JPH0359905B2 - - Google Patents
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- Publication number
- JPH0359905B2 JPH0359905B2 JP20602282A JP20602282A JPH0359905B2 JP H0359905 B2 JPH0359905 B2 JP H0359905B2 JP 20602282 A JP20602282 A JP 20602282A JP 20602282 A JP20602282 A JP 20602282A JP H0359905 B2 JPH0359905 B2 JP H0359905B2
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- JP
- Japan
- Prior art keywords
- general formula
- formula
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- represented
- acid
- Prior art date
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- 239000002253 acid Substances 0.000 claims description 19
- -1 β-nicotinoylaminoethyl group Chemical group 0.000 claims description 15
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 12
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 11
- 235000010288 sodium nitrite Nutrition 0.000 claims description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 5
- 239000011707 mineral Substances 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 3
- 125000005219 aminonitrile group Chemical group 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- GSKDBLIBBOYOFU-UHFFFAOYSA-N oxadiazol-5-amine Chemical class NC1=CN=NO1 GSKDBLIBBOYOFU-UHFFFAOYSA-N 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- BKILPAYYYRJTPP-UHFFFAOYSA-M sodium;formaldehyde;hydrogen sulfite;hydrate Chemical compound O.[Na+].O=C.OS([O-])=O BKILPAYYYRJTPP-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 229940124345 antianginal agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- RTIXFTKDETURTM-UHFFFAOYSA-N n-(2-aminoethyl)pyridine-3-carboxamide Chemical compound NCCNC(=O)C1=CC=CN=C1 RTIXFTKDETURTM-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
Description
【発明の詳細な説明】
本発明は新規なシドノンイミン化合物又はその
酸付加塩及びこれらの製法に係る。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel sydnonimine compounds or acid addition salts thereof and methods for producing them.
本発明による新規なシドノンイミン化合物は一
般式
（式中R1はモルホピロリジノ、モルホピペリ
ジノ又はβ−ニコチノイルアミノエチル基を意味
し、R2は水素又はカルボエトキシ基を意味する）
にて示される。 The novel sydnonimine compounds according to the present invention have the general formula (In the formula, R 1 means morphopyrrolidino, morphopiperidino or β-nicotinoylaminoethyl group, and R 2 means hydrogen or carboethoxy group)
It is shown in
一般式にて示される本発明による化合物は血
管拡張作用を有しており、従つて血圧降下剤又は
抗狭心剤として有用である。 The compounds according to the invention of the general formula have vasodilatory action and are therefore useful as antihypertensive or antianginal agents.
本発明方法によれば、一般式にて示される化
合物及びその酸付加塩は、ホルムアルデヒド及び
シアン化合物を一般式
R1−NH2 （）
（式中R1はモルホピロリジノ、モルホピペリ
ジノ又はβ−ニコチノイルアミノエチル基を意味
する）にて示されるアミンと反応させ、得たる一
般式
R1−NH−CH2CN （）
（式中R1は前記の意味を有する）にて示され
るアミノニトリルを鉱酸媒体中で亜硝酸ナトリウ
ムにより処理し、得たる一般式
（式中R1は前記の意味を有する）にて示され
るニトロソアミノニトリルを鉱酸で処理して環化
し、得たる一般式
（式中R1は前記の意味を有する）にて示され
る化合物を必要に応じ酸付加塩に変じるか、又は
一般式
XCOOC2H5 （）
（式中Ｘはハロゲン原子を意味する）にて示さ
れるハロ蟻酸エチルエステルにて処理し、得たる
一般式
（式中R1は前記の意味を有する）にて示され
る化合物を必要に応じ酸付加塩に変ずることによ
り得ることができる。 According to the method of the present invention, the compound represented by the general formula and its acid addition salt can be prepared by combining formaldehyde and a cyanide compound with the general formula R 1 -NH 2 () (wherein R 1 is morphopyrrolidino, morphopiperidino or β-nicotinoylamino). An amino nitrile represented by the general formula R 1 -NH-CH 2 CN () (in which R 1 has the above-mentioned meaning) is reacted with an amine represented by Treatment with sodium nitrite in medium gives the general formula (In the formula, R 1 has the above-mentioned meaning) is treated with a mineral acid to cyclize the nitrosoaminonitrile, resulting in the general formula If necessary, the compound represented by the formula The general formula obtained by treatment with haloformic acid ethyl ester shown in It can be obtained by converting the compound represented by the formula (in which R 1 has the above-mentioned meaning) into an acid addition salt, if necessary.
本発明方法に使用されるシアン化物としてはシ
アン化水素又はシアン化カリウムが適当である。
酸付加塩を形成するための酸としては、生成する
塩が薬理学的に認容し得るものであれば良く、例
えば塩酸、臭化水素酸、燐酸等の無機酸や、マレ
イン酸、フマル酸、酒石酸、蓚酸、メタンスルホ
ン酸等の有機酸を挙げることができる。 Suitable cyanides used in the process of the invention are hydrogen cyanide or potassium cyanide.
The acid for forming the acid addition salt may be any acid as long as the resulting salt is pharmacologically acceptable, such as inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, maleic acid, fumaric acid, etc. Organic acids such as tartaric acid, oxalic acid, and methanesulfonic acid can be mentioned.
尚、一般式にて示される化合物及びその酸付
加塩は結晶化又はクロマトグラフ吸着処理により
精製することができる。 The compound represented by the general formula and its acid addition salt can be purified by crystallization or chromatographic adsorption treatment.
例 １
３−（β−ニコチノイルアミノエチル）シドノ
ンイミン・２塩酸塩
水55ml中に、Ｎ−ニコチノイルエチレンジアミ
ン14.2g（86ミリモル）と、ホルムアルデヒド・亜
硫酸水素ナトリウム・１水和物13.2g（86.6ミリモ
ル）とを添加して１時間撹拌し、次いでシアン化
カリウム5.6g（86ミリモル）を添加して50〜55℃
で３時間に亘り撹拌した。反応混合物は冷却し
て、上部の油層を除去し、残液を酢酸エチル抽出
した。この抽出物を無水硫酸ナトリウムで乾燥さ
せ、濃縮し、シリカゲルカラム処理すれば（溶出
液：酢酸エチル／メタノール）、Ｎ−シアノメチ
ル−N′−ニコチノイルエチレンジアミン8.63g（収
率49.1％）が得られる。Example 1 3-(β-nicotinoylaminoethyl)cydononeimine dihydrochloride 14.2 g (86 mmol) of N-nicotinoylethylenediamine and 13.2 g (86.6 mmol) of formaldehyde sodium bisulfite monohydrate were added to 55 ml of water, stirred for 1 hour, and then 5.6 g (86 mmol) of potassium cyanide was added. mmol) at 50-55℃
The mixture was stirred for 3 hours. The reaction mixture was cooled, the upper oil layer was removed, and the residual liquid was extracted with ethyl acetate. If this extract is dried over anhydrous sodium sulfate, concentrated, and treated with a silica gel column (eluent: ethyl acetate/methanol), 8.63 g of N-cyanomethyl-N'-nicotinoylethylenediamine (yield 49.1%) is obtained. .
次いで、水5.6ml中に上記ジアミン4.63g（22.7ミ
リモル）と濃塩酸2.3mlとを溶解させ、次いで冷
却して２〜３℃に保ち撹拌した。水2.3mlに亜硝
酸ナトリウム1.57g（22.7ミリモル）を溶解した溶
酸を上記撹拌溶液に滴下し、次いで全体を０℃で
１時間に亘り撹拌した。析出結晶を取し、乾燥
し、塩化メチレン／エーテルで再結晶させれば融
点105〜106.5℃のＮ−シアノメチル−Ｎ−ニトロ
ソ−N′−ニコチノイルエチレンジアミン2.80g（収
率52.9％）が得られる。 Next, 4.63 g (22.7 mmol) of the above diamine and 2.3 ml of concentrated hydrochloric acid were dissolved in 5.6 ml of water, then cooled, kept at 2 to 3° C., and stirred. A solution of 1.57 g (22.7 mmol) of sodium nitrite dissolved in 2.3 ml of water was added dropwise to the stirred solution, and the whole was then stirred at 0° C. for 1 hour. If the precipitated crystals are collected, dried, and recrystallized from methylene chloride/ether, 2.80 g (yield 52.9%) of N-cyanomethyl-N-nitroso-N'-nicotinoylethylenediamine with a melting point of 105-106.5°C is obtained. .
得られたこのニトリル2.5g（10.7ミリモル）に
塩酸／メタノール溶液を滴下して１時間放置した
後に濃縮し、エタノール／エーテル溶液で再結晶
させれば、所望の３−（β−ニコチノイルアミノ
エチル）シドノンイミン・２塩酸塩1.0g（収率
30.3％）が得られる。 A hydrochloric acid/methanol solution is added dropwise to 2.5 g (10.7 mmol) of the obtained nitrile, left for 1 hour, concentrated, and recrystallized from an ethanol/ether solution to obtain the desired 3-(β-nicotinoylaminoethyl). ) Sidononeimine dihydrochloride 1.0g (yield
30.3%).
融点 171〜174℃（分解）
元素分析：
理論値 C39.23 H4.28 N22.88
実測値 C39.01 H4.28 N22.78
MS ：
（CI／DI）ｍ／ｅ；234（Ｍ＋１−HCl）+，203
（EI／DI）ｍ／ｅ；234，203，176，135，106
IR（KBr）：1680（＝NH），1670（Ｃ＝０）cm-1
例 ２
３−（Ｎ−モルホピロリジノ）シドノンイミ
ン・１塩酸塩・１水和物
水45ml中に、Ｎ−アミノモルホピロリジン
24.8g（0.194モル）と、ホルムアルデヒド・亜硫
酸水素ナトリウム、１水和物29.5g（0.194モル）
とを添加して室温で１時間撹拌した。不溶物を
去し、シアン化カリウム12.6g（0.194モル）を添
加し、55℃で３時間撹拌した後に冷却して酢酸エ
チル抽出した。抽出物を無水硫酸ナトリウムで乾
燥し、濃縮し、減圧蒸留すれば、沸点99〜106
℃／0.2mmHgのＮ−シアノメチルアミノモルホピ
ロリジン21.5g（収率66.4％）が得られる。 Melting point 171-174℃ (decomposition) Elemental analysis: Theoretical value C39.23 H4.28 N22.88 Actual value C39.01 H4.28 N22.78 MS: (CI/DI) m/e; 234 (M+1-HCl) + , 203 (EI/DI) m/e; 234, 203, 176, 135, 106 IR (KBr): 1680 (=NH), 1670 (C=0) cm -1 Example 2 3-(N-morphopyrrolidino) Sidononeimine monohydrochloride monohydrate N-aminomorphopyrrolidine in 45 ml of water.
24.8g (0.194mol) and formaldehyde/sodium bisulfite, monohydrate 29.5g (0.194mol)
and stirred at room temperature for 1 hour. Insoluble matter was removed, 12.6 g (0.194 mol) of potassium cyanide was added, and the mixture was stirred at 55°C for 3 hours, cooled, and extracted with ethyl acetate. If the extract is dried over anhydrous sodium sulfate, concentrated, and distilled under reduced pressure, the boiling point is 99-106.
21.5 g (66.4% yield) of N-cyanomethylaminomorphopyrrolidine with a temperature of 0.2 mmHg is obtained.
このモルホピロリジンの塩酸塩9.5g（0.0467モ
ル）を水40mlに溶解し、水５mlに亜硝酸ナトリウ
ム3.54g（0.0514モル）を溶解した溶液を０℃で且
つアルゴン気流化に滴下した。この滴下後１時間
撹拌した後に、生成した黄色結晶を取し、冷水
で洗浄すれば、Ｎ−（Ｎ−シアノメチル−Ｎ−ニ
トロソアミノ）モルホピロリジン6.5g（収率71.0
％）が得られる。 9.5 g (0.0467 mol) of this morphopyrrolidine hydrochloride was dissolved in 40 ml of water, and a solution of 3.54 g (0.0514 mol) of sodium nitrite dissolved in 5 ml of water was added dropwise at 0° C. under an argon atmosphere. After stirring for 1 hour after this dropwise addition, the yellow crystals formed were collected and washed with cold water to yield 6.5 g of N-(N-cyanomethyl-N-nitrosamino)morphopyrrolidine (yield 71.0).
%) is obtained.
得られたこのニトリル6.5g（0.0332モル）をメ
タノール50mlに溶解させ、3N−塩酸性メタノー
ル溶液31mlを滴下して１時間撹拌した後にエーテ
ルを滴下して結晶化させれば、所望の３−（Ｎ−
モルホピロリジノ）シドノンイミン・１塩酸塩・
１水和物6.2g（収率74.5％）が得られる。 By dissolving 6.5 g (0.0332 mol) of the obtained nitrile in 50 ml of methanol, adding 31 ml of 3N-hydrochloric methanol solution dropwise and stirring for 1 hour, adding ether dropwise to crystallize, the desired 3-( N-
morphopyrrolidino) sydnonimine monohydrochloride
6.2 g (yield 74.5%) of monohydrate are obtained.
融点 145〜147℃
元素分析：
理論値 C38.33 H6.03 N22.35
実測値 C38.33 H5.95 N22.42
MS ：
（CI／DI）ｍ／ｅ；168（Ｍ−28）+，166（Ｍ−
30）+
（EI／DI）ｍ／ｅ；196（Ｍ）+
IR（KBr）；3450，3050，1680，1140，885cm-1
例 ３
３−（Ｎ−モルホピペリジノ）シドノンイミ
ン・１塩酸塩
水32.5ml中に、Ｎ−アミノモルホピペリジン
17.1g（0.12モル）と、ホルムアルデヒド・亜硫酸
水素ナトリウム・１水和物18.3g（0.12モル）とを
添加して室温で１時間撹拌した。次いで不溶物を
去し、シアン化カリウム7.83g（0.12モル）を添
加し、50〜55℃で３時間撹拌した後に一夜放置す
る。析出結晶を取し、水洗すればＮ−シアノメ
チルアミノモルホピペリジン13.0g（収率59.9％）
が得られる。 Melting point 145-147℃ Elemental analysis: Theoretical value C38.33 H6.03 N22.35 Actual value C38.33 H5.95 N22.42 MS: (CI/DI) m/e; 168 (M-28) + , 166 (M-
30) + (EI/DI) m/e; 196 (M) + IR (KBr); 3450, 3050, 1680, 1140, 885 cm -1 example 3 3-(N-morphopiperidino) sydonone imine monohydrochloride N-aminomorphopiperidine in 32.5 ml of water.
17.1 g (0.12 mol) and 18.3 g (0.12 mol) of formaldehyde sodium bisulfite monohydrate were added and stirred at room temperature for 1 hour. Next, insoluble materials were removed, 7.83 g (0.12 mol) of potassium cyanide was added, and the mixture was stirred at 50 to 55°C for 3 hours and left overnight. Take the precipitated crystals and wash them with water to obtain 13.0 g of N-cyanomethylaminomorphopiperidine (yield 59.9%)
is obtained.
このモルホピペリジン4.6g（0.0211モル）を水
20mlに溶解させ、水２mlに亜硝酸ナトリウム1.6g
（0.0233モル）を溶解した溶液を０℃で且つアル
ゴン気流下に滴下した。この滴下後１時間撹拌し
た後に、析出結晶を取し、冷水で洗浄すれば、
Ｎ−（Ｎ−シアノメチル−Ｎ−ニトロソアミノ）
モルホピペリジン4.3g（収率97.0％）が得られる。 Add 4.6g (0.0211mol) of this morphopiperidine to water.
1.6g of sodium nitrite dissolved in 20ml of water
(0.0233 mol) was added dropwise at 0° C. under an argon stream. After stirring for 1 hour after this dropwise addition, the precipitated crystals are collected and washed with cold water.
N-(N-cyanomethyl-N-nitrosamino)
4.3 g of morphopiperidine (yield 97.0%) is obtained.
このニトリル4.3g（0.0205モル）を塩酸性メタ
ノール溶液で処理し、エチルエーテルで結晶化さ
せれば、所望の３−（Ｎ−モルホピペリジノシド
ノンイミン・１塩酸塩4.9g（収率97.0％）が得ら
れる。 If 4.3 g (0.0205 mol) of this nitrile is treated with a methanol solution of hydrochloric acid and crystallized with ethyl ether, 4.9 g (yield 97.0 %) is obtained.
融点142〜145℃
元素分析：
理論値 C43.82 H6.13 N22.71
実測値 C43.71 H6.11 N22.33
MS ：
（CI／DI）ｍ／ｅ；182（Ｍ−28）+，180（Ｍ−
30）
（EI／DI）ｍ／ｅ；210（Ｍ）+
IR（KBr）：3450，3075，1685，1080cm-1
例 ４
３−モルホピロリジノ−Ｎ−カルボエトキシシ
ドノンイミン
例２に記載の方法により得たるシドノンイミン
化合物3.3g（0.0132モル）を乾燥ピリジン16mlに
溶解させ、この溶液に０℃でクロル蟻酸エチルエ
ステル5.3g（0.0488モル）を滴下し、次いで室温
で一夜撹拌した。析出固体を去し、液を濃縮
し、エタノールを添加した後に再び濃縮した。こ
れをシリカゲルカラム処理し（溶出液：塩化メチ
レン）、塩化メチレン／エーテルで再結晶化すれ
ば、所望の３−モルホピロリジノ−Ｎ−カルボエ
トキシシドノンイミン2.4g（収率67.8％）が得ら
れる。 Melting point 142-145℃ Elemental analysis: Theoretical value C43.82 H6.13 N22.71 Actual value C43.71 H6.11 N22.33 MS: (CI/DI) m/e; 182 (M-28) + , 180 (M-
30) (EI/DI) m/e; 210 (M) + IR (KBr): 3450, 3075, 1685, 1080 cm -1 example 4 3-morphopyrrolidino-N-carboethoxysydnonimine 3.3 g (0.0132 mol) of the sydnonimine compound obtained by the method described in Example 2 was dissolved in 16 ml of dry pyridine, and 5.3 g (0.0488 mol) of ethyl chloroformate was added dropwise to this solution at 0°C, followed by stirring overnight at room temperature. did. The precipitated solid was removed, the liquid was concentrated, and after adding ethanol, it was concentrated again. This is treated with a silica gel column (eluent: methylene chloride) and recrystallized from methylene chloride/ether to obtain 2.4 g (yield: 67.8%) of the desired 3-morphopyrrolidino-N-carboethoxysydnonimine.
融点 90〜91℃
元素分析：
理論値 C49.25 H6.01 N20.88
実測値 C49.26 H6.06 N20.88
MS ：
（CI／DI）ｍ／ｅ；269（Ｍ＋１）+
（EI／DI）ｍ／ｅ；268（Ｍ）+，238（Ｍ−30）+，
194（Ｍ−74）+
IR（KBr）：3135，1660（Ｃ＝Ｏ），1585，1268，
1074（Ｃ−Ｏ−Ｃ），968cm-1
例 ５
３−モルホピペリジノ−Ｎ−カルボエトキシシ
ドノンイミン
例３に記載の方法により得たるシドノンイミン
化合物3.0g（0.0122モル）を乾燥ピリジン15mlに
溶解させ、この溶液に０℃でクロル蟻酸エチルエ
ステル4.5g（0.0415モル）を滴下し、次いで例４
に記載の処理を同様にして行なえば、所望の３−
モルホピペリジノ−Ｎ−カルボエトキシシドノン
イミン2.0g（収率58.1％）が得られる。Melting point 90-91℃ Elemental analysis: Theoretical value C49.25 H6.01 N20.88 Actual value C49.26 H6.06 N20.88 MS: (CI/DI) m/e; 269 (M+1) + (EI/DI ) m/e; 268 (M) + , 238 (M-30) + ,
194 (M-74) + IR (KBr): 3135, 1660 (C=O), 1585, 1268,
1074 (C-O-C), 968 cm -1 Example 5 3-morphopiperidino-N-carboethoxysidononimine 3.0 g (0.0122 mol) of the sydnonimine compound obtained by the method described in Example 3 was dissolved in 15 ml of dry pyridine, 4.5 g (0.0415 mol) of ethyl chloroformate was added dropwise to this solution at 0°C, and then 4.5 g (0.0415 mol) of chloroformic acid ethyl ester was added dropwise to this solution at 0°C.
If the process described in 2 is performed in the same way, the desired 3-
2.0 g (yield 58.1%) of morphopiperidino-N-carboethoxysydnonimine is obtained.
融点 111〜111.5℃
元素分析：
理論値 C51.06 H6.43 N19.85
実測値 C50.97 H6.59 N19.87
MS ：
（CI／DI）ｍ／ｅ；283（Ｍ＋１）+
（EI／DI）ｍ／ｅ；282（Ｍ）+，252（Ｍ−30）+，
208（Ｍ−74）+
IR（KBr）：3145（シドノンＣ−Ｈ），3000（Ｃ−
Ｈ），1650（Ｃ＝Ｏ），1570（Ｎ−COO），1270，
1080（Ｃ−Ｏ−Ｃ）cm-1 Melting point 111-111.5℃ Elemental analysis: Theoretical value C51.06 H6.43 N19.85 Actual value C50.97 H6.59 N19.87 MS: (CI/DI) m/e; 283 (M+1) + (EI/DI ) m/e; 282 (M) + , 252 (M-30) + ,
208 (M-74) + IR (KBr): 3145 (Sydonone C-H), 3000 (C-
H), 1650 (C=O), 1570 (N-COO), 1270,
1080(C-O-C)cm -1
Claims (1)
ジノ又はβ−ニコチノイルアミノエチル基を意味
し、R2は水素又はカルボエトキシ基を意味する）
にて示される新規なシドノンイミン化合物又はそ
の酸付加塩。 ２ ホルムアルデヒド及びシアン化合物を一般式 R1−NH2 （） （式中R1はモルホピロリジノ、モルホピペリ
ジノ又はβ−ニコチノイルアミノエチル基を意味
する）にて示されるアミンと反応させ、得たる一
般式 R1−NH−CH2CN （） （式中R1は前記の意味を有する）にて示され
るアミノニトリルを鉱酸媒体中で亜硝酸ナトリウ
ムにより処理し、得たる一般式 （式中R1は前記の意味を有する）にて示され
るニトロソアミノニトリルを鉱酸で処理して環化
し且つ必要に応じ酸付加塩に変ずることを特徴と
する、 一般式 （式中R1は前記の意味を有する）にて示され
る新規なシドノンイミン化合物又はその酸付加塩
の製法。 ３ ホルムアルデヒド及びシアン化合物を一般式 R1−NH2 （） （式中R1はモルホピロリジノ、モルホピペリ
ジノ又はβ−ニコチノイルアミノエチル基を意味
する）にて示されるアミンと反応させ、得たる一
般式 R1−NH−CH2CN （） （式中R1は前記の意味を有する）にて示され
るアミノニトリルを鉱酸媒体中で亜硝酸ナトリウ
ムにより処理し、得たる一般式 （式中R1は前記の意味を有する）にて示され
るニトロソアミノニトリルを鉱酸で処理して環化
し、得たる一般式 （式中R1は前記の意味を有する）にて示され
る化合物を一般式 XCOOC2H5 （） （式中Ｘはハロゲン原子を意味する）にて示さ
れるハロ蟻酸エステルと反応させ且つ必要に応じ
酸付加塩に変ずることを特徴とする、一般式 （式中R1は前記の意味を有する）にて示され
る新規なシドノンイミン化合物又はその酸付加塩
の製法。[Claims] 1. General formula (In the formula, R 1 means morphopyrrolidino, morphopiperidino or β-nicotinoylaminoethyl group, and R 2 means hydrogen or carboethoxy group)
A novel sydnonimine compound or an acid addition salt thereof shown in 2 Formaldehyde and a cyanide compound are reacted with an amine represented by the general formula R 1 -NH 2 (in the formula, R 1 means morphopyrrolidino, morphopiperidino or β-nicotinoylaminoethyl group) to obtain the general formula R The general formula obtained by treating aminonitrile represented by 1 -NH-CH 2 CN () (in which R 1 has the above-mentioned meaning) with sodium nitrite in a mineral acid medium (wherein R 1 has the above-mentioned meaning) is treated with a mineral acid to cyclize the nitrosoaminonitrile and, if necessary, convert it into an acid addition salt. A method for producing a novel sydnonimine compound or an acid addition salt thereof represented by the formula (wherein R 1 has the above-mentioned meaning). 3 Formaldehyde and a cyanide compound are reacted with an amine represented by the general formula R 1 -NH 2 (in the formula, R 1 means morphopyrrolidino, morphopiperidino or β-nicotinoylaminoethyl group) to obtain the general formula R The general formula obtained by treating aminonitrile represented by 1 -NH-CH 2 CN () (in which R 1 has the above-mentioned meaning) with sodium nitrite in a mineral acid medium (In the formula, R 1 has the above-mentioned meaning) is treated with a mineral acid to cyclize the nitrosoaminonitrile, resulting in the general formula (in the formula, R 1 has the above-mentioned meaning) is reacted with a haloformic acid ester represented by the general formula XCOOC 2 H 5 () (in the formula, X means a halogen atom), and A general formula characterized by the ability to transform into acid addition salts depending on A method for producing a novel sydnonimine compound or an acid addition salt thereof represented by the formula (wherein R 1 has the above-mentioned meaning).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20602282A JPS5998076A (en) | 1982-11-26 | 1982-11-26 | Novel sydnoneimine compound and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20602282A JPS5998076A (en) | 1982-11-26 | 1982-11-26 | Novel sydnoneimine compound and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5998076A JPS5998076A (en) | 1984-06-06 |
| JPH0359905B2 true JPH0359905B2 (en) | 1991-09-12 |
Family
ID=16516599
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20602282A Granted JPS5998076A (en) | 1982-11-26 | 1982-11-26 | Novel sydnoneimine compound and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5998076A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3820210A1 (en) * | 1988-06-14 | 1989-12-21 | Cassella Ag | SUBSTITUTED 3-AMINO-DYNONOMINES, PROCESS FOR THEIR PREPARATION AND THEIR USE |
-
1982
- 1982-11-26 JP JP20602282A patent/JPS5998076A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5998076A (en) | 1984-06-06 |
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