JPS58188860A - Preparation of imidazole derivative - Google Patents
Preparation of imidazole derivativeInfo
- Publication number
- JPS58188860A JPS58188860A JP57071096A JP7109682A JPS58188860A JP S58188860 A JPS58188860 A JP S58188860A JP 57071096 A JP57071096 A JP 57071096A JP 7109682 A JP7109682 A JP 7109682A JP S58188860 A JPS58188860 A JP S58188860A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- compound
- alkali metal
- ethyleneimine
- basic conditions
- 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
- 150000002460 imidazoles Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims abstract description 4
- 150000001340 alkali metals Chemical group 0.000 claims abstract description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000000615 nonconductor Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 9
- 238000006243 chemical reaction Methods 0.000 abstract description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 5
- 229910052783 alkali metal Inorganic materials 0.000 abstract description 5
- -1 alkali metal alkoxide Chemical class 0.000 abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 abstract description 3
- 102000003710 Histamine H2 Receptors Human genes 0.000 abstract description 2
- 108090000050 Histamine H2 Receptors Proteins 0.000 abstract description 2
- 229960001380 cimetidine Drugs 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 2
- JEOZNMMOIBLWLV-UHFFFAOYSA-N 2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethanamine Chemical compound CC=1N=CNC=1CSCCN JEOZNMMOIBLWLV-UHFFFAOYSA-N 0.000 abstract 1
- 239000005557 antagonist Substances 0.000 abstract 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application 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
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960003151 mercaptamine Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Abstract
Description
【発明の詳細な説明】
で示烙ｒする４−メチル−５−（（２−アミノエチル）
千オメチル］イミダゾールの製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION 4-methyl-5-((2-aminoethyl)
The present invention relates to a method for producing [1,000-omethyl]imidazole.
本発明目的化合物ＣＩ］は、薬理活性をイアする化合物
、例えばＨ２受容体に対するヒスタミン拮抗剤として知
られる［シメチジンＪ（Ｎ−シアノーＮ′一メチル−Ｎ
″−４２−（（５−メチル−４−イミダゾリル）メヂル
チオ）エチル〕グアニシン）の合成に有用な化合物であ
る。Compound CI of the present invention] is a compound with pharmacological activity, for example, known as a histamine antagonist for H2 receptors [cimetidine J (N-cyano N'-methyl-N
It is a compound useful in the synthesis of ``-42-((5-methyl-4-imidazolyl)medylthio)ethyl]guanisine).
本発明方法によれは、下式〔旧
〔式中、Ｍは水素原子またはアルカリ金属原子を表わす
〕
で示これる化合物と、エチレンイミノ〔川〕とを、ｋス
媒中、強塩基性条件下に反応させることにより、１−」
的とするイミクゾール誘導体［１］を得る。According to the method of the present invention, a compound represented by the following formula (former formula, in which M represents a hydrogen atom or an alkali metal atom) and ethyleneimino are mixed in a KS medium under strongly basic conditions. By reacting below, 1-"
The target imixole derivative [1] is obtained.
上記反応は、好ましくは窒素気流などの不活性雰囲気下
に行なわれる。The above reaction is preferably carried out under an inert atmosphere such as a nitrogen stream.
溶媒は、水または各種有機溶剤が用いられるが、有機溶
剤としては、原料反応試剤が可溶な極性溶媒、例えばメ
タノール、エタノール、アセトン、アセトニトリルなど
が好ましい。As the solvent, water or various organic solvents are used, and preferred examples of the organic solvent include polar solvents in which the raw reaction reagents can be dissolved, such as methanol, ethanol, acetone, and acetonitrile.
塩基性条件は、例えば水酸化すｌ−ＩＪウム、水酸化カ
リウム、水酸化カルシウムなどのアルカリ金属またはア
ルカリ土類金属の水酸化物、あるいはナトリウ′ムエト
キシド、カリウムエトキシドなどのアルカリ金属アルコ
キサイドなどによって与えられる。Basic conditions can be achieved using, for example, hydroxides of alkali metals or alkaline earth metals such as sulfur hydroxide, potassium hydroxide, and calcium hydroxide, or alkali metal alkoxides such as sodium ethoxide and potassium ethoxide. Given.
上記反応は常温常圧下に、短時間で完結させることがで
きる。また、生成した目的化合物［１３は容易に高純度
で単離することができ、その収率は格別に高く、理論収
率の８５〜９０％に達する。The above reaction can be completed in a short time at room temperature and pressure. Moreover, the produced target compound [13] can be easily isolated with high purity, and its yield is exceptionally high, reaching 85 to 90% of the theoretical yield.
イ
なお、従来にも、化合物〔旧を用いて目的化合物［１１
を製造する方法として、システアミノ（Ｈ５Ｃ）Ｉ２Ｃ
Ｈ２ＮＨ２）を用いる方法（英国特許第ｔ３３ｓ１６ｃ
＋＋ｊ） 、相聞移動触媒の存在１′：に２−ハロエチ
ルアミンと反応させる方法（特開昭５６−１２７３６１
’ｊｊ）が知られているが、これに使用されるシステア
ミンや相聞移動触媒は極めて高価であり、１だ反応の完
結に比較的長時間を要するはが、副反応物を伴うため、
目的生成物の単離精製が困難で、収率も低い。本発明方
法では、高価な反応試剤を必要とせす、安価に効率良く
目的化合物［Ｉ）を得ることができる。b) Conventionally, compound [old] is used to refer to target compound [11
As a method for producing cysteamino (H5C) I2C
H2NH2) (UK patent no. t33s16c)
++j) A method of reacting 1′: with 2-haloethylamine in the presence of a phase transfer catalyst (JP-A-56-127361
'jj) is known, but the cysteamine and phase transfer catalysts used for this are extremely expensive, and it takes a relatively long time to complete the single reaction, but it also involves side reactants.
It is difficult to isolate and purify the desired product, and the yield is low. In the method of the present invention, the target compound [I] can be obtained efficiently and at low cost, which does not require expensive reaction reagents.
次に本発明の実施例について説明する。Next, examples of the present invention will be described.
実施例
メタノール１００ｍｌに金属ナトリウム４６ｙ（０，２
モル）を溶かし、ついで５−メチル−４−チオメチルイ
ミクゾール塩酸塩１３．３ｐ（０，１モル）を加え、窒
素を通じる。室温で、メタノール１０ｍｆｆにエチレン
イミン４．３ｙ（０，１モル）を溶かした溶液を上記溶
液に徐々に滴下する。滴Ｆ終ｒ後、１時間撹拌し、び過
して溶媒を留去する。Example Metallic sodium 46y (0,2
mol), then 13.3 p (0.1 mol) of 5-methyl-4-thiomethylimikuzole hydrochloride are added and nitrogen is passed through. At room temperature, a solution of 4.3y (0.1 mol) of ethyleneimine in 10 mff of methanol is gradually added dropwise to the above solution. After the addition of the drops, the mixture was stirred for 1 hour, filtered, and the solvent was distilled off.
残１？ｉ ’ｆ： Ｉ Ｎ塩酸にてｐＨ４に調節し、再
び留去する。1 left? i'f: Adjust the pH to 4 with IN hydrochloric acid and evaporate again.
残１−１をエタノールから再結晶して、目的化合物であ
る４〜メチル−５−４（２−アミノエチル）チオメチル
クイミグゾール２塩酸塩を得る。収量２１．７ｙ（８９
％）。融点１８９〜１９１℃。The residue 1-1 is recrystallized from ethanol to obtain the target compound, 4-methyl-5-4(2-aminoethyl)thiomethylquimiguzole dihydrochloride. Yield 21.7y (89
%). Melting point: 189-191°C.
代理人 弁理士 宮崎 新八部Agent: Patent Attorney Shinhachibe Miyazaki
Claims (1)
〕 で示される化合物と、エチレンイミンとを、慇媒中、強
塩基性条件下に反応させて、４−メチル＝５−［（２−
アミノエチル）千オメチル］イミクゾールを得ることを
特徴とするイミダゾール１否導体の製造方法。[Claims] [In the formula, M represents a hydrogen atom or an alkali metal fragment r] A compound represented by the following is reacted with ethyleneimine in a medium under strongly basic conditions to form 4-methyl =5-[(2-
1. A method for producing imidazole 1 non-conductor, which comprises obtaining (aminoethyl)1,000methyl]imikuzole.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57071096A JPS58188860A (en) | 1982-04-27 | 1982-04-27 | Preparation of imidazole derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57071096A JPS58188860A (en) | 1982-04-27 | 1982-04-27 | Preparation of imidazole derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS58188860A true JPS58188860A (en) | 1983-11-04 |
Family
ID=13450658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57071096A Pending JPS58188860A (en) | 1982-04-27 | 1982-04-27 | Preparation of imidazole derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58188860A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56127361A (en) * | 1980-01-14 | 1981-10-06 | Lek Tovarna Farmacevtskih | Manufacture of imidazole derivative |
-
1982
- 1982-04-27 JP JP57071096A patent/JPS58188860A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56127361A (en) * | 1980-01-14 | 1981-10-06 | Lek Tovarna Farmacevtskih | Manufacture of imidazole derivative |
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