することにより、１０％水
溶液のハーゼン数３０、純度９９．５％の無色のトラピ
ジル３３ｇが得られた。Table 1 Example 5 50 g of crude trapidil described in Reference Example 1 was mixed with xylene 2
00g and 1% at 80°C with 5ml of 1N hydrochloric acid.
After stirring for 5 minutes, the liquid was separated. After concentrating the organic layer by 80% by weight, it was cooled to 20° C., and the precipitated crystals were collected from door to door. By recrystallizing the crystals from xylene, 33 g of colorless trapidil with a 10% aqueous solution having a Hazen number of 30 and a purity of 99.5% was obtained.
比較例２
実施例５において１Ｎ塩酸の代わりに水５ｍ５を用いて
攪拌し分液する以外は同様の方法で処理した場合には、
１０％水溶液のハーゼン数２５０、純度９９．２％の微
黄色トラピジル３５ｇが得られた。Comparative Example 2 When treated in the same manner as in Example 5 except that 5 m5 of water was used instead of 1N hydrochloric acid and the liquid was separated by stirring,
35 g of slightly yellow trapidil, a 10% aqueous solution with a Hazen number of 250 and a purity of 99.2%, was obtained.
実施例６〜７
実施例５においてＩＮＨＣｅを用いる代わりに表２の酸
を用いる以外は同様の方法で処理したところ、無色のト
ラピジルが得られた。Examples 6 to 7 Colorless trapidil was obtained in the same manner as in Example 5 except that the acid shown in Table 2 was used instead of INHCe.
表 ２ 出願人 三井石油化学工業株式会社 代理人 山 口 和Table 2 Applicant: Mitsui Petrochemical Industries, Ltd. Agent Kazu Yamaguchi
Claims (1)
−トリアゾロ（１，５−ａ ）ピリミジンと酸とを水の
存在下に接触させることを特徴とする該化合物の精製法
。(1) Crude 5-methyl-7-ethylamino-8
- A method for purifying the compound, which comprises bringing triazolo(1,5-a)pyrimidine into contact with an acid in the presence of water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15005882A JPS5939896A (en) | 1982-08-31 | 1982-08-31 | Purification of 5-methyl-7-diethylamino-s-triazolo (1,5-a) pyrimidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15005882A JPS5939896A (en) | 1982-08-31 | 1982-08-31 | Purification of 5-methyl-7-diethylamino-s-triazolo (1,5-a) pyrimidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS5939896A true JPS5939896A (en) | 1984-03-05 |
Family
ID=15488583
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15005882A Pending JPS5939896A (en) | 1982-08-31 | 1982-08-31 | Purification of 5-methyl-7-diethylamino-s-triazolo (1,5-a) pyrimidine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5939896A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104610266A (en) * | 2015-01-14 | 2015-05-13 | 湖北美林药业有限公司 | Trapidil compound and pharmaceutical composition thereof |
-
1982
- 1982-08-31 JP JP15005882A patent/JPS5939896A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104610266A (en) * | 2015-01-14 | 2015-05-13 | 湖北美林药业有限公司 | Trapidil compound and pharmaceutical composition thereof |
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