JPS5821913B2 - 5 (4) - Aminoimidazole - 4 (5) - Carboxyamidonoseiho - Google Patents
5 (4) - Aminoimidazole - 4 (5) - CarboxyamidonoseihoInfo
- Publication number
- JPS5821913B2 JPS5821913B2 JP49136868A JP13686874A JPS5821913B2 JP S5821913 B2 JPS5821913 B2 JP S5821913B2 JP 49136868 A JP49136868 A JP 49136868A JP 13686874 A JP13686874 A JP 13686874A JP S5821913 B2 JPS5821913 B2 JP S5821913B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- aminoimidazole
- hydrochloride
- yield
- temperature
- 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
- 238000000034 method Methods 0.000 claims description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 8
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 7
- 239000012535 impurity Substances 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 5
- -1 alkyl ketone Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 238000000746 purification Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 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 5
- 239000013078 crystal Substances 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 125000005233 alkylalcohol group Chemical group 0.000 description 2
- 238000004040 coloring Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- DPZSNGJNFHWQDC-ARJAWSKDSA-N (z)-2,3-diaminobut-2-enedinitrile Chemical compound N#CC(/N)=C(/N)C#N DPZSNGJNFHWQDC-ARJAWSKDSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000001479 atomic absorption spectroscopy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Description
【発明の詳細な説明】
本発明は、アルカリ金属無機塩を不純物として含有する
５（４）−アミノイミダゾール−４（５）−カルボキシ
アミド（以下、化合物Ｉと略記する）を５（４）−アミ
ノイミダゾール−４（５）−カルボキシアミド塩酸塩と
して分離精製する方法に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention provides 5(4)-aminoimidazole-4(5)-carboxamide (hereinafter abbreviated as compound I) containing an alkali metal inorganic salt as an impurity. The present invention relates to a method for separating and purifying aminoimidazole-4(5)-carboxamide hydrochloride.
化合物■は核酸前駆物質、調味料、２−アルキルヒポキ
サンチン、ヒポキサンチン、グアニン、その地条（のプ
リン誘導体の合成中間体として、更に医薬、農薬等の分
野に用途を有する各種イミダゾール誘導体の合成中間体
として重要な化合物である。Compound ■ can be used as a synthetic intermediate for nucleic acid precursors, seasonings, 2-alkylhypoxanthine, hypoxanthine, guanine, and purine derivatives thereof, and also for the synthesis of various imidazole derivatives that have applications in the fields of medicine, agricultural chemicals, etc. It is an important compound as an intermediate.
従って化合物■を効率よ（分離精製することは工業上、
極めて有益なことである。Therefore, it is industrially difficult to efficiently separate and purify compound ■.
This is extremely beneficial.
従来、化合物■の分離精製法として多数の方法が報告さ
れている。A large number of methods have been reported to date for the separation and purification of compound (1).
例えば、Ｃｈｅ ｍ ｉ ５ｃｈｅＢｅｒｉｃｈｔｅ
５６巻、６８３頁（１９２３年）によるピクラートとし
て分離する方法、Ｊｏｕｒｒａｌ ｏｆＯｒｇａｎｉｃ
Ｃｈｅｍｉｓｔｒｙ ２４巻、２５６〜７頁（１９５
９年）による全体を蒸発乾固して、水、エタノール、エ
ーテルで再結晶する方法、５ｃｉｅｎｃｅ１１２巻、６
５４頁（１９５０年）による硝酸銀とアンモニアで沈殿
させる方法、特公昭４２−６９１１号による強酸性カチ
オン交換樹脂の吸着による方法、特公昭４２−６９０９
号による金属錯塩として分離する方法等がある。For example, Che m i 5che Berichte
56, p. 683 (1923), Journal of Organic
Chemistry Vol. 24, pp. 256-7 (195
9) method of evaporating the entire product to dryness and recrystallizing it with water, ethanol, and ether, 5science Vol. 112, 6
Method of precipitation with silver nitrate and ammonia according to p. 54 (1950), Method of adsorption with strongly acidic cation exchange resin according to Japanese Patent Publication No. 42-6911, Japanese Patent Publication No. 42-6909
There are methods to separate it as a metal complex salt according to the No.
また、これらの基本形を改良した多数の分離精製法が公
知である。In addition, many separation and purification methods are known that improve upon these basic forms.
しかし、これらの方法はいずれも操作が繁雑であるか、
大量処理の場合に危険を伴うか、分離剤が高価であるか
、又は精製率が低い等のため、化合物Ｉの工業的な精製
法としては種々の欠点を有しており、満足し得るものと
はいい難い。However, all of these methods are complicated to operate, or
This method is not satisfactory as an industrial purification method for Compound I, as it has various drawbacks, such as being dangerous in large-scale processing, expensive separation agents, and low purification efficiency. That's hard to say.
本発明者等は、先に化合物■の製造法としてジアミノマ
レオニトリルより得られる４（５）−シアノイミダゾー
ル−５（４）−カルバミン酸エステルヲアルカリ加水分
解して容易に、しかも好収率で化合物■が得られる合成
方法を開発し、特許出願（特願昭４８−７９０９７号）
した。As a method for producing compound (1), the present inventors first carried out alkaline hydrolysis of 4(5)-cyanoimidazole-5(4)-carbamic acid ester obtained from diaminomaleonitrile to easily and in a good yield. Developed a synthetic method to obtain compound ■ and filed a patent application (Japanese Patent Application No. 79097/1982)
did.
本合成法の如き加水分解により化合物Ｉを合成する場合
、反応終了液を無機酸等で中和するため得られる粗化合
物Ｉには塩化ナトリウム、硫酸ナトリウム等のアルカリ
金属からなる無機塩を不純物として含有しており、その
精製が繁雑である。When compound I is synthesized by hydrolysis as in this synthesis method, the reaction finished liquid is neutralized with an inorganic acid, etc., so that the resulting crude compound I contains an inorganic salt of an alkali metal such as sodium chloride or sodium sulfate as an impurity. The purification process is complicated.
゛本発明者らは、アルカリ金属無機塩を不純物
として含有する化合物■の工業的に有利な精製法につい
て種り研究、検討を重ねた結果、粗化合物Ｉから化合物
■を有機溶媒で抽出し、抽出液に塩化水素を導入するこ
とにより、化合物■が塩酸塩として容易に、しかも高純
度、好収率で分離精製されて得られることを見出し、本
発明方法を完成するに至った。゛As a result of extensive research and study on an industrially advantageous purification method for compound (1) containing an alkali metal inorganic salt as an impurity, the present inventors extracted compound (2) from crude compound I with an organic solvent, The present inventors have discovered that by introducing hydrogen chloride into the extract, Compound (1) can be easily separated and purified as a hydrochloride salt with high purity and good yield, and have completed the method of the present invention.
本発明方法によるときは、無機塩を含有する化合物■が
容易に精製され高純度の化合物Ｉが塩酸塩として好収率
で得られるので化合物■の工業的精製法として極めて有
利な方法である。When the method of the present invention is used, Compound (1) containing an inorganic salt can be easily purified and highly purified Compound (1) can be obtained as a hydrochloride in a good yield, so it is an extremely advantageous method as an industrial purification method for Compound (1).
本発明方法における精製の対象である粗化合物■中の不
純物はアルカリ金属からなる無機塩、即ち塩化物、硫酸
塩等である。The impurities in the crude compound (1), which is the object of purification in the method of the present invention, are inorganic salts of alkali metals, such as chlorides and sulfates.
該無機塩の種類は化合物■の製造法及びその処理法によ
り異なるが、一般には塩化ナトリウムである。The type of inorganic salt varies depending on the method for producing compound (1) and its processing method, but is generally sodium chloride.
本発明で使用される抽出溶媒は化合物■と反応性のない
有機溶媒であるが、低級アルキルアルコール、低級アル
キルケトンが好ましい。The extraction solvent used in the present invention is an organic solvent that has no reactivity with compound (1), and lower alkyl alcohols and lower alkyl ketones are preferred.
低級アルキルアルコール類としてはメチルアルコール、
エチルアルコール、ｎ−プロピルアルコール、インプロ
ピルアルコール、ｎ−ブチルアルコール等カ挙げられ、
また、低級アルキルケトン類としては、アセトン、メチ
ルエチルケトン、メチルイソブチルケトン等が挙げられ
る。Examples of lower alkyl alcohols include methyl alcohol,
Examples include ethyl alcohol, n-propyl alcohol, inpropyl alcohol, n-butyl alcohol, etc.
Furthermore, examples of lower alkyl ketones include acetone, methyl ethyl ketone, methyl isobutyl ketone, and the like.
抽出溶媒の使用量は、化合物と無機塩との比率、抽出方
法、処理温度、溶媒の種類によって異なり一定でないが
、塩化ナトリウム等の不純物を含有する化合物■を溶媒
に溶解し、不溶の不純分を１過する方法による場合は、
溶媒の使用量は化合物■に対して５〜７０重量倍、好ま
しくは１０〜５０重量倍である。The amount of extraction solvent used varies depending on the ratio of compound and inorganic salt, extraction method, processing temperature, and type of solvent, but it is not fixed. If the method is to pass the
The amount of the solvent to be used is 5 to 70 times, preferably 10 to 50 times the weight of Compound (1).
５重量倍より少くてもよいが、少（なるにつれて収率が
低下する。It may be less than 5 times the weight, but the yield decreases as it becomes smaller.
７０重量倍以上でも問題はないが、余り大量の使用はい
たずらに装置を大きくし、また後処理に長時間を要する
等のため、経済的に好ましくない。Although there is no problem if the amount is 70 times the weight or more, the use of too large a quantity is economically undesirable because it unnecessarily increases the size of the equipment and requires a long time for post-processing.
従って、使用量はこれらの諸要因を考慮し、最も有利な
条件に決定すべきである。Therefore, the amount to be used should be determined in consideration of these factors and under the most advantageous conditions.
処理温度、即ち抽出時及び塩化水素の導入による化合物
■の析出時の温度は溶媒の種類、使用量等により左右さ
れ一定でないが、通常１０〜１００℃、好ましくは２０
〜８０℃である。The processing temperature, that is, the temperature at the time of extraction and the precipitation of compound
~80°C.
化合物■の析出時には２０〜４０℃程度に冷却するのが
更に好ましい。It is more preferable to cool the mixture to about 20 to 40°C during precipitation of compound (1).
８０℃以上でもよいが余り温度が高いと処理液が着色し
たり、収率低下の原因となり、また不必要に塩化ナトリ
ウム等の無機塩の溶解度を高める等の危険があるため、
これらの諸条件を考慮し、最も有効な条件を選択すべき
である。The temperature may be 80°C or higher, but if the temperature is too high, it may cause coloring of the processing solution, decrease in yield, and there is a risk of unnecessarily increasing the solubility of inorganic salts such as sodium chloride.
Considering these conditions, the most effective conditions should be selected.
塩化水素は乾燥ガスの使用が望ましい。It is preferable to use dry gas for hydrogen chloride.
未乾燥ガスを使用してもよいが水分が多くなるにつれて
収率が低下する恐れがあり好ましくない。Although undried gas may be used, it is not preferable because the yield may decrease as the moisture content increases.
また、塩化水素の導入速度と温度は相対的関係にあり、
導入速度が余り遅いと長時間を要し、また余り速いと温
度が上昇し副反応を併発したり、着色の原因となったり
する等のため、これ等の諸要因を考慮し最も適当な導入
速度と温度を決定すべきである。In addition, there is a relative relationship between the introduction rate and temperature of hydrogen chloride.
If the introduction speed is too slow, it will take a long time, and if it is too fast, the temperature will rise, causing side reactions or coloring, so consider these factors and choose the most appropriate introduction method. The speed and temperature should be determined.
導入する塩化水素の量は溶媒の種類、量により異なるが
、通常化合物■に対して１〜１０重量倍、好ましくは１
〜７重量倍である。The amount of hydrogen chloride to be introduced varies depending on the type and amount of the solvent, but is usually 1 to 10 times the weight of compound (1), preferably 1
~7 times the weight.
１０重量倍よし多くてもよいが余り過剰に導入すると、
副反応を併発したり１着色の原因となるので、化合物■
の塩酸塩が析出しなくなった時点で塩化水素の導入を停
止することが好ましい。It may be 10 times the weight or more, but if you introduce too much,
Do not use compounds ■ as they may cause side reactions or cause discoloration.
It is preferable to stop the introduction of hydrogen chloride when the hydrochloride no longer precipitates.
； 以上の諸条件を適当に組み合せることにより容易に
好収率で化合物Ｉを塩酸塩として得ることができるが、
更に高純度品が要求される場合は、塩化水素の導入前に
、化合物■の溶解した処理液を活性炭で処理するか、又
は、得られた化合物■の１塩酸塩を熱水より活性炭を用
いて再結晶すればよい。; Compound I can be easily obtained as a hydrochloride in good yield by appropriately combining the above conditions; however,
If a product with even higher purity is required, before introducing hydrogen chloride, the treatment liquid in which compound It can be recrystallized.
なお、化合物■に含まれている不純物が塩化ナトリウム
の場合、本発明方法によって得られた化合物■塩酸塩中
のナトリウム含率は次の通りであった。In addition, when the impurity contained in compound (1) was sodium chloride, the sodium content in the compound (1) hydrochloride obtained by the method of the present invention was as follows.
以下、実施例を挙げて本発明方法を更に詳細に説明する
。Hereinafter, the method of the present invention will be explained in more detail with reference to Examples.
実施例 Ｉ
４（５）−シアノイミダゾール−５（４）−カルバミン
酸メチルエステル１６．６グを力性ソーダ１６グと水１
５０ｍ１で加水分解し、塩酸で中和後減圧乾固して得た
塩化ナトリウム２３．４ｆを含む粗化合物１３６１にエ
タノール３００ｍＡを加え水浴を用いて３５〜４０℃で
１０分間攪拌溶解した。Example I 16.6 g of 4(5)-cyanoimidazole-5(4)-carbamic acid methyl ester was mixed with 16 g of sodium hydroxide and 1 portion of water.
To the crude compound 1361 containing 23.4f of sodium chloride obtained by hydrolysis with 50ml of hydrochloric acid, neutralization with hydrochloric acid, and drying under reduced pressure, 300mA of ethanol was added, and the mixture was stirred and dissolved at 35 to 40°C for 10 minutes using a water bath.
同温度で１過して塩化ナトリウムを１過し、１液を常温
まで冷却し、塩化水素５０グを２５〜３０℃で１０分間
かげて導入した。The solution was filtered once at the same temperature, and sodium chloride was passed through it once. The first solution was cooled to room temperature, and 50 g of hydrogen chloride was introduced at 25 to 30° C. for 10 minutes.
析出した沈殿を１集し。エタノール２０ｍ１で洗浄後７
５〜８５℃で６時間乾燥して５（４）−アミノイミダゾ
ール−４（５）−カルボキシアミド塩酸塩の結晶１５．
５ｆを得た。Collect the precipitate that has separated out. After washing with 20ml of ethanol7
Dry at 5-85°C for 6 hours to obtain crystals of 5(4)-aminoimidazole-4(5)-carboxamide hydrochloride 15.
I got 5f.
収率９５．４％、融点２５５〜２５６℃を示した。It showed a yield of 95.4% and a melting point of 255-256°C.
製品中のナトリウム含率を原子吸光分析で測定したとこ
ろ０．０２％であった。The sodium content in the product was measured by atomic absorption spectrometry and was found to be 0.02%.
また得られた白色結晶の紫外吸収スペクトル、赤外吸収
スペクトル元素分析値は標準品と完全に一致した。Furthermore, the ultraviolet absorption spectrum and infrared absorption spectrum elemental analysis values of the obtained white crystals completely matched those of the standard product.
実施例 ２
イソプロピルアルコール５００ｍ１を用い、５０〜５５
℃で溶解する以外は実施例１と同様に処理し、化合物Ｉ
塩酸塩の結晶１５．３Ｐを得た。Example 2 Using 500ml of isopropyl alcohol, 50-55
Compound I was treated in the same manner as in Example 1 except that it was dissolved at ℃
15.3P of hydrochloride crystals were obtained.
収率９４．２％、融点２５５〜２５６℃、製品中のナト
リウム含率は０．０１％であった。The yield was 94.2%, the melting point was 255-256°C, and the sodium content in the product was 0.01%.
実施例 ３
エタノール１５０７７１１１イソプロピルアルコール１
５０ｍ１を用いる以外、実施例１と同様に処理し化合物
■塩酸塩の結晶１５．４ｆを得た。Example 3 Ethanol 15077111 Isopropyl alcohol 1
The process was carried out in the same manner as in Example 1, except that 50 ml of the compound was used to obtain 15.4 f of crystals of compound (1) hydrochloride.
収率９４．７％、融点２５５〜２５６℃であった。The yield was 94.7%, and the melting point was 255-256°C.
製品中のナトリウム含率は０．０３％であった。The sodium content in the product was 0.03%.
実施例 ４
メチルエチルケトン８００ｍＡ！を用い５５〜６０、℃
で溶解する以外は実施例１と同様に処理し、化合物■塩
酸塩の結晶１５．６ｆを得た。Example 4 Methyl ethyl ketone 800mA! using 55-60℃
The treatment was carried out in the same manner as in Example 1 except that the compound was dissolved in 15.6f of crystals of compound (1) hydrochloride.
収率９６％、製品中のナトリウム含率は０．００９％で
あった。The yield was 96%, and the sodium content in the product was 0.009%.
Claims (1)
キシアミドを低級アルキルアルカノール及び又は低級ア
ルキルケトンで抽出後、該抽出液に塩化水素を導入する
ことを特徴とする不純物としてアルカリ金属無機塩を含
有する５（４）−アミノイミダゾール−４（５）−カル
ボキシアミドの精製法。1 After extracting 5(4)-aminoimidazole-4(5)-carboxamide with a lower alkyl alkanol and/or lower alkyl ketone, hydrogen chloride is introduced into the extract, and an alkali metal inorganic salt is added as an impurity. A method for purifying 5(4)-aminoimidazole-4(5)-carboxamide containing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49136868A JPS5821913B2 (en) | 1974-11-28 | 1974-11-28 | 5 (4) - Aminoimidazole - 4 (5) - Carboxyamidonoseiho |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49136868A JPS5821913B2 (en) | 1974-11-28 | 1974-11-28 | 5 (4) - Aminoimidazole - 4 (5) - Carboxyamidonoseiho |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5163173A JPS5163173A (en) | 1976-06-01 |
| JPS5821913B2 true JPS5821913B2 (en) | 1983-05-04 |
Family
ID=15185390
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP49136868A Expired JPS5821913B2 (en) | 1974-11-28 | 1974-11-28 | 5 (4) - Aminoimidazole - 4 (5) - Carboxyamidonoseiho |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5821913B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107325053A (en) * | 2017-08-15 | 2017-11-07 | 广东华南药业集团有限公司 | A kind of refined and discoloration method of Orazamide |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS49116063A (en) * | 1973-03-13 | 1974-11-06 |
-
1974
- 1974-11-28 JP JP49136868A patent/JPS5821913B2/en not_active Expired
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS49116063A (en) * | 1973-03-13 | 1974-11-06 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5163173A (en) | 1976-06-01 |
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