JPH03251573A - Production of cimetidine - Google Patents
Production of cimetidineInfo
- Publication number
- JPH03251573A JPH03251573A JP2042389A JP4238990A JPH03251573A JP H03251573 A JPH03251573 A JP H03251573A JP 2042389 A JP2042389 A JP 2042389A JP 4238990 A JP4238990 A JP 4238990A JP H03251573 A JPH03251573 A JP H03251573A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- methyl
- cimetidine
- guanidine
- compound
- 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
- 229960001380 cimetidine Drugs 0.000 title claims abstract description 12
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- -1 alkali metal alkoxide Chemical class 0.000 claims abstract description 12
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 6
- 150000002357 guanidines Chemical class 0.000 claims abstract description 5
- GCYDEHNKSNMNMN-UHFFFAOYSA-N (5-methyl-1h-imidazol-4-yl)methanethiol Chemical compound CC=1NC=NC=1CS GCYDEHNKSNMNMN-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000005905 mesyloxy group Chemical group 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 12
- 150000001875 compounds Chemical class 0.000 abstract description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 abstract description 6
- 239000012299 nitrogen atmosphere Substances 0.000 abstract description 3
- IWDXEQQPYYDWDM-UHFFFAOYSA-N 1-cyano-3-(2-hydroxyethyl)-2-methylguanidine Chemical compound N#CNC(=NC)NCCO IWDXEQQPYYDWDM-UHFFFAOYSA-N 0.000 abstract description 2
- 230000000767 anti-ulcer Effects 0.000 abstract description 2
- 238000001816 cooling Methods 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- AQIXAKUUQRKLND-UHFFFAOYSA-N cimetidine Chemical compound N#C/N=C(/NC)NCCSCC=1N=CNC=1C AQIXAKUUQRKLND-UHFFFAOYSA-N 0.000 abstract 1
- 150000002460 imidazoles Chemical class 0.000 abstract 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 abstract 1
- 238000000034 method Methods 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- AXJZCJSXNZZMDU-UHFFFAOYSA-N (5-methyl-1h-imidazol-4-yl)methanol Chemical compound CC=1N=CNC=1CO AXJZCJSXNZZMDU-UHFFFAOYSA-N 0.000 description 1
- XNPSFFSMEXSPKL-UHFFFAOYSA-N 2-(2-methoxyethyl)guanidine Chemical compound COCCN=C(N)N XNPSFFSMEXSPKL-UHFFFAOYSA-N 0.000 description 1
- PDWPOXKSTFGRIT-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-1h-imidazole;hydrochloride Chemical compound Cl.CC=1NC=NC=1CCl PDWPOXKSTFGRIT-UHFFFAOYSA-N 0.000 description 1
- 102000003710 Histamine H2 Receptors Human genes 0.000 description 1
- 108090000050 Histamine H2 Receptors Proteins 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- IULFXBLVJIPESI-UHFFFAOYSA-N bis(methylsulfanyl)methylidenecyanamide Chemical compound CSC(SC)=NC#N IULFXBLVJIPESI-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical class [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- KKVTYAVXTDIPAP-UHFFFAOYSA-M sodium;methanesulfonate Chemical compound [Na+].CS([O-])(=O)=O KKVTYAVXTDIPAP-UHFFFAOYSA-M 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、イミダゾール系化合物の製造方法に関し、さ
らに詳しくは、次の式
（）
（式中、Ｙはトシルオキシ又はメシルオキシ基を示す）
で表わされるＮ−シアノ−Ｎ゛−メチル−Ｎ”−［２［
（４−メチル−５−イミダゾリル）−メチルチオ］−エ
チル］グアニジン（一般名：シメチジン）の製造方法に
関する。[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for producing an imidazole compound, and more specifically, it is represented by the following formula () (wherein Y represents a tosyloxy or mesyloxy group). N-cyano-N゛-methyl-N''-[2[
The present invention relates to a method for producing (4-methyl-5-imidazolyl)-methylthio]-ethyl]guanidine (common name: cimetidine).
［従来の技術］
シメチジンは、ヒスタミンＨ２受容体遮断作用を有する
化合物として知られており、臨床的には、抗潰瘍治療剤
として広く用いられている。[Prior Art] Cimetidine is known as a compound having a histamine H2 receptor blocking effect, and is widely used clinically as an anti-ulcer therapeutic agent.
従来よりシメチジンを製造する方法は数多く知られてお
り、その例としては、特開昭４９−７５５７４号、同５
１−５４５６１号、同５１−５４５６２号等に記載の方
法が挙げられる。Many methods for producing cimetidine have been known, examples of which include JP-A Nos. 49-75574 and 5.
Examples include methods described in No. 1-54561 and No. 51-54562.
［発明が解決しようとする課題］
しかし、これらの公知方法は、反応経路が多く、反応条
件が複雑であったり、反応に際し、高価な試薬を用いる
必要があるなど経済的に不利であり、工業上適当とはい
えなかった。[Problems to be Solved by the Invention] However, these known methods are economically disadvantageous, such as having many reaction routes, complicated reaction conditions, and the need to use expensive reagents during the reaction. It just wasn't appropriate.
従って、更に改良されたシメチジンの製造方法の提供が
求められていた。Therefore, it has been desired to provide a further improved method for producing cimetidine.
［課題を解決するための手段］
本発明者等は、上記の欠点を解決すべく種々研究を重ね
た結果、次に述べるような経済性に優れた新しい方法を
見出し、本発明を完成した。[Means for Solving the Problems] As a result of various studies to solve the above-mentioned drawbacks, the present inventors have discovered a new method with excellent economic efficiency as described below, and have completed the present invention.
すなわち、本発明は次の式（Ｉ）
（Ｉ）
で表わされる４−メチル−５−メルカプトメチルイミダ
ゾール又はその塩と、式（ＩＩ）（ＩＩ ）
（式中、Ｙはトシルオキシ又はメシルオキシ基を示す）
で表わされるグアニジン誘導体をアルカリ金属アルコキ
サイドの存在下反応させることを特徴とする式（ｍ）
（ｍ）
で表わされるシメチジンの製造方法を提供するものであ
る。That is, the present invention relates to 4-methyl-5-mercaptomethylimidazole or a salt thereof represented by the following formula (I) (I) and the formula (II) (II) (wherein, Y represents a tosyloxy or mesyloxy group) The present invention provides a method for producing cimetidine represented by formula (m) (m), which comprises reacting a guanidine derivative represented by formula (m) in the presence of an alkali metal alkoxide.
本発明方法の出発原料である４−メチル−５−メルカプ
トメチルイミダゾール（Ｉ）は、すでに公知の化合物で
あり、また、その塩は、化合物（Ｉ）に常法により塩酸
、硫酸等の酸を作用させることにより得ることができる
。4-Methyl-5-mercaptomethylimidazole (I), which is the starting material for the method of the present invention, is already a known compound, and its salt can be obtained by adding an acid such as hydrochloric acid or sulfuric acid to compound (I) in a conventional manner. It can be obtained by making it act.
他の出発原料であるグアニジン誘導体（ＩＩ）は、Ｎ−
シアノ−Ｎ゛−メチル−Ｎ″−（２−ヒドロキシエチル
）グアニジンに公知の方法によりメシルハライド又はト
シルハライドを作用させることにより調製される。Another starting material, guanidine derivative (II), is N-
It is prepared by reacting cyano-N''-methyl-N''-(2-hydroxyethyl)guanidine with mesyl halide or tosyl halide by a known method.
また、反応に用いられるアルカリ金属アルコキサイドと
しては、ナトリウムメトキサイド、ナトリウムエトキサ
イド、カリウムメトキサイド、カリウムエトキサイド、
等が例示される。In addition, the alkali metal alkoxides used in the reaction include sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide,
etc. are exemplified.
本発明方法を実施するには、化合物（Ｉ）、化合物（Ｉ
Ｉ ）及びアルカリ金属アルコキサイドを、メタノール
等の有機溶媒中、窒素零囲気下、冷却しながら数時間混
合撹拌すれば良い。To carry out the method of the present invention, compound (I), compound (I)
I) and an alkali metal alkoxide may be mixed and stirred for several hours while cooling in an organic solvent such as methanol under a nitrogen atmosphere.
叙上の如くして得られたシメチジンは、必要に応じ、カ
ラムクロマトグラフィー、再結晶等公知の精製手段によ
り更に精製することもできる。Cimetidine obtained as described above can be further purified by known purification means such as column chromatography and recrystallization, if necessary.
［発明の効果］
本発明方法によれば、シメチジンを容易に好収率で得る
ことができる。[Effects of the Invention] According to the method of the present invention, cimetidine can be easily obtained in good yield.
［実施例］ 次に実施例を挙げ本発明を更に詳しく説明する。[Example] Next, the present invention will be explained in more detail with reference to Examples.
実施例 １゜
（１）４−メチル−５−ヒドロキシメチル−イミダゾー
ル ２７．２ ｇを室温下、撹拌しながら塩化チオニル
５２ｍ１中へ加える。Example 1°(1) 27.2 g of 4-methyl-5-hydroxymethyl-imidazole are added to 52 ml of thionyl chloride at room temperature with stirring.
加え紡わった後、水浴中で３０分間加温し、ついで減圧
下、溶媒留去し、残留物をエタノール−ジエチルエーテ
ルより再結晶し、融点２２２〜２２５°Ｃの無色結晶と
して、４−メチル−５−クロロメチルイミダゾール塩酸
塩２５．０ｇを得る。After addition and spinning, it was heated in a water bath for 30 minutes, then the solvent was distilled off under reduced pressure, and the residue was recrystallized from ethanol-diethyl ether to give 4-methyl as colorless crystals with a melting point of 222-225°C. 25.0 g of -5-chloromethylimidazole hydrochloride is obtained.
（２）（１）て得られた４−メチル−５−クロロメチル
イミダゾール塩酸塩 １６．６ｇおよびチオ尿素９．１
ｇをアセトン１０１００Ｏ中で６時間加熱還流後、溶媒
留去し、次いで炭酸カリウム飽和水溶液５００ｍ１を加
え、７０°Ｃで３０分間撹拌した。この後、溶媒留去し
、２−プロパツール１０１００Ｏを加え、塩化水素を通
送してｐＨ１とした後、不溶物を濾過し、濾渣を濃縮し
、残漬を２−プロパノ−ルーエーテル（１：４）より再
結晶し、融点 ２３０〜２３２℃の４−メチル−５−チ
オメチルイミダゾール塩酸塩
１１．６ｇを得る。(2) 16.6 g of 4-methyl-5-chloromethylimidazole hydrochloride obtained in (1) and 9.1 g of thiourea
After heating and refluxing g in acetone (10,100 O) for 6 hours, the solvent was distilled off, and then 500 ml of a saturated potassium carbonate aqueous solution was added, followed by stirring at 70°C for 30 minutes. Thereafter, the solvent was distilled off, 2-propanol ether (10100O) was added, and hydrogen chloride was passed through to adjust the pH to 1. :4) to obtain 11.6 g of 4-methyl-5-thiomethylimidazole hydrochloride having a melting point of 230 to 232°C.
（３）ジメチル−Ｎ−シアノジチオイミノカルボネート
１５．４ｇをエタノール２００ｍ１に溶解し、０℃に
てエタノールアミン６．１ｇを加え、３０分間撹拌後、
室温にて５時間反応させる。さらに３０％メチルアミン
のエタノール溶液 １５．５ ｇを滴下し、室温にて約
１２Ｒ間撹拌後、減圧下、溶媒留去し、残留物を酢酸エ
チルより再結晶し、融点 １１０〜１１２℃のＮ−メチ
ル−Ｎ′シアノ−Ｎ”−（２−ヒドロキシエチル）グア
ニジン１１．３ｇを得る。(3) 15.4 g of dimethyl-N-cyanodithioiminocarbonate was dissolved in 200 ml of ethanol, 6.1 g of ethanolamine was added at 0°C, and after stirring for 30 minutes,
React for 5 hours at room temperature. Furthermore, 15.5 g of a 30% ethanol solution of methylamine was added dropwise, and after stirring at room temperature for about 12 R, the solvent was distilled off under reduced pressure, and the residue was recrystallized from ethyl acetate. 11.3 g of -methyl-N'cyano-N''-(2-hydroxyethyl)guanidine are obtained.
（４）Ｎ−メチル−Ｎ′−シアノ−Ｎ”（２−ヒドロキ
シエチル）グアニジン ７．１ｇをジクロルメタン１０
０ｍ１ｌ：懸濁し、トリエチルアミン ６．０ｇを加え
、次いて室温にてメシルクロライド ５．７ｇを徐々に
滴下した。２時間反応後、不溶物を濾過し、濾液を濃縮
したのち、残漬をジクロルメタンより再結晶し、融点１
８８〜１９０″Ｃの無色結晶としてＮ−メチル−Ｎ“−
シアノ−Ｎ ＩＩ（２−メチルオキシエチル）グアニジ
ン７．４ｇを得る。(4) 7.1 g of N-methyl-N'-cyano-N" (2-hydroxyethyl) guanidine was added to 10 g of dichloromethane.
0 ml: Suspended, 6.0 g of triethylamine was added, and then 5.7 g of mesyl chloride was gradually added dropwise at room temperature. After 2 hours of reaction, the insoluble matter was filtered, the filtrate was concentrated, and the residue was recrystallized from dichloromethane to give a melting point of 1.
N-methyl-N"- as colorless crystals of 88-190"C
7.4 g of cyano-N II (2-methyloxyethyl)guanidine are obtained.
（５）窒累零囲気下、撹拌しながら、４−メチル−５−
チオメチルイミダゾール塩酸塩１６ｇのメタノール５０
０ｍ１スラリーに、−５〜０°Ｃにてナトリウムメトキ
サイドの３０％メタノール性溶液１８ｍｌを滴下し、次
いて、Ｎ−メチル−Ｎ゛−シアノ−Ｎ′（２−メチルオ
キシエチル）グアニジン２２ｇを少しずつ加え、その後
、１時間を要してナトリウムメトキサイド３ｏ％メタノ
ール性溶濠を１８ｍ１滴下した。さらに、１時間撹拌後
、分離したナトリウムメシレートおよび塩化ナトリウム
をろ別し、メタノール５０ｍ１で２回洗浄し、合したろ
液を蒸発乾固した。残留した粗製のシメチジンを２−プ
ロパツールで再結晶し精製シメチジン１６．４ｇを得る
。(5) Under a zero nitrogen atmosphere, while stirring, 4-methyl-5-
Thiomethylimidazole hydrochloride 16g methanol 50
18 ml of a 30% methanolic solution of sodium methoxide was added dropwise to the 0 ml slurry at -5 to 0°C, followed by 22 g of N-methyl-N'-cyano-N'(2-methyloxyethyl)guanidine. It was added little by little, and then 18 ml of 30% methanol sodium methoxide was added dropwise over a period of 1 hour. After further stirring for 1 hour, the separated sodium mesylate and sodium chloride were filtered off, washed twice with 50 ml of methanol, and the combined filtrate was evaporated to dryness. The remaining crude cimetidine was recrystallized with 2-propanol to obtain 16.4 g of purified cimetidine.
以 上Below Up
Claims (1)
ゾール又はその塩と、 式（II）▲数式、化学式、表等があります▼（II） （式中、Ｙはトシルオキシ又はメシルオキシ基を示す） で表わされるグアニジン誘導体をアルカリ金属アルコキ
サイドの存在下反応させることを特徴とする式（III） ▲数式、化学式、表等があります▼（III） で表わされるシメチジンの製造方法。(1) 4-methyl-5-mercaptomethylimidazole or its salt represented by the following formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) and formula (II) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (II) (In the formula, Y represents a tosyloxy or mesyloxy group) Formula (III) characterized by reacting a guanidine derivative represented by the following in the presence of an alkali metal alkoxide ▲ Numerical formula, chemical formula, table, etc. There is a method for producing cimetidine represented by ▼ (III).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2042389A JPH03251573A (en) | 1990-02-26 | 1990-02-26 | Production of cimetidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2042389A JPH03251573A (en) | 1990-02-26 | 1990-02-26 | Production of cimetidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03251573A true JPH03251573A (en) | 1991-11-11 |
Family
ID=12634713
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2042389A Pending JPH03251573A (en) | 1990-02-26 | 1990-02-26 | Production of cimetidine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03251573A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113234018A (en) * | 2021-05-11 | 2021-08-10 | 石家庄市普力制药有限公司 | Production method of cimetidine |
-
1990
- 1990-02-26 JP JP2042389A patent/JPH03251573A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113234018A (en) * | 2021-05-11 | 2021-08-10 | 石家庄市普力制药有限公司 | Production method of cimetidine |
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