JPH0328421B2 - - Google Patents
Info
- Publication number
- JPH0328421B2 JPH0328421B2 JP7109782A JP7109782A JPH0328421B2 JP H0328421 B2 JPH0328421 B2 JP H0328421B2 JP 7109782 A JP7109782 A JP 7109782A JP 7109782 A JP7109782 A JP 7109782A JP H0328421 B2 JPH0328421 B2 JP H0328421B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- present
- cyano
- methylamine
- guanidine
- 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.)
- Expired
Links
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 150000002357 guanidines Chemical class 0.000 claims description 3
- OWGYZXRIBLNBAU-UHFFFAOYSA-N 2-methyl-1-(2-sulfanylethyl)guanidine Chemical compound CN=C(N)NCCS OWGYZXRIBLNBAU-UHFFFAOYSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 238000000862 absorption spectrum Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 229960003151 mercaptamine Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZORWZOOZJGMSTE-UHFFFAOYSA-N 1-cyano-2-methyl-3-(2-sulfanylethyl)guanidine Chemical compound N#CNC(=NC)NCCS ZORWZOOZJGMSTE-UHFFFAOYSA-N 0.000 description 1
- GAPFINWZKMCSBG-UHFFFAOYSA-N 2-(2-sulfanylethyl)guanidine Chemical compound NC(=N)NCCS GAPFINWZKMCSBG-UHFFFAOYSA-N 0.000 description 1
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- AQIXAKUUQRKLND-UHFFFAOYSA-N cimetidine Chemical compound N#C/N=C(/NC)NCCSCC=1N=CNC=1C AQIXAKUUQRKLND-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229940097265 cysteamine hydrochloride Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- -1 imide compound Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- MHGGQXIPBPGZFB-UHFFFAOYSA-N methyl n-cyano-n'-methylcarbamimidothioate Chemical compound CSC(=NC)NC#N MHGGQXIPBPGZFB-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は、グアニジン誘導体、特に下式〔〕
で示されるＮ−シアノ−N′−メチル−N″−（２−
メルカプトエチル）グアニジンの製造方法に関す
る。DETAILED DESCRIPTION OF THE INVENTION The present invention provides guanidine derivatives, particularly the following formula []
N-cyano-N'-methyl-N''-(2-
The present invention relates to a method for producing (mercaptoethyl) guanidine.
本発明の目的化合物〔〕は、H2受容体に対
する拮抗作用を有する下式〔〕の化合物（一般
名を「シメチジン」と称する）の合成に有用な化
合物である。 The object compound [ ] of the present invention is a compound useful in the synthesis of a compound of the following formula [ ] (general name is "cimetidine") which has an antagonistic effect on H 2 receptors.
従来、上記グアニジン誘導体〔〕の製造法と
しては、ジメチルシアノジチオイミドカーボネー
ト〔〕
とメチルアミン〔〕
CH3NH2 〔〕
を反応させて、Ｎ−シアノ−N′，Ｓ−ジメチル
イソチオウレア〔〕
を得て、これをシステアミン〔〕
HSCH2CH2NH2 〔〕
と反応させて化合物〔〕を得るものであつた。 Conventionally, as a method for producing the above guanidine derivative [], dimethylcyanodithioimide carbonate [] and methylamine [] CH 3 NH 2 [] to form N-cyano-N',S-dimethylisothiourea [] This was then reacted with cysteamine [] HSCH 2 CH 2 NH 2 [] to obtain the compound [].
しかしながら、上記のように化合物〔〕を経
由して目的化合物〔〕を得る方法（特開昭51−
125074号等）では収率が低く、工業的製法として
満足し得るものとは言い難い。 However, as mentioned above, the method of obtaining the target compound [] via the compound []
No. 125074, etc.), the yield is low and it is difficult to say that it is a satisfactory industrial production method.
本発明は上記従来法と異なり、イミド化合物
〔〕をシステアミン〔〕と反応させて得られ
る下式〔〕で示されるＮ−シアノ−N′，Ｓ−
エチレンイソチオウレア
を原料化合物とし、これをメチルアミン〔と反
応させることにより目的化合物であるイミダゾー
ル誘導体〔〕を得るものである。 The present invention differs from the above conventional method in that the N-cyano-N',S-
Ethyleneisothiourea is used as a raw material compound, and by reacting it with methylamine, the target compound, an imidazole derivative, is obtained.
従来、本発明のように化合物〔〕を使用する
イミダゾール誘導体〔〕の製造例は見当らない
が、それは化合物〔XII〕が安定な５員環を形成し
ているためアミン類と反応させることは困難であ
るとの通念があつたからであろう。本発明者等
は、メチルアミンを使用すれば、容易に置換反応
が生じ、目的とする化合物〔〕が得られること
を見出した。 Until now, there have been no examples of production of imidazole derivatives [ ] using compound [ ] as in the present invention, but because compound [XII] forms a stable 5-membered ring, it is difficult to react with amines. This is probably because there was a common belief that it was. The present inventors have found that when methylamine is used, a substitution reaction easily occurs and the desired compound [ ] can be obtained.
本発明によれば、化合物〔〕とメチルアミン
〔〕とを、溶媒、例えばメタノール、エタノー
ル、などの溶媒中、常温ないし加温（30〜60
℃）・常圧下に、効率よく反応させ、前記従来法
に比しはるかに高収率で目的化合物〔〕を得る
ことができる。 According to the present invention, the compound [ ] and methylamine [ ] are mixed in a solvent such as methanol, ethanol, etc. at room temperature or heated (30 to 60 °C).
℃)・The reaction can be carried out efficiently under normal pressure, and the target compound [ ] can be obtained in a much higher yield than in the conventional method.
なお、原料化合物〔〕は、イミド化合物
〔〕とシステアミン〔〕またはその塩とを、
エタノールなどの溶媒中、常温・常圧で反応させ
ることにより容易に得られる。 In addition, the raw material compound [] is an imide compound [] and cysteamine [] or its salt,
It can be easily obtained by reacting in a solvent such as ethanol at room temperature and pressure.
下記に本発明の実施例を挙げるが、本発明はこ
れに限定されるものではない。 Examples of the present invention are listed below, but the present invention is not limited thereto.
実施例
Ｎ−シアノ−N′−メチル−N″−（２−メルカプ
トエチル）グアニジン〔〕の製造：
Ｎ−シアノ−N′，Ｓ−エチレンイソチオウレ
ア〔〕１ｇ（このものの合成は参考例参照）を
メチルアミンの30％エタノール溶液30mlに加え、
50℃で３時間反応させる。反応液を留去し、残渣
に水を加え、PH８に調節して酢酸エチルと振とう
する。水相をPH４に調節したのち、再び酢酸エチ
ルと振とうする。酢酸エチル相を得、乾燥後溶媒
を留去して目的化合物〔〕を得る。収量1.17ｇ
（95％）。Example Production of N-cyano-N'-methyl-N''-(2-mercaptoethyl)guanidine []: 1 g of N-cyano-N',S-ethyleneisothiourea [] (For the synthesis of this product, see Reference Example) was added to 30 ml of a 30% ethanol solution of methylamine,
React at 50°C for 3 hours. The reaction solution was distilled off, water was added to the residue, the pH was adjusted to 8, and the mixture was shaken with ethyl acetate. After adjusting the aqueous phase to PH4, it is again shaken with ethyl acetate. An ethyl acetate phase is obtained, and after drying, the solvent is distilled off to obtain the target compound [ ]. Yield 1.17g
(95%).
第１図に赤外吸収スペクトルを示す。 Figure 1 shows the infrared absorption spectrum.
参考例
Ｎ−シアノ−N′，Ｓ−エチレンイソチオウレ
ア〔〕の合成：
ジメチルシアノジチオイミドカーボネート10ｇ
（0.0685モル）とシステアミン塩酸塩6.8ｇ
（0.0685モル）およびトリエチルアミン6.9ｇ
（0.0685モル）をエタノール100mlに加え室温で３
〜４時間撹拌する。反応液を留去し、残渣に水を
加えて結晶化させる。過後エーテルで洗浄し乾
燥して化合物〔〕を得る。収量7.1ｇ（82％）。Reference example Synthesis of N-cyano-N',S-ethyleneisothiourea []: 10 g of dimethylcyanodithioimide carbonate
(0.0685 mol) and cysteamine hydrochloride 6.8 g
(0.0685 mol) and triethylamine 6.9 g
(0.0685 mol) was added to 100 ml of ethanol and heated to room temperature.
Stir for ~4 hours. The reaction solution is distilled off, and water is added to the residue for crystallization. After filtering, wash with ether and dry to obtain the compound []. Yield 7.1g (82%).
融点：155〜158℃。 Melting point: 155-158℃.
TLC：メルク・キーゼルゲル60F254アルミニウ
ム板（層厚0.2mm）を使用し、酢酸エチルで展開
すると、Rf＝0.5（2顕色）。 TLC: R f = 0.5 ( 2 developed) using Merck Kieselgel 60F 254 aluminum plate (layer thickness 0.2 mm) and developed with ethyl acetate.
赤外吸収スペクトル：第２図に示す。 Infrared absorption spectrum: Shown in Figure 2.
第１図は本発明目的化合物（化合物〔〕）の
赤外吸収スペクトル、第２図は原料化合物（化合
物〔〕）の赤外吸収スペクトルである。
FIG. 1 shows the infrared absorption spectrum of the object compound of the present invention (compound []), and FIG. 2 shows the infrared absorption spectrum of the raw material compound (compound []).
Claims (1)
レアとメチルアミンを反応させて、Ｎ−シアノ−
N′−メチル−N″−（２−メルカプトエチル）グア
ニジンを得ることを特徴とするグアニジン誘導体
の製造方法。1 React N-cyano-N',S-ethyleneisothiourea and methylamine to form N-cyano-
A method for producing a guanidine derivative, which comprises obtaining N'-methyl-N''-(2-mercaptoethyl)guanidine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7109782A JPS58188855A (en) | 1982-04-27 | 1982-04-27 | Preparation of guanidine derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7109782A JPS58188855A (en) | 1982-04-27 | 1982-04-27 | Preparation of guanidine derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58188855A JPS58188855A (en) | 1983-11-04 |
| JPH0328421B2 true JPH0328421B2 (en) | 1991-04-19 |
Family
ID=13450689
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7109782A Granted JPS58188855A (en) | 1982-04-27 | 1982-04-27 | Preparation of guanidine derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58188855A (en) |
-
1982
- 1982-04-27 JP JP7109782A patent/JPS58188855A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS58188855A (en) | 1983-11-04 |
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