JPH02180876A - Production of 1-((1-pyrrolidinylcarbonyl)methyl)-4-(3,4,5-trimethoxycinnamoyl)piperazine - Google Patents
Production of 1-((1-pyrrolidinylcarbonyl)methyl)-4-(3,4,5-trimethoxycinnamoyl)piperazineInfo
- Publication number
- JPH02180876A JPH02180876A JP63333971A JP33397188A JPH02180876A JP H02180876 A JPH02180876 A JP H02180876A JP 63333971 A JP63333971 A JP 63333971A JP 33397188 A JP33397188 A JP 33397188A JP H02180876 A JPH02180876 A JP H02180876A
- Authority
- JP
- Japan
- Prior art keywords
- pyrrolidinylcarbonyl
- trimethoxycinnamoyl
- piperazine
- methyl
- formula
- 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
- 238000004519 manufacturing process Methods 0.000 title description 3
- RCUDFXMNPQNBDU-VOTSOKGWSA-N cinepazide Chemical compound COC1=C(OC)C(OC)=CC(\C=C\C(=O)N2CCN(CC(=O)N3CCCC3)CC2)=C1 RCUDFXMNPQNBDU-VOTSOKGWSA-N 0.000 title 1
- -1 3,4,5- trimethoxycinnamoyl Chemical group 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 239000000126 substance Substances 0.000 claims abstract description 4
- 150000003512 tertiary amines Chemical class 0.000 claims abstract description 4
- KYBCXTTWIOZBNR-UHFFFAOYSA-N 2-piperazin-1-yl-1-pyrrolidin-1-ylethanone Chemical compound C1CCCN1C(=O)CN1CCNCC1 KYBCXTTWIOZBNR-UHFFFAOYSA-N 0.000 claims abstract 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 28
- 150000004820 halides Chemical class 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 abstract description 9
- 150000001875 compounds Chemical class 0.000 abstract description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 abstract description 4
- 239000003960 organic solvent Substances 0.000 abstract description 4
- 230000002490 cerebral effect Effects 0.000 abstract description 3
- 230000004060 metabolic process Effects 0.000 abstract description 3
- XSTJTOKYCAJVMJ-GVTSEVKNSA-N (z)-but-2-enedioic acid;(e)-1-[4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one Chemical compound OC(=O)\C=C/C(O)=O.COC1=C(OC)C(OC)=CC(\C=C\C(=O)N2CCN(CC(=O)N3CCCC3)CC2)=C1 XSTJTOKYCAJVMJ-GVTSEVKNSA-N 0.000 abstract description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 abstract description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 abstract description 2
- 229960004201 cinepazide Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 abstract description 2
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 abstract description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 abstract 1
- 238000000034 method Methods 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FZLSDZZNPXXBBB-KDURUIRLSA-N 5-chloro-N-[3-cyclopropyl-5-[[(3R,5S)-3,5-dimethylpiperazin-1-yl]methyl]phenyl]-4-(6-methyl-1H-indol-3-yl)pyrimidin-2-amine Chemical compound C[C@H]1CN(Cc2cc(Nc3ncc(Cl)c(n3)-c3c[nH]c4cc(C)ccc34)cc(c2)C2CC2)C[C@@H](C)N1 FZLSDZZNPXXBBB-KDURUIRLSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 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
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は式（１）で示される、１−（（１−ピロリジニ
ルカルボニル）メチル）−４−（８，４，５−トリメト
キシシンナモイル）ピペラジン又はそのハロゲン化水素
酸塩を製造する方法に関する。Detailed Description of the Invention (Industrial Application Field) The present invention relates to 1-((1-pyrrolidinylcarbonyl)methyl)-4-(8,4,5-trimethoxy The present invention relates to a method for producing cinnamoyl)piperazine or its hydrohalide salt.
本発明で製造される１−（（１−ピロリジニルカルボニ
ル）メチル）−４−（８，４，５−トリメトキシシンナ
モイル）ピペラジンのマレイン酸塩は優れた脳循環代謝
改善剤として広く使用されており有用な化合物である。The maleate salt of 1-((1-pyrrolidinylcarbonyl)methyl)-4-(8,4,5-trimethoxycinnamoyl)piperazine produced by the present invention is widely used as an excellent cerebral circulation and metabolism improving agent. It is a useful compound.
（従来技術並びに本発明が解決しようとする課題）従来
、１−（（１−ピロリジニルカルボニル）メチル）−４
−（８，４，５−トリメトキシシンナモイル）ピペラジ
ンの製造法としては、！−（（１−ピロリジニルカルボ
ニル）メチルコピぺる炭酸ナトリウムもしくは炭素水素
ナトリウムの存在下に反応させる方法が特公昭４７−１
２９８号公報に記載されている。しかしながら、この方
法は収率が６５％と低く未だ十分な工業的製法とは言い
難い。(Prior art and problems to be solved by the present invention) Conventionally, 1-((1-pyrrolidinylcarbonyl)methyl)-4
-(8,4,5-trimethoxycinnamoyl)piperazine production method is! -((1-Pyrrolidinylcarbonyl)methylcopypereacting method in the presence of sodium carbonate or sodium carbonate
It is described in the No. 298 publication. However, this method has a low yield of 65% and is still not considered to be an adequate industrial production method.
本発明の目的は高収率で１−（（１−ピロリジニルカル
ボニル）メチル）−４−（８，４，５−トリメトキシシ
ンナモイル）ピペラジン又はそのハロゲン化水素酸塩を
得る方法を提供することにある。An object of the present invention is to provide a method for obtaining 1-((1-pyrrolidinylcarbonyl)methyl)-4-(8,4,5-trimethoxycinnamoyl)piperazine or its hydrohalide salt in high yield. It's about doing.
（ｖＡ題を解決する為の手段）
本発明者は、上記のごとき実情に鑑み鋭意研究を重ねた
結果、驚くべきことに、式（ｎ）で表わされる１−［（
１−ピロリジニルカルボニル）メチルコピペラジンと一
般代＠）
（式中Ｘはハロゲン原子を示す）
で表わされる８、４．５−１リメトキシシンナモイルハ
ロゲニドを第８級アミンの存在下に反応せしめることに
より、目的化合物を公知方法よりも格段に優れた高収率
で製造できることを見出し、本発明を完成した。(Means for Solving the vA Problem) As a result of extensive research in view of the above-mentioned circumstances, the present inventor surprisingly discovered that 1-[(
1-pyrrolidinylcarbonyl) methylcopiperazine and the general group @) (in the formula, X represents a halogen atom) 8,4.5-1 rimethoxycinnamoyl halide represented by The present invention was completed based on the discovery that the target compound can be produced in a much higher yield than known methods by reacting the compound.
すなわち、本発明は
で表わされる１−（（１−ピロリジニルカルボニル）メ
チルコピペラジンと一般式
（式中、Ｘはハロゲン原子を示す）で表わされる８、４
．５−トリメトキシシンナモイルハロゲニドを第８級ア
ミンの存在下に反応せしめることを特徴とする１−（（
１−ピロリジニルカルボニル）メチル）−４−（８，４
，５−トリメトキシシンナモイル）ピペラジン又はその
ハロゲン化水素酸塩の製造法である。That is, the present invention relates to 1-((1-pyrrolidinylcarbonyl)methylcopiperazine represented by) and 8,4 represented by the general formula (wherein, X represents a halogen atom)
．． 1-(((
1-pyrrolidinylcarbonyl)methyl)-4-(8,4
, 5-trimethoxycinnamoyl)piperazine or its hydrohalide salt.
ところで、本発明の弱塩基性物質である第３ｇアミンは
、公知方法の炭酸ナトリウム及び炭酸水素ナトリウムの
酸結合剤としての作用とは異なる触媒的作用をなし、こ
れにより目的物質の収率が公知方法に比べて極めて高く
なっているものと推考される。By the way, the tertiary amine, which is a weakly basic substance of the present invention, has a catalytic effect that is different from the action of sodium carbonate and sodium bicarbonate as acid binders in known methods, and as a result, the yield of the target substance can be increased to a known level. It is assumed that the cost is extremely high compared to the method.
第８級アミンとしてはトリエチルアミン、トリプロピル
アミン、トリブチルア疋ン等の脂肪族アミン、ピリジン
、ピコリン類、ルチジン類、モルホリン等の含窒素複素
環化合物などが挙げられる。Examples of the 8th-class amine include aliphatic amines such as triethylamine, tripropylamine, and tributylamine, and nitrogen-containing heterocyclic compounds such as pyridine, picolines, lutidines, and morpholine.
第８級アミンの使用量は、通常１−（（１−ピロリジニ
ルカルボニル）メチルコピペラジンに対して１．０〜５
０倍モル量であり、好ましくは２．０〜２０倍モル量で
ある。The amount of 8th class amine used is usually 1.0 to 5.
It is 0 times the molar amount, preferably 2.0 to 20 times the molar amount.
８．４．５−トリメトキシシンナモイルハロゲニドとし
ては、８，４．５−トリメトキシシンナモイルクロライ
ド、８，４．５−トリメトキシシンナモイルブロマイド
、８，４．５−トリメトキシシンナモイルアイオダイド
が挙げられる。８゜４．５−トリメトキシシンナモイル
ハロゲニドは１−（（１−ピロリジニルカルボニル）メ
チルコピペラジン（Ｉ［）に対して１．０〜２．５倍モ
ル量で使用するのが好ましい。8.4.5-Trimethoxycinnamoyl halogenide includes 8,4.5-trimethoxycinnamoyl chloride, 8,4.5-trimethoxycinnamoyl bromide, 8,4.5-trimethoxycinnamoyl iodine. One example is Dido. 8゜4.5-Trimethoxycinnamoyl halide is preferably used in a molar amount of 1.0 to 2.5 times that of 1-((1-pyrrolidinylcarbonyl)methylcopiperazine (I[)). .
本発明方法においては、不活性有機溶媒中で反応を実施
するのが好ましく、かかる溶媒としては、特に限定され
るものではないが通常ベンゼン、トルエン、キシレン等
の芳香族炭化水素、アセトン、テトラヒドロフラン、ジ
オキサン、クロロホルム等のそれぞれ単独あるいはそれ
らの二種類以上の混合溶媒が好ましい。不活性有機溶媒
の使用量は、通常１−（（１−ピロリジニルカルボニル
）メチルコピペラジンに対して１．０〜５０倍重量であ
り、好ましくは８．０〜２０倍重量である。In the method of the present invention, it is preferable to carry out the reaction in an inert organic solvent, and such solvents include, but are not particularly limited to, aromatic hydrocarbons such as benzene, toluene, and xylene, acetone, tetrahydrofuran, Preferable solvents include dioxane, chloroform, etc. alone or a mixture of two or more thereof. The amount of the inert organic solvent used is usually 1.0 to 50 times the weight of 1-((1-pyrrolidinylcarbonyl)methylcopiperazine), preferably 8.0 to 20 times the weight of 1-((1-pyrrolidinylcarbonyl)methylcopiperazine).
本発明方法の好ましい一実施態様を挙げれば、通常室温
〜１５０℃好、ましくは５０〜１２０℃に保った８、４
．５−トリメトキシシンナモイルハロゲニド、第８級ア
ミン及び不活性有機溶媒からなる混合物に、該温度を保
ちながらｔ−（Ｃｔ−ピロリジニルカルボニル）メチル
コピペラジン又はこれと第８級アミンとの混合物を徐々
に滴下し、滴下終了後肢温度に１〜２４時間程度保てば
よい。To give a preferred embodiment of the method of the present invention, 8, 4
．． t-(Ct-pyrrolidinylcarbonyl)methylcopiperazine or its combination with a 8th-class amine is added to a mixture of 5-trimethoxycinnamoyl halide, a 8th-class amine, and an inert organic solvent while maintaining the temperature. The mixture is gradually added dropwise, and the temperature of the hind limbs is maintained for about 1 to 24 hours after the addition.
１−（（１−ピロリジニルカルボニル）メチル〕−４−
（８，４，５−）リメトキシシンナモイル）ピペラジン
のハロゲン化水素酸塩は反応液を冷却すれば析出し、反
応液から単離することができる。1-((1-pyrrolidinylcarbonyl)methyl)-4-
The hydrohalide salt of (8,4,5-rimethoxycinnamoyl)piperazine precipitates when the reaction solution is cooled and can be isolated from the reaction solution.
このようにして得られた１−（（１−ピロリジニルカル
ボニル）メチル）−４−（８，４，５−トリメトキシシ
ンナモイル）ピペラジンのハロゲン化水素酸塩をアルカ
リ水溶液で処理すれば、１−〔（１−ピロリジニルカル
ボニル）メチル〕−４−（８，４，５−トリメトキシシ
ンナモイル）ピペラジンが析出し、単離できる。単離さ
れた１−〔（１−ピロリジニルカルボニル）メチル〕−
４（８，４，５−トリメトキシシンナモイル）ピペラジ
ン及びそのハロゲン化水素酸塩は再結晶等の慣用手段に
より容易に精製することができる。If the hydrohalide salt of 1-((1-pyrrolidinylcarbonyl)methyl)-4-(8,4,5-trimethoxycinnamoyl)piperazine thus obtained is treated with an aqueous alkali solution, 1-[(1-pyrrolidinylcarbonyl)methyl]-4-(8,4,5-trimethoxycinnamoyl)piperazine precipitates and can be isolated. isolated 1-[(1-pyrrolidinylcarbonyl)methyl]-
4(8,4,5-trimethoxycinnamoyl)piperazine and its hydrohalide salt can be easily purified by conventional means such as recrystallization.
（発明の効果）
本発明方法によると優れた脳循環代謝改善作用を有する
医薬品として広く使用されているマレイン酸シネパジド
のマレイン酸フリ一体である１−〔（１−ピロリジニル
カルボニル）メチル〕−４−（８，４，５−トリメトキ
シシンナモイル）ピペラジンが極めて高収率で得ること
が出来、従来法と比較して工業的に生産性、経済性が著
しく改善される。(Effects of the Invention) According to the method of the present invention, 1-[(1-pyrrolidinylcarbonyl)methyl]-, which is a maleic acid monomer of cinepazide maleate, which is widely used as a drug with excellent cerebral circulation and metabolism improving effects. 4-(8,4,5-trimethoxycinnamoyl)piperazine can be obtained in extremely high yield, and industrial productivity and economy are significantly improved compared to conventional methods.
（実施例）
以下（こ実施例を挙げ、本発明を説明するが、本発明は
これらに限定されるものではない。(Example) The present invention will be described below with reference to Examples, but the present invention is not limited thereto.
実施例−１
８，４，５−トリメトキシシンナモイルクロライド１５
．６Ｆに無水ピリジン１０２及びトルエン８０２を加え
攪拌下８０℃に加熱する。この中に無水ピリジン４０９
に溶解した１−（１−（ピロリジニルカルボニル）メチ
ルコピペラジン１０．０７を滴下する。滴下終了後８０
℃で５時間保つ。Example-1 8,4,5-trimethoxycinnamoyl chloride 15
．． Anhydrous pyridine 102 and toluene 802 are added to 6F and heated to 80°C while stirring. In this, anhydrous pyridine 409
Add dropwise 10.07 g of 1-(1-(pyrrolidinylcarbonyl)methylcopiperazine) dissolved in
Keep at ℃ for 5 hours.
冷却後反応晶出物２４．１９を濾過乾燥した後、水１６
０ノ及び５％炭酸ナトリウム水溶液２００ｙを加え室温
下で攪拌する。生じた結晶を濾過乾燥するとｍ、ｐ、１
０８〜１１０℃を示す１−（（１−ピロリジニルカルボ
ニル）メチル）−４−（８゜４．５−トリメトキシシン
ナモイル）ピペラジン２０．５ｙを得る（収率９６．８
％）。氷晶は公知方法で得た標品と各種スペクトルデー
タの比較および混融論験によりその構造を確認した。After cooling, the reaction crystallized product 24.19 was filtered and dried, and water 16
Add 200 y of 0 and 5% aqueous sodium carbonate solution and stir at room temperature. When the formed crystals are filtered and dried, m, p, 1
20.5y of 1-((1-pyrrolidinylcarbonyl)methyl)-4-(8°4.5-trimethoxycinnamoyl)piperazine having a temperature of 08 to 110°C was obtained (yield 96.8
%). The structure of the ice crystals was confirmed by comparing various spectral data with specimens obtained by known methods and by conducting mixed melting experiments.
実施例−２
８，４，５−）リメトキシシンナモイルクロライド１６
．９５’に無水ピリジン５０ノ及びキシレン８０９を加
え攪拌下８０℃に加熱する。この中に１＝しく１−ピロ
リジニルカルボニル）メチルコピペラジン１０ノを滴下
する。滴下終了後８０℃で５時間保つ。冷却後反応晶出
物２８．８９を濾過乾燥した後、水１００７及び５％炭
酸ナトリウム水溶ｆｉ２００９を加え室温下で攪拌する
。生じた結晶を濾過乾燥するとｍ、ｐ、１０７〜１１０
℃を示ｔｌ （（１−ピロリジニルカルボニル）メチ
ル）−４−（８，４，５−トリメトキシシンナモイル）
ピペラジン２０．０９を得る（収率９４，４％）。Example-2 8,4,5-) Rimethoxycinnamoyl chloride 16
．． 50 parts of anhydrous pyridine and 80 parts of xylene were added to 95' and heated to 80°C with stirring. 10 pieces of 1=1-pyrrolidinylcarbonyl)methylcopiperazine are added dropwise to the solution. After completion of dropping, keep at 80°C for 5 hours. After cooling, the reaction crystallized product 28.89 was filtered and dried, and then water 1007 and 5% sodium carbonate aqueous fi2009 were added and stirred at room temperature. When the resulting crystals are filtered and dried, m, p, 107-110
tl ((1-pyrrolidinylcarbonyl)methyl)-4-(8,4,5-trimethoxycinnamoyl)
20.09 of piperazine is obtained (yield 94.4%).
氷晶は公知方法で得た標品と各皿スペクトルデータの比
較および混融試験によりその構造を確認した。The structure of the ice crystals was confirmed by comparing the spectrum data of each dish with a specimen obtained by a known method and by a melting test.
実施例−８
８，４，５−トリメトキシシンナモイルクロライド８１
．２９にトリエチルアミン６（ｌ及びトルエン１６０Ｆ
を加え攪拌下８０℃に加熱する。この中に１−（Ｃ１−
ピロリジニルカルボニル）メチルコピペラジン２０９を
滴下する。滴下終了後８０℃で１２時間保つ。冷却後反
応晶出物４７．０ノを濾過乾燥した後、水８００９及び
５％炭酸ナトリウム水溶液４００９を加え室温下で攪拌
する。Example-8 8,4,5-trimethoxycinnamoyl chloride 81
．． 29, triethylamine 6 (l) and toluene 160F
and heated to 80°C while stirring. In this, 1-(C1-
pyrrolidinylcarbonyl)methylcopiperazine 209 is added dropwise. After completion of dropping, keep at 80°C for 12 hours. After cooling, 47.0 g of the reaction crystallized product was filtered and dried, and then 8009 g of water and 4009 g of a 5% aqueous sodium carbonate solution were added, followed by stirring at room temperature.
生じた結晶を濾過乾燥するとｍ、ｐ、 １０７〜１１０
０Ｃを示ｔｌ （（１−ピロリジニルカルボニル）メ
チル）−４−（８，４，５−トリメトキシシンナモイル
）ピペラジン８８．２ｙを得る（収率９０，２％）。氷
晶は公知方法で得た標品と各種スペクトルデータの比較
および混融試験によりその構造を確認した。When the resulting crystals are filtered and dried, m, p, 107-110
88.2y of ((1-pyrrolidinylcarbonyl)methyl)-4-(8,4,5-trimethoxycinnamoyl)piperazine is obtained (yield 90.2%). The structure of the ice crystals was confirmed by comparing various spectral data with standard specimens obtained by known methods and by performing mixing tests.
Claims (1)
チル〕ピペラジンと一般式 ▲数式、化学式、表等があります▼ （式中、Ｘはハロゲン原子を示す）で表わされる３，４
，５−トリメトキシシンナモイルハロゲニドを第３級ア
ミンの存在下に反応せしめることを特徴とする１−〔（
１−ピロリジニルカルボニル）メチル〕−４−（３，４
，６−トリメトキシシンナモイル）ピペラジン又はその
ハロゲン化水素酸塩の製造法。[Claims] 1-[(1-pyrrolidinylcarbonyl)methyl]piperazine represented by the formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ and the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula , X represents a halogen atom)
, 5-trimethoxycinnamoyl halide in the presence of a tertiary amine.
1-pyrrolidinylcarbonyl)methyl]-4-(3,4
, 6-trimethoxycinnamoyl)piperazine or its hydrohalide salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63333971A JPH02180876A (en) | 1988-12-29 | 1988-12-29 | Production of 1-((1-pyrrolidinylcarbonyl)methyl)-4-(3,4,5-trimethoxycinnamoyl)piperazine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63333971A JPH02180876A (en) | 1988-12-29 | 1988-12-29 | Production of 1-((1-pyrrolidinylcarbonyl)methyl)-4-(3,4,5-trimethoxycinnamoyl)piperazine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02180876A true JPH02180876A (en) | 1990-07-13 |
Family
ID=18272040
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63333971A Pending JPH02180876A (en) | 1988-12-29 | 1988-12-29 | Production of 1-((1-pyrrolidinylcarbonyl)methyl)-4-(3,4,5-trimethoxycinnamoyl)piperazine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02180876A (en) |
-
1988
- 1988-12-29 JP JP63333971A patent/JPH02180876A/en active Pending
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