JPS58189170A - 1-(3,4,5-trimethoxycinnamoyl)-4-aminocarbonyl-ethyl- substituted piperazine and homopiperazine derivative and its preparation - Google Patents
1-(3,4,5-trimethoxycinnamoyl)-4-aminocarbonyl-ethyl- substituted piperazine and homopiperazine derivative and its preparationInfo
- Publication number
- JPS58189170A JPS58189170A JP57071471A JP7147182A JPS58189170A JP S58189170 A JPS58189170 A JP S58189170A JP 57071471 A JP57071471 A JP 57071471A JP 7147182 A JP7147182 A JP 7147182A JP S58189170 A JPS58189170 A JP S58189170A
- Authority
- JP
- Japan
- Prior art keywords
- solution
- homopiperazine
- spectrum
- general formula
- chloroform
- 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
- -1 1-(3,4,5-trimethoxycinnamoyl)-4-aminocarbonyl-ethyl- substituted piperazine Chemical class 0.000 title claims description 16
- 150000004050 homopiperazines Chemical class 0.000 title claims description 10
- 238000000034 method Methods 0.000 claims abstract description 28
- 239000002253 acid Substances 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 125000003277 amino group Chemical group 0.000 claims abstract description 10
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 92
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 47
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 150000004885 piperazines Chemical class 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims 1
- 229930006000 Sucrose Natural products 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 239000005720 sucrose Substances 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 abstract description 87
- 238000010992 reflux Methods 0.000 abstract description 34
- 150000001875 compounds Chemical class 0.000 abstract description 17
- 239000003960 organic solvent Substances 0.000 abstract description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 4
- 229940124549 vasodilator Drugs 0.000 abstract description 2
- 239000003071 vasodilator agent Substances 0.000 abstract description 2
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 154
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 125
- 239000000243 solution Substances 0.000 description 89
- 238000001228 spectrum Methods 0.000 description 55
- 239000007788 liquid Substances 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 238000003756 stirring Methods 0.000 description 41
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
- 239000013078 crystal Substances 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 239000000203 mixture Substances 0.000 description 21
- 229910000027 potassium carbonate Inorganic materials 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 13
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 11
- 238000002329 infrared spectrum Methods 0.000 description 10
- 238000000921 elemental analysis Methods 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- YDFMLJHTEKBSQG-UHFFFAOYSA-N 2,3-dimethoxy-3-(2-methoxyphenyl)prop-2-enoyl chloride Chemical compound COC(C(Cl)=O)=C(OC)C1=CC=CC=C1OC YDFMLJHTEKBSQG-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000000304 vasodilatating effect Effects 0.000 description 2
- GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YIWGJFPJRAEKMK-UHFFFAOYSA-N 1-(2H-benzotriazol-5-yl)-3-methyl-8-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carbonyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione Chemical compound CN1C(=O)N(c2ccc3n[nH]nc3c2)C2(CCN(CC2)C(=O)c2cnc(NCc3cccc(OC(F)(F)F)c3)nc2)C1=O YIWGJFPJRAEKMK-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- LQVXSNNAFNGRAH-QHCPKHFHSA-N BMS-754807 Chemical compound C([C@@]1(C)C(=O)NC=2C=NC(F)=CC=2)CCN1C(=NN1C=CC=C11)N=C1NC(=NN1)C=C1C1CC1 LQVXSNNAFNGRAH-QHCPKHFHSA-N 0.000 description 1
- PAFZNILMFXTMIY-UHFFFAOYSA-N Cyclohexylamine Natural products NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 1
- 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
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- YTFVRYKNXDADBI-UHFFFAOYSA-N O-Methylsinapic acid Natural products COC1=CC(C=CC(O)=O)=CC(OC)=C1OC YTFVRYKNXDADBI-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 102100023185 Transcriptional repressor scratch 1 Human genes 0.000 description 1
- 101710171414 Transcriptional repressor scratch 1 Proteins 0.000 description 1
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000006309 butyl amino group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 125000004915 dibutylamino group Chemical group C(CCC)N(CCCC)* 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 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
- 238000005259 measurement Methods 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- XWINCPYLXQTPQV-UHFFFAOYSA-N piperazine Chemical compound C1CNCCN1.C1CNCCN1 XWINCPYLXQTPQV-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
杢光明i;j強い血管拡張作用を有する新規な1−(6
,4,5−トリメ1′牛シンンナモイル)−4−アミン
カルボニルエチル&&=ビペラノン入ひホモピペラジン
誘導体、及びその薬理学的eごdl−谷しうる酸付加塩
、並びにその製造方法に関するものである。[Detailed description of the invention] Mokkomei i;j A novel 1-(6
, 4,5-Trimethicinnamoyl)-4-aminecarbonylethyl &&=biperanone-containing homopiperazine derivative, its pharmacological acid addition salt, and its production method. .
史tこ註り、 <ぎえば、本発明)J一般式(1ンR2
が炭素数1〜60直鎖状もしくは分枝鎖状のアルキル基
、又は炭素数5〜7のシクロアルキル基であるアミン基
を表わすか、もしくはR1およびR2が同一もしくは異
なって、炭素数1〜乙の直鎖状もしくは分枝鎖状のアル
キル基であるアミ7基を表わすか、もしくはR1とR2
とが一緒になって環状となったアミノ基を表わし、nは
2又は乙の整数を表わす。)
で示される新規な1− (3,4,5−)IJメトキシ
ンンナモイル)−4−アミノカルボニルエチル置換ピペ
ラジン及びホモピペラジン誘導体、及びその薬理学的に
許容しうる酸付加塩、並びにその製造方法eこ関するも
のである。History Notes, <For example, the present invention) J general formula (1-R2
represents an amine group which is a linear or branched alkyl group having 1 to 60 carbon atoms, or a cycloalkyl group having 5 to 7 carbon atoms, or R1 and R2 are the same or different and represent a linear or branched alkyl group having 1 to 60 carbon atoms; represents the amine 7 group which is a straight chain or branched alkyl group of O, or R1 and R2
represents an amino group which is cyclic when taken together, and n represents an integer of 2 or O. ) Novel 1-(3,4,5-)IJmethoxinannamoyl)-4-aminocarbonylethyl-substituted piperazine and homopiperazine derivatives, and their pharmacologically acceptable acid addition salts, and their This relates to the manufacturing method.
これまで数多くの血管拡張剤が開発研究されてきたが、
薬効、副作用等の点に面積々の改善されるべき問題が残
されていた。本願発明者らは血管拡張作用の優れた医薬
品を見い出すべく鋭意研究した結果、前記一般式(1)
で示され)る新規な1−(3,4,5−)リメトキシン
ンナモイル)−4−アミノカルボニルエチル置換ヒベラ
シン及びホモピペラジン誘導体、およびその薬理学的に
許容しつる酸付加塩が、脳、末梢、冠朋管tこおいて優
れた血管拡張作用を有しており、医薬として極めて有利
であることを見い出し本発明tこ到達した。Many vasodilators have been developed and researched, but
There were still many problems that needed to be improved in terms of drug efficacy, side effects, etc. As a result of intensive research to find a drug with excellent vasodilatory action, the inventors of the present application found that the general formula (1)
Novel 1-(3,4,5-)rimethoxine annamoyl)-4-aminocarbonylethyl-substituted hiveracin and homopiperazine derivatives, and their pharmacologically acceptable thallic acid addition salts, It has been found that it has an excellent vasodilatory effect in the periphery and the coronary tract, and is extremely advantageous as a medicine, and the present invention has been achieved.
アミン、フ′ロビルアミノ、インプロピルアミノ。Amines, fluorobylamino, inpropylamino.
ブチルアミ7、イソブチルアミノ、8θC−ブチルアミ
ノ、 tert−ブチルアミノ、ペンチルアミノ、ヘキ
シルアミム シクロへキシルアミノ。Butylamino 7, isobutylamino, 8θC-butylamino, tert-butylamino, pentylamino, hexylamino cyclohexylamino.
ジメチルアミノ、ジエチルアミノ、ジプロピルアミノ、
ジブチルアミノ、ジイソプロピルアミノ、メチルエチル
アミノ、メチルフ゛ロビルアミノ、メナルブチルアミノ
、メチルエチルアミノイル
イミノ基等が挙げられる。dimethylamino, diethylamino, dipropylamino,
Examples include dibutylamino, diisopropylamino, methylethylamino, methylphyllamino, menalbutylamino, and methylethylaminoylimino groups.
本発明の前記一般式(1)で示される化合物は、+1[
望に&C1じて薬理学的1こ許容しうる酸付加塩に変換
することも、又は生成した酸付加塩から塩基を遊離さゼ
ることもできる。The compound represented by the general formula (1) of the present invention has +1 [
If desired, it can be converted into a pharmacologically acceptable acid addition salt, or the base can be liberated from the acid addition salt formed.
本発明の前記一般式(1)で示される化合物の薬理学的
に許容しつる酸付加塩としては、たとえば、塩酸、硝酸
、硫酸、臭化水素酸、ヨウ化水素酸、燐酸等の鉱酸塩、
あるいは、酢酸。Examples of pharmacologically acceptable acid addition salts of the compound represented by the general formula (1) of the present invention include mineral acids such as hydrochloric acid, nitric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, and phosphoric acid. salt,
Or acetic acid.
マレイン#、7マール!、クエン酸、シーウ酸。Malene #, 7 marle! , citric acid, shiulic acid.
自石酸等の有機酸塩が挙げられ、特に好ましい酸付加塩
としてはマレイン酸および7マール酸塩が挙げられる。Examples include organic acid salts such as autolithic acid, and particularly preferred acid addition salts include maleic acid and heptamarate.
本発明の前記一般式(1)で示される新規な1−(3,
4,5−トリメトキシシンナモイル)−4−アミノカル
ざニルエチル置換ピペラジン及びホモピペラジン誘導体
は、以下の様にして製造することができる。The novel 1-(3,
The 4,5-trimethoxycinnamoyl)-4-aminocarzanylethyl-substituted piperazine and homopiperazine derivatives can be produced as follows.
即ち、本発明に係る化合物の製造方法の第一の様式tこ
よれば、@記一般式(1)で示される化合物は、次の一
般式(11)
)
で示される1−アミノカルホ゛ニルエチル置換ピペラジ
ン又はホモピペラジン誘導体と、次の一般式(Ill
)
(式中、Xはハロゲン原子、殊tこクロル又はブロム原
子を表わす。)
で示される3、4.5−)リメトキ7桂皮酸ハロゲニド
とを反応させることにより製造することかできる。That is, according to the first method of the method for producing a compound according to the present invention, the compound represented by the general formula (1) is a 1-aminocarbonylethyl-substituted compound represented by the following general formula (11). Piperazine or homopiperazine derivative and the following general formula (Ill
) (wherein, X represents a halogen atom, especially a chloro or bromine atom).
蒙
本発明の方法の特に好ましい実施〆様は、前記一般式(
■)で示される1−γミノカルネボニルエチル置換ピペ
ラジン又は小モビペラジン誘導体1当飯eこ対して、前
記一般式(Ill )で示される3、4.5−)リメト
キ/桂皮酸ハロゲニドを少なくとも1当蓋以上、好まし
く i;r i、 2〜16当鰍を用いて、無水の不活
性有機溶媒中で反応せしめることである。A particularly preferred implementation of the method of the present invention is based on the general formula (
1) of the 1-γminocarnebonylethyl-substituted piperazine or small mobiperazine derivative represented by (2), and at least one 3,4.5-)rimethoxy/cinnamic acid halide represented by the general formula (Ill). The reaction is carried out in an anhydrous inert organic solvent using 2 to 16 pieces of eel, preferably i;r i.
本発明の方法において使用される不活性有機溶媒として
は、反応を阻害しない限りいかなるものでもよく、たと
えば、アセトン、エーテル。Any inert organic solvent may be used in the method of the present invention as long as it does not inhibit the reaction, such as acetone and ether.
テトラヒドロフラン、ジオキサン、ベンゼン。Tetrahydrofuran, dioxane, benzene.
トルエン、クロロホルム等が使用される。Toluene, chloroform, etc. are used.
又、反応は室温から使用される有機溶媒の加熱還流下に
おいて行われ、特に好ましくは室温下において行うこと
である。Further, the reaction is carried out at room temperature while heating and refluxing the organic solvent used, and is particularly preferably carried out at room temperature.
本発明の製造方法において出発原料となったmE−m式
(II)で示される1−アミノカルホ゛ニルエチル置換
ピペラジン及びホモピペラジン誘導体は、一部を除きい
ずれも新規な物質であり、その製造については参考例に
記載した。The 1-aminocarbonylethyl-substituted piperazine and homopiperazine derivatives represented by mE-m formula (II), which are the starting materials in the production method of the present invention, are all new substances except for a few, and the production thereof is as follows: Described in the reference example.
又、前記一般式(III)で示される3、4.5−トリ
メトキシ桂皮酸ハロゲニドは、3.4゜5− ) IJ
メ)キシ桂皮酸を常法#cvEい酸ノ)IllIゲニ
ドtこ用時変侠することにより製造される。Further, the 3,4,5-trimethoxycinnamic acid halide represented by the general formula (III) is 3.4°5-) IJ
It is produced by converting cicinnamic acid to cvE acid and IllI genide in a conventional manner.
本発明に係る化合物のa造方法の観二の様式によれば、
前記一般式(1)で示される化合物は、次の一般式(1
v)
(式中、n&J前述と同意義を表わす。)で示される1
−(3,4,5−)リメトキシシンナモイル)ヒ′ペ
ラジン又はホモピペラジンと、次の一般式(V)
ロゲン摩子、殊にクロル又はブロム原子を表わす。)
で示されるアミ7カルボニルエチルハライトトを、脱酸
剤としての塩基の存在下1こ反応させることにより製造
することかできる。According to the second aspect of the method for producing a compound according to the present invention,
The compound represented by the general formula (1) is represented by the following general formula (1).
v) 1 represented by (in the formula, n&J represents the same meaning as above)
-(3,4,5-)rimethoxycinnamoyl)hyperazine or homopiperazine and the following general formula (V) represents a rogene atom, in particular a chlor or bromine atom. ) It can be produced by reacting ami7carbonylethyl halide represented by the following in the presence of a base as a deoxidizing agent.
本発明の特をこ好ましい実施態様は、前記一般式(IV
)7’qeすれル1− (3,4,5−ト+)1トキシ
シンナモイル)ピペラジン又はホモピペラジン1当朦に
対して、前記一般式(Y)で示されるアミノカルビニル
エチルハライドを少なくとも1当量以上、好ましくは1
.2〜1.3当量を用いて、無水の不活性有機溶媒中、
脱酸剤としての塩基の少なくとも1当量以上、好ましく
は1.2〜1.3当量の存在下に反応せしめることであ
る。A particularly preferred embodiment of the present invention is the general formula (IV
)7'qeSrel1-(3,4,5-t+)1toxycinnamoyl) per 1 portion of piperazine or homopiperazine, at least an amount of aminocarbinylethyl halide represented by the general formula (Y) is added. 1 equivalent or more, preferably 1
.. in an anhydrous inert organic solvent using 2 to 1.3 equivalents.
The reaction is carried out in the presence of at least 1 equivalent, preferably 1.2 to 1.3 equivalents, of a base as a deoxidizing agent.
本発明の方法において使用される不活性′4Hi機溶媒
としては、反応を阻害しない限りいかなるものでもよく
、たとえば、アセトン、エタノール、エーテル、テトラ
ヒドロフラン、ジAキサン、ベンゼン、トルゴン、クロ
ロホルム等カ使用される。Any inert '4Hi organic solvent may be used in the method of the present invention as long as it does not inhibit the reaction. Ru.
本発明の方法において使用される脱酸剤としての塩基と
しては、たとえば、トリエチルアミン、ピリジン、炭酸
カリウム等が挙げられる。Examples of the base used as a deoxidizing agent in the method of the present invention include triethylamine, pyridine, potassium carbonate, and the like.
又、反応は室温から使用される有機溶媒の加熱還流下に
おいて行われ、特に好ましくは使用される有機溶媒の加
熱還流温度下において行うことである。Further, the reaction is carried out from room temperature under heating to reflux of the organic solvent used, particularly preferably carried out under heating to reflux temperature of the organic solvent used.
本発明の製造方法において出発原料となった前記一般式
(IV)テ示すtt7+i −(3,4、5−トリメト
キシシンナモイル)ピペラジンは、たとえば、特開昭5
2−10282号に既に開示さtている公知の物質であ
り、又1−(3゜4.5−)リメトキシシンナモイル)
ホモピペラジンも、たとえば、特開昭51−82285
号に既に開示されている公知の物質である。The tt7+i-(3,4,5-trimethoxycinnamoyl)piperazine represented by the general formula (IV), which is the starting material in the production method of the present invention, is, for example,
2-10282, and 1-(3°4.5-)rimethoxycinnamoyl)
Homopiperazine is also disclosed in, for example, JP-A-51-82285.
It is a known substance already disclosed in No.
又、FIMr2一般式(V)で示されるアミノカルボニ
ルエチルハライドは、一部を除きいずれも公知の物質で
あり、たとえば、ザ・ジャーナル・オプ・オルガニック
・ケミストリー(The Journalororga
nicahe+nj、5try)、 16+ 1285
(1951))こ記載されているように1.6−クロ
ロ7”ロピオニルクロリドとアミンとを反応させること
1こより製造される。In addition, the aminocarbonylethyl halide represented by FIMr2 general formula (V) is a known substance, with some exceptions; for example, it has been published in The Journal of Organic Chemistry
nicahe+nj, 5try), 16+ 1285
(1951)) by reacting 1,6-chloro7''ropionyl chloride with an amine as described.
尚、前記一般式(1)で示される本願発明化合物の構造
は、核磁気共鳴(NMR)スペクトルおよび赤外線吸収
(工R)スペクトルケこより決定すれている。NMRス
ペクトルは、8不電子px−90Qスペクトロメーター
を用い、内部標準としてテトラメチルシフン(TMS)
を用いて室温にて(但し、1−(3,4,5−)リメト
キシンンナモイル)−4−アミノカルホ。The structure of the compound of the present invention represented by the general formula (1) has been determined from the nuclear magnetic resonance (NMR) spectrum and the infrared absorption (R) spectrum. NMR spectra were performed using an 8-electronless px-90Q spectrometer with tetramethylsiphon (TMS) as an internal standard.
at room temperature using 1-(3,4,5-)rimethoxinannamoyl)-4-aminocarpho.
ニルエチルホモピペラジン誘導体の−Sは50゜にて)
+10定した。工Rスペクトルは日本分光工RA−20
2を用いて測定した。以下実施例において、そのデータ
ーを示すが、その際以下の略号を用いている。8ニ一重
線、d:二重線。-S of nylethylhomopiperazine derivative is at 50°)
It was fixed at +10. The engineering R spectrum is JASCO RA-20.
2 was used for measurement. In the Examples below, the data will be shown, using the following abbreviations. 8 double single line, d: double line.
t:三重線+ q’四重線、86X:六重線、m:多塩
線、brニブロード、工R:赤外線吸収。t: triplet + q' quartet, 86X: sextet, m: polychloride, br nibroad, R: infrared absorption.
以下、不発Iカを実施例によって説明する。Hereinafter, the unexploded IC will be explained using an example.
参考−1
1−(2−(メチルアミ/カルボニルフェチル〕ピペラ
ジン
ビベラジン4.83gのエタノール40s/jl液に、
炭酸カリウム3.90gおよびN−メチル−6−クロロ
プロピオナミド3.41gのエタノール20#/溶液を
〃uえ、26時間加熱還流する。Reference-1 1-(2-(methylamino/carbonylphetyl)piperazine Biverazine 4.83g in ethanol 40s/jl solution,
A solution of 3.90 g of potassium carbonate and 3.41 g of N-methyl-6-chloropropionamide in 20 # of ethanol is added and heated under reflux for 26 hours.
反応後不溶物を炉夫し、溶媒を留去する。残渣を塩酸水
溶液にて酸性となし、クロロホルム洗次
浄し、メいて炭酸カリウムにてアルカリ性となし、再び
クロロホルム洗浄する。水層を炭酸カリウムにて飽和し
、クロロホルム抽出する。クロロホルム層は脱水。溶媒
を留去して、無色結& 3.73 gを得る。After the reaction, insoluble matter is removed from the furnace and the solvent is distilled off. The residue is made acidic with an aqueous hydrochloric acid solution, washed with chloroform, then made alkaline with potassium carbonate, and washed again with chloroform. The aqueous layer was saturated with potassium carbonate and extracted with chloroform. The chloroform layer is dehydrated. The solvent was distilled off to obtain 3.73 g of a colorless solid.
工Rスペクトル ν (KErJ傷−1;3300にN
nハ1650 (−aoN/−)実施例1
1− (3,4,5−)リメトキシシンナモイア
k) −4−(2−<fiチルアミノ力ルボニルノエチ
ル〕ピペラジン
参考例1で侍た1−(2−(メチルアミノカルボニルフ
エチル〕ピペラジン3.50gのクロロホルム50s/
溶液に、室温攪拌下、5.4゜5−トリメトキシ桂皮酸
クロリド6、OOgを加え、室温にて25分間攪拌する
。溶媒を留去し、残渣にベンゼンおよび塩酸水溶液を加
えて振とり。不溶物をP夫し、水層を分取する。水層は
炭酸カリウムにてアルカリ性となし、クロロホルム抽出
する。クロロホルム層は水洗、脱水。Engineering R spectrum ν (KErJ scratch-1; 3300 to N
nha 1650 (-aoN/-) Example 1 1-(3,4,5-)rimethoxycinnamoiak) -4-(2-<fithylaminocarbonylnoethyl]piperazine Reference Example 1 1 -(2-(methylaminocarbonylphethyl)piperazine 3.50g chloroform 50s/
5.4° 5-trimethoxycinnamic acid chloride 6, OOg was added to the solution while stirring at room temperature, and the mixture was stirred at room temperature for 25 minutes. The solvent was distilled off, and benzene and an aqueous hydrochloric acid solution were added to the residue, which was then shaken. Insoluble matter is removed and the aqueous layer is separated. The aqueous layer is made alkaline with potassium carbonate and extracted with chloroform. The chloroform layer was washed with water and dehydrated.
溶媒を留去し、淡黄色結晶4.61gを得る。エタノー
ルから再結晶して、融点182〜185゜の淡黄色針状
晶を得る。The solvent was distilled off to obtain 4.61 g of pale yellow crystals. Recrystallization from ethanol gives pale yellow needles with a melting point of 182-185°.
工Rスペクトル y (KBrJall:3370
()mud、 1655r i 645 (−0ON(
)元素分析値 O2OH29M305
理論i1 o、 61.56;H,7,47iL 1
0.73実験値 0 、61.29 i H,7,66
i M、 10.55参考例2
l−C2−(エチルアミノカルボニルフエチル〕ビペラ
ジン
ビベラジン4.73gのエタノール40s/Ill液に
、炭酸カリウム3.79 gおよびN−エチル−6−ク
ロロプロピオナミド5.72 gのエタ/−ル4011
/溶液を加え、20時間加熱還流する。Engineering R spectrum y (KBrJall:3370
()mud, 1655r i 645 (-0ON(
) Elemental analysis value O2OH29M305 Theory i1 o, 61.56; H,7,47iL 1
0.73 experimental value 0, 61.29 i H, 7,66
i M, 10.55 Reference Example 2 l-C2-(ethylaminocarbonyl ethyl)biperazine To a solution of 40s/Ill of ethanol containing 4.73 g of viperazine, 3.79 g of potassium carbonate and N-ethyl-6-chloro Propionamide 5.72 g ethanol 4011
/ solution and heated under reflux for 20 hours.
以下、参考例1と同様に処理し、淡黄色液体6゜75g
を得る。The following process was carried out in the same manner as in Reference Example 1, and 6°75g of pale yellow liquid was obtained.
get.
工Rスペクトル ν (filll J眞−1:350
0 (、、ia〕r 1640 <−aoN’:
、)実施例2
1− <5.4.5−トリメトキシシンナモイルJ −
4−(2−(エチルアミツカ/I/d?ニルノエチル〕
ピペラジン
参考例2で得た1−(2−(エチルアミノ力ルボニルン
エチル〕ピペラジン3.55gのクロロホルム40s/
溶液に、室温攪拌下、5,4゜5−トリメトキシ桂皮酸
クロリド5.66 gを加え、室温にて60分間攪拌す
る。以下、実施例1と同様に処理して、淡黄色結晶5.
80gを得る。酢酸エチルエステルから再結晶して、融
点151〜152°の淡黄色針状晶を得る。Engineering R spectrum ν (fill J-1:350
0 (,,ia]r 1640 <-aoN':
,) Example 2 1-<5.4.5-trimethoxycinnamoyl J-
4-(2-(ethylamizuka/I/d?nilnoethyl)
Piperazine 3.55 g of 1-(2-(ethylaminorubonylene ethyl)piperazine obtained in Reference Example 2) in chloroform 40 s/
5.66 g of 5,4°5-trimethoxycinnamic acid chloride was added to the solution while stirring at room temperature, and the mixture was stirred at room temperature for 60 minutes. Thereafter, the same treatment as in Example 1 was carried out to obtain light yellow crystals.
Obtain 80g. Recrystallization from ethyl acetate gives pale yellow needles with a melting point of 151-152°.
工Rスペクトル ν (KBrJ億−1=510 C
’:yu)+ 1625+ 1650 (−ooM4
)元素分析値 021H31N305
理論値 OI 62.20 ; 1117.71111
0.36実験値 0162.24;L 7.86;M、
10.58参考例5
l−(2−(プロピルアミノカルボニルフエチル〕ピペ
ラジン
ピペラジン5.75gのベンゼン60s/懸濁液に、ト
リエチルアミン6、75 gおよびN−プロプ
ビル−6−クロロプロピオナミド5.00gのベンゼン
60s/溶液を加え、20時間加熱還流する。反応後不
溶物をP夫し、溶媒を留去する。Engineering R spectrum ν (KBrJ billion-1=510 C
':yu)+1625+1650 (-ooM4
) Elemental analysis value 021H31N305 Theoretical value OI 62.20; 1117.71111
0.36 experimental value 0162.24;L 7.86;M,
10.58 Reference Example 5 1-(2-(Propylaminocarbonylphethyl)piperazineTo a suspension of 5.75 g of piperazine in 60 s of benzene, 6.75 g of triethylamine and 5.75 g of N-probuvil-6-chloropropionamide were added. Add 00g of benzene 60s/solution and heat under reflux for 20 hours.After the reaction, insoluble matter is removed and the solvent is distilled off.
残渣を塩酸水溶液にて酸性となし、酢酸エチルエステル
洗浄し、次いで炭酸カリウムにてアルロホルム抽出する
。クロロホルム層は脱水。溶媒を貿夫し、淡黄色液体6
.50g′4t4る。The residue was made acidic with an aqueous hydrochloric acid solution, washed with ethyl acetate, and then extracted with potassium carbonate in alloform. The chloroform layer is dehydrated. Remove the solvent, pale yellow liquid 6
.. 50g'4t4ru.
工Rスペクトル ν (film )画−l:3300
(ンNHJ、1640 (−aom/−〕実施例3
1− (3,4,5−トリメトキシシンナモイルJ−4
−〔2−(プロピルアミ/カルボニルフエチル〕ピペラ
ジン
参考例6で得た1−(2−(プロピルアミ/カルポニル
フエチル〕ピペラジン6.50gのクロロホルム50−
溶液に、室温攪拌下、3,4゜5−トリメトキシ桂皮酸
クロリド10.05gをDOえ、室温にて25分間攪拌
する。以下、実施例1と同様に処理して、淡黄色結晶7
.71gを得る。酢酸エチルエステルから再結晶して、
融点129〜163°の無色板状晶を得る。Engineering R spectrum ν (film) image-l: 3300
(NHJ, 1640 (-aom/-) Example 3 1- (3,4,5-trimethoxycinnamoyl J-4
- [2-(Propylami/Carbonyl Phethyl] Piperazine 6.50 g of 1-(2-(Propylami/Carponyl Phethyl) Piperazine obtained in Reference Example 6) in chloroform 50-
10.05 g of 3,4°5-trimethoxycinnamic acid chloride was added to the solution while stirring at room temperature, and the mixture was stirred at room temperature for 25 minutes. Hereafter, the same treatment as in Example 1 was carried out to obtain pale yellow crystal 7.
.. Obtain 71g. Recrystallized from ethyl acetate,
Colorless platelet crystals with a melting point of 129-163° are obtained.
IRスペクトル y (film )m l:り34
0 <>NH)、1640.1660 (−ooy<)
元素分析値 022H33N305
理論値 01 62.99 ; H,7,95i N、
10.02実験値 0. 62.98;Hz 8.0
6;IJ、 10.07参考例4
l−(2−(イソブ四ピルアミ/カルゲニル2エチル〕
ピペラジン
ピペラジン1.84gのベンゼン30m/mli液に、
トリエチルアミン2.16gおよびN−イソプロピル−
6−クロロプロビオナミド1.60gのベンゼン2〇−
溶液を加え、24時間加熱還流する。反応後不溶物を−
失し、溶媒を留去する。残渣にエーテルを加え不溶物を
炉夫し、P液は脱水。溶媒を留去し、得られた残渣を蒸
留して、沸点150〜153° (3,5■HgJの無
色液体0.96gを得る。IR spectrum y (film) ml: ri34
0 <>NH), 1640.1660 (-ooy<)
Elemental analysis value 022H33N305 Theoretical value 01 62.99; H,7,95i N,
10.02 Experimental value 0. 62.98;Hz 8.0
6; IJ, 10.07 Reference example 4 l-(2-(isobutetetyrami/cargenyl 2-ethyl)
Piperazine Piperazine 1.84g in benzene 30m/ml solution,
2.16 g of triethylamine and N-isopropyl-
6-chloroprobionamide 1.60 g benzene 20-
Add the solution and heat to reflux for 24 hours. After the reaction, remove the insoluble matter.
The solvent is distilled off. Ether is added to the residue to remove insoluble matter, and the P liquid is dehydrated. The solvent was distilled off, and the resulting residue was distilled to obtain 0.96 g of a colorless liquid with a boiling point of 150-153° (3.5 μHgJ).
工Rスペクトル ν (film )ex l:330
0 (>NHJ、1640 (−0ONぐ〕実に例4
1− (3,4,、5−トリメトキシシンナモイル)−
4−(2−(イソプロピルアミ/lJルiニルフエチル
〕ピペラジン
さ考例4で得た1−(2−(イソプロピルアミノカルポ
ニルフエチル〕ピペラジン5.00gのクロロホルム1
00s/溶液に、室温攪拌下、5.4.5−トリメトキ
シ桂皮酸クロリド7.76gを加え、室温にて20分間
攪拌する。以下、実施例1と同様に処理して、淡黄色結
晶1o、27gを得る。酢酸エチルエステルから再結晶
して、融点97〜98°の無色板状晶を得る。Engineering R spectrum ν (film)ex l:330
0 (>NHJ, 1640 (-0ONgu) Example 4 1- (3,4,,5-trimethoxycinnamoyl)-
5.00 g of 1-(2-(isopropylaminocarponyl phethyl)piperazine obtained in Example 4) in chloroform 1
7.76 g of 5.4.5-trimethoxycinnamic acid chloride is added to the 00s/solution while stirring at room temperature, and the mixture is stirred at room temperature for 20 minutes. Thereafter, the same treatment as in Example 1 was carried out to obtain 27 g of pale yellow crystals. Recrystallization from ethyl acetate gives colorless platelets with a melting point of 97-98°.
工Rスペクトル ν (KBr )儒−1:3280
(ンNHJ、1645 (−0ONζ〕参考例5
l−(2−(フチルアミノカルボニルJエチル〕ピペラ
ジン
ピペラジン5.78gのベンゼン50s(懸m液に、ト
リエチルアミン6.79gおよびN−ブチル−6−クロ
ロプロピオナミド5.50gのベンゼン40g/溶液を
加え、26時間加熱還流する。Engineering R spectrum ν (KBr) Confucian-1:3280
(NHJ, 1645 (-0ONζ) Reference Example 5 l-(2-(phthylaminocarbonylJethyl)piperazine) 5.78 g of piperazine was suspended in a solution of 50 s of benzene, 6.79 g of triethylamine and N-butyl-6- A solution of 5.50 g of chloropropionamide in 40 g of benzene is added and heated under reflux for 26 hours.
反応後不溶物をF去し、溶媒を留去する。残渣な塩酸水
溶液にて酸性と7zL、酢酸エチルエステル洗浄し、次
いで炭酸カリウムにてアルカリ性となし、再びエーテル
洗浄する。水層な炭酸カリウムにて飽和只1、クロロホ
ルム抽出する。After the reaction, insoluble matter is removed by F and the solvent is distilled off. The residue was acidified with an aqueous hydrochloric acid solution and washed with ethyl acetate for 7 mL, then made alkaline with potassium carbonate, and washed with ether again. The aqueous layer was saturated with potassium carbonate and extracted with chloroform.
クロロホルム層は脱水。溶媒を留去して、淡黄色液体6
.90gを得る。The chloroform layer is dehydrated. Distill the solvent to obtain pale yellow liquid 6.
.. Obtain 90g.
工Rスペクトル ν (film )m 1:3300
<:zNH)+ 1640 <−ooy/−を実施例
5
1− (3,4,5−トリメトキシシンナモイルJ −
4−(2−(ブチルアミ7カルボニルフエチル〕ピペラ
ジン
参考例5で得た1−(2−(ブチルアミ7カルボニルフ
エチル〕ピペラジン7.10gのクロロホルム601B
/溶液に、室温攪拌下、3.4゜5−トリメトキシ桂皮
酸クロリド10.30gを加え、室温にて15分間攪拌
する。以下、実施例1と同一に処理して、淡黄色結晶1
1.00gを得る。エタノールから再幀晶して、融点1
52.5〜1335°の無色板状晶ヲ得る。Engineering R spectrum ν (film)m 1:3300
<:zNH)+ 1640 <-ooy/- Example 5 1-(3,4,5-trimethoxycinnamoyl J-
Chloroform 601B of 7.10 g of 1-(2-(butylamino7carbonyl ethyl)piperazine obtained in Reference Example 5)
10.30 g of 3.4° 5-trimethoxycinnamic acid chloride was added to the solution while stirring at room temperature, and the mixture was stirred at room temperature for 15 minutes. Hereinafter, the same process as in Example 1 was carried out to obtain pale yellow crystal 1.
Obtain 1.00g. Recrystallized from ethanol, melting point 1
Colorless plate crystals with an angle of 52.5 to 1335° are obtained.
IRスペクトk w (KBrJcm ’:335
0 (>NH)、1 640. 1 660 (−
〇〇Nく)元素分析値 023835N305
理論値 0 、63.72 ; H,8,14i N、
9.69実験値 0 、 63.81 il(、8,
29;h+ 9.72絡考例6
1−〔2−(イソブチルアミ7カルボニルノエチル〕ピ
ペラジン
ピペラジン16.80gのベンゼン100sl!M濁故
に、トリエチルアミン19.70gおよびN−インブチ
ル−3−クロロプロピオナミド16゜00gのベンゼン
100−溶液を加え、21時間加熱還流する。以下、参
考例6と同様に処理して、淡黄色液体11.50gを得
る。IR spectrum k w (KBrJcm': 335
0 (>NH), 1 640. 1 660 (-
〇〇Nku) Elemental analysis value 023835N305 Theoretical value 0,63.72; H,8,14i N,
9.69 experimental value 0, 63.81 il(,8,
29;h+ 9.72 Concerning Example 6 1-[2-(Isobutylami7carbonylnoethyl]piperazine100sl!M of benzene containing 16.80g of piperazine was cloudy, so 19.70g of triethylamine and N-inbutyl-3-chloropropiona A benzene 100-solution containing 16.00 g of amide was added, and the mixture was heated under reflux for 21 hours.Then the mixture was treated in the same manner as in Reference Example 6 to obtain 11.50 g of a pale yellow liquid.
工Rスペクトル ν (filmJcml:5500
(ンMHJ、1640 (−0ON< )実施例
6
l−(3,4,5−トリメトキシシンナモイル)−4−
(2−(イソブチルアミ7カルボニルノエチル〕ピペラ
ジン
参考例6で得た1−(:2−(イソブチルアミ7カルボ
ニルノエチル〕ピペラジン7、 OOgのクロロホルム
1501溶液に、室温攪拌下、5゜4.5−)リメトキ
シ桂皮酸クロリド10.15gを加え、室温にて15分
間攪拌する。以下、実施例1と同様に処理し、淡褐色液
体13.80gを得る。Engineering R spectrum ν (filmJcml:5500
(MHJ, 1640 (-0ON< ) Example 6 l-(3,4,5-trimethoxycinnamoyl)-4-
(2-(isobutylami7carbonylnoethyl)piperazine1-(:2-(isobutylami7carbonylnoethyl)piperazine 7 obtained in Reference Example 6) was added to a solution of OOg in chloroform 1501 under stirring at room temperature for 5°4. 5-) Add 10.15 g of rimethoxycinnamic acid chloride and stir at room temperature for 15 minutes.Then, the same procedure as in Example 1 is carried out to obtain 13.80 g of light brown liquid.
IRスペクトル y (film )am l:33
20 <;NH)、1640 (−oomぐJ参考例
7
1(2−(sea−ブチルアミ7カル叡二ルフエチル〕
ピペラジン
ピペラジン5.78 gのベンゼン501懸濁液に、ト
リエチルアミ/l)、79gおよびN −(sea−ブ
チルノー6−クロロブロビオナミド5.50gのベンゼ
ン401溶液を加え、23.5時間加熱還流する。反応
後不溶物を−失し、溶媒を留去する。残渣を塩酸水溶液
にて酸性となし、酢酸エチルエステル洗浄し、次いで炭
酸カリウムにてアルカリ性となし、再び酢酸エチルエス
テル洗浄する。水層を炭酸カリウムにて飽相し、クロロ
ホルム抽出する。クロロホルムJll ハ脱水。IR spectrum y (film)am l:33
20 <; NH), 1640 (-oomguJ Reference Example 7 1 (2-(sea-butyramid 7carenyl ethyl)
PiperazineTo a suspension of 5.78 g of piperazine in benzene 501, a solution of 79 g of triethylamine/l) and 5.50 g of N-(sea-butylno-6-chlorobrobionamide) in benzene 401 was added and heated for 23.5 hours. Reflux. After the reaction, insoluble matter is lost and the solvent is distilled off. The residue is made acidic with an aqueous hydrochloric acid solution, washed with ethyl acetate, then made alkaline with potassium carbonate, and washed again with ethyl acetate. The aqueous layer was saturated with potassium carbonate and extracted with chloroform. Dehydrated with chloroform.
溶媒を留去して、淡黄色結晶5.90gを得る。The solvent was distilled off to obtain 5.90 g of pale yellow crystals.
工Rスペクトル v (KBr)crnl:3500
(ンN1(J 、 1 640 (−oON
/−]実施例7
1− <5.4. 5−)リメトキシシンナモイル)
−4−(2−(see−ブチルアミ7カルボニルノエチ
ル〕ピペラジン
参考例7で得た1−(2−(sec−ブチルアミ7カル
ボニルノエチル〕ピペラジン5.80gのクロロホルム
50w/溶液に、室温攪拌下、6゜4.5−)リメトキ
シ桂皮酸クロリド8.40gを加え、室温にて40分間
攪拌する。以下、実施例1と同様に処理し、淡黄色結晶
9.00gを得る。酢酸エチルエステルから再結晶して
、融点78〜80°の無色針状晶を得る。Engineering R spectrum v (KBr) crnl:3500
(N1(J, 1 640 (-oON
/-] Example 7 1- <5.4. 5-) Rimethoxycinnamoyl)
-4-(2-(see-butylamino7carbonylnoethyl)piperazineTo a solution of 5.80 g of 1-(2-(sec-butylamino7carbonylnoethyl)piperazine) obtained in Reference Example 7 in 50 w/chloroform was stirred at room temperature. , 6゜4.5-) 8.40 g of rimethoxycinnamic acid chloride is added and stirred at room temperature for 40 minutes. The following procedure is carried out in the same manner as in Example 1 to obtain 9.00 g of pale yellow crystals. From ethyl acetate. Recrystallization gives colorless needles with a melting point of 78-80°.
工Rスペクトル ν (KBrJ譚−1=3270 <
>wH* 、 1640 (−c6w<−を参考例8
1(2−(teri−ブチルアミ7カルボニルンエチル
〕ピペラジン
ピペラジン21.10gのベンゼン100sl/懸+1
ii液に、トリエチルアミン24.80gおよびN−(
tert−ブチルJ −3−クロロプロピオナミド20
.00gのベン421001g/溶液をD口え、17時
間加熱還流する。以下、参考例5と同様に処理し、淡黄
色結晶18.50gを得る。Engineering R spectrum ν (KBrJ Tan-1=3270 <
>wH*, 1640 (-c6w<-Reference Example 8
24.80 g of triethylamine and N-(
tert-butyl J-3-chloropropionamide 20
.. Pour 00g of Ben 421001g/solution into D mouth and heat under reflux for 17 hours. Thereafter, the same treatment as in Reference Example 5 was carried out to obtain 18.50 g of pale yellow crystals.
工Rスペクトル ν (KEr ) am l:350
0 <>mH)+ 1640 (−ooN<)実施例8
1− (3,4,5−1リメトキシシンナモイル)
4 (2(tert−ブチルアミ/カルメニルJエ
チル〕ピペラジン
誉考例8で得た1−(’l −(tert−ブチルアミ
ノカルボニルλエチル〕ヒ゛ペラジン10.QOgのク
ロロホルム1501溶液に、室温攪拌下、3.4.5−
)リメトキシ桂皮喰クロリド14゜50gkuuえ、室
温にて15分間攪拌する。反1+5後溶媒を留去し、残
渣にベンゼンおよび塩酸水溶液を1](1えて振とう。Engineering R spectrum ν (KEr) am l:350
0 <>mH) + 1640 (-ooN<) Example 8 1- (3,4,5-1 rimethoxycinnamoyl)
4 (2(tert-Butylamino/carmenylJ ethyl)piperazine) To a solution of 10.QOg of 1-('l-(tert-butylaminocarbonyl λ ethyl)hyperazine) obtained in Honorary Example 8 in 1501 chloroform was added 3. .4.5-
) Add 14.50 g of rimethoxycinnamic chloride and stir at room temperature for 15 minutes. After 1+5 incubation, the solvent was distilled off, and the residue was mixed with benzene and an aqueous hydrochloric acid solution for 1 hour and shaken.
析出結晶をデ収し、ろ液の水層を分取する。水層は水噌
化ナトリウム水溶液にてアルカリ注とζし、クロロホル
ム抽出する。先の析出結晶は、水酸化す) 13ウム水
溶液およびクロロホルムの混液中へ加えて振とう。クロ
ロホルム層2分取し、先のクロロホルム抽出液を甘し、
水洗、脱水。溶媒を留去し、黄褐色液体19.54gを
得る。−
IRスペクトル y (fi1m+ ) cm l:
55ろ0 (ンNH)、1645 (−ooug)参考
例9
l−(2−(ペンチルアミノカルボニルJエチル〕ピペ
ラジン
ピペラジン4.46gのベンゼン50m/懸濁液に、ト
リエチルアミン5.23gおよびy−ペンfiv−3−
クロロプロピオナミド4.60gのベンゼン40Il/
溶液を加え、19時間加熱還流する。以下、参考例5と
同様に処理し、黄色液体5.05gを得る。Collect the precipitated crystals and separate the aqueous layer of the filtrate. The aqueous layer is alkalised with an aqueous sodium chloride solution and extracted with chloroform. The precipitated crystals are added to a mixture of 13 um aqueous solution and chloroform and shaken. Take two portions of the chloroform layer, sweeten the chloroform extract,
Washing and dehydration. The solvent was distilled off to obtain 19.54 g of a yellowish brown liquid. - IR spectrum y (fi1m+) cm l:
55 filtration 0 (NH), 1645 (-ooug) Reference Example 9 1-(2-(PentylaminocarbonylJethyl)piperazineTo a suspension of 4.46 g of piperazine in 50 m of benzene, 5.23 g of triethylamine and Y-pen fiv-3-
Chloropropionamide 4.60g benzene 40Il/
Add the solution and heat to reflux for 19 hours. Thereafter, the same procedure as in Reference Example 5 was carried out to obtain 5.05 g of a yellow liquid.
工Rスペクトル y (filmJm 1:330
0 (〉Nn J 、1640 (−aoy<2実
施例9
1−1.4.5−)リメトキシシンナモイルJ−4−(
2−(ペンチルアミノカルボニル)エチルコピペラジン
参考例9で得た1−(2−(ベンチルアミノカルポニル
ンエチル□〕ピペラジン4.55gのクロロホルム60
gtMl液に、室温攪拌下、5.4゜5−トリメトキシ
桂皮酸クロリド6.16gを加え、室温にて15分間攪
拌する。以下、実施例1と同様に処理し、淡黄色結晶7
.14g′4t?lる。Engineering R spectrum y (filmJm 1:330
0 (〉Nn J , 1640 (-aoy<2 Example 9 1-1.4.5-) Rimethoxycinnamoyl J-4-(
2-(pentylaminocarbonyl)ethylcopiperazine 4.55 g of 1-(2-(bentylaminocarbonyl)piperazine obtained in Reference Example 9) in chloroform 60
6.16 g of 5.4° 5-trimethoxycinnamic acid chloride is added to the gtMl solution while stirring at room temperature, and the mixture is stirred at room temperature for 15 minutes. Thereafter, the same treatment as in Example 1 was carried out, and pale yellow crystal 7
.. 14g'4t? Ill.
酢酸エチルエステルから再結晶して、融点75〜77°
の無色板状晶を得る。Recrystallized from ethyl acetate, melting point 75-77°
Obtain colorless plate crystals.
工Rスペクトル ν (KBrJ譚−1=6280
(>MHJl 1640,1660 (OONく]元
素分析値 024”37N305
理論値 a 、 64.41 ;H,8,33;n+
9゜39実験値 0 、64.06;H,8,61iB
i、 9.19参考例10
1−(2−(ヘキシルアミ、7カルボニルJエチル〕ピ
ペラジン
ピペラジン4.94gに、トリエチルアミン5゜80g
8よひN−へキシル−6−クロロプロピオナミド5.5
0gのベンゼン90−溶液を加え、26時間加熱還流す
る。以下、参考例5と同僚に処理し、黄色液体6.00
g1得る。Engineering R spectrum ν (KBrJtan-1=6280
(>MHJl 1640,1660 (OONku) Elemental analysis value 024"37N305 Theoretical value a, 64.41; H, 8, 33; n+
9°39 Experimental value 0,64.06;H,8,61iB
i, 9.19 Reference Example 10 1-(2-(hexylamine, 7 carbonyl J ethyl) piperazine To 4.94 g of piperazine, 5.80 g of triethylamine
8yo N-hexyl-6-chloropropionamide 5.5
Add 0 g of benzene 90-solution and heat to reflux for 26 hours. Below, reference example 5 and colleagues treated, yellow liquid 6.00
Get g1.
IRスペクトル l’ (fllm ) m l:5
500 (>NHJI 1640 (−001J
(J実施例10
1− (!l、 4. 5−)リメトキシシンナモイ
ルJ−4−(2−(ヘキシルアミノ力ルビニルフエチル
〕ピペラジン
s前例ioで得た1−(2−(ヘキシルアミ7カルボニ
ルノエチル〕ピペラジン5.80gのクロロホルム50
m/溶液に、室温攪拌下、3゜4.5−)リメトキシ桂
皮酸りロリド乙40gを加え、室温にて10分間攪拌す
る。溶媒を留去し、残渣にベンゼンおよび塩酸水溶液を
加えて振とう。析出結晶なP取し、クロロホルムに溶解
する。クロロホルム層は水酸化ナトリウム水溶゛液で洗
浄、水洗、脱水。溶媒を留去し、淡黄色結晶8.55g
を得る。酢酸エチルエステルから再結晶して、融点64
〜66°の無色針状晶を得る。IR spectrum l' (fllm) m l:5
500 (>NHJI 1640 (-001J
(J Example 10 1-(!l, 4. 5-)rimethoxycinnamoyl ethyl]piperazine 5.80g chloroform 50
40 g of 3°4.5-)rimethoxycinnamic acid chloride Otsu is added to the m/solution under stirring at room temperature, and the mixture is stirred at room temperature for 10 minutes. The solvent was distilled off, benzene and an aqueous hydrochloric acid solution were added to the residue, and the mixture was shaken. The precipitated crystals of P are collected and dissolved in chloroform. The chloroform layer was washed with an aqueous sodium hydroxide solution, washed with water, and dehydrated. The solvent was distilled off and 8.55 g of pale yellow crystals were obtained.
get. Recrystallized from ethyl acetate, melting point 64.
Colorless needles of ~66° are obtained.
工Rスペクトル y (KBrJ C1l ’:6
290 (>Na)、1640 (−ooM<)参考例
11
1−El−(シクロヘキシルアミ7カルポニルノエナル
〕ピペラジン
ピペラジン4.09gのベンゼン50 g/懸ff1d
に、トリエチルアミン4.80gおよびN−シクロヘキ
シル−6−クロロプロピオナミド4.50gのベンゼン
40s/溶液を加え、23時間加熱還流する。反応後不
溶物を1夫し、溶媒を留去する。残渣を#i曖氷水溶液
て酸性となし、クロロホルム洗浄し、次いで炭酸カリウ
ムにてアルカリ性となし、析出物をデ失する。rp液を
炭酸カリウムにて飽和し、クロロホルム抽出する。Engineering R spectrum y (KBrJ C1l':6
290 (>Na), 1640 (-ooM<) Reference Example 11 1-El-(cyclohexylami7carponylnoenal)piperazine Piperazine 4.09g benzene 50g/suspensionff1d
A solution of 4.80 g of triethylamine and 4.50 g of N-cyclohexyl-6-chloropropionamide in 40 s of benzene was added to the mixture, and the mixture was heated under reflux for 23 hours. After the reaction, insoluble matter was removed and the solvent was distilled off. The residue is made acidic with a #i ice-water solution, washed with chloroform, and then made alkaline with potassium carbonate to remove the precipitate. The RP solution is saturated with potassium carbonate and extracted with chloroform.
クロロホルム層は脱水。溶媒を留去し、淡黄色結晶5.
21g7に:4る。The chloroform layer is dehydrated. The solvent was distilled off and pale yellow crystals were obtained.5.
21g7:4ru.
IRスペクトル y (KBrJ csr l:3
310 (’NH)、1640 (−aouく)実施例
11
1− (3,4,5−トリメトキシシンナ°モイル)−
4−(2−(シクロヘキシルアミ7カルボニルンエチル
〕ピペラジン
参考例11で得た1−(2−(シクロヘキシルアミ7カ
ルボニルンエチル〕ピペラジン5.00gのクロロホル
ム5〇−溶液に、室温攪拌下、3.4.5−トリメトキ
シ桂皮酸クロリド6.43gを加え、室温にて15分間
攪拌する。以下、実施例1と同様に処理し、淡黄色結晶
5.74 gを得る。酢酸エチルエステルから再結晶し
て、融点89〜90,5°の無色針状晶を得る。IR spectrum y (KBrJ csr l:3
310 ('NH), 1640 (-aou) Example 11 1- (3,4,5-trimethoxycinnamoyl)-
4-(2-(cyclohexylami7carbonylonethyl)piperazineTo a solution of 5.00 g of 1-(2-(cyclohexylami7carbonylonethyl)piperazine) obtained in Reference Example 11 in 50% chloroform was added 3. .4. Add 6.43 g of 5-trimethoxycinnamic acid chloride and stir at room temperature for 15 minutes.Proceed in the same manner as in Example 1 to obtain 5.74 g of pale yellow crystals.Recrystallize from ethyl acetate. Colorless needle crystals with a melting point of 89-90.5° are obtained.
工Rスペクトル ν (KBr ) am ’:52q
o <;Nu J、1635 <−001ぐJ参考的1
2
1−(2−(ジメチルアミノカルボニルフエチル)ピペ
ラジン
ピペラジン4.45gに、トリエチルアミン5゜22g
およびN、N−ジメチル−3−りpロプロビオナミド3
.50gのベンゼン90sJM液を加え、23時間加熱
還流する。以下、参考例6と同様に処理し、淡黄色液体
5.15gを得る。Engineering R spectrum ν (KBr) am': 52q
o <;Nu J, 1635 <-001gJ reference 1
2 1-(2-(dimethylaminocarbonylphethyl)piperazineTo 4.45 g of piperazine, 5°22 g of triethylamine
and N,N-dimethyl-3-diproprobionamide 3
.. Add 50 g of benzene 90s JM solution and heat under reflux for 23 hours. Thereafter, the same treatment as in Reference Example 6 was carried out to obtain 5.15 g of a pale yellow liquid.
1Bスペクトル ν (film ) cm ’:52
80 にNoノ、1625 (−coNく)実施例
12
1− (3,4,5−)リメトキシシンナモイ。1B spectrum ν (film) cm': 52
80 No, 1625 (-coN) Example 12 1-(3,4,5-)rimethoxycinnamoy.
ルJ−4−(2−(ジエチルアミノカルビニル1エチル
〕ピペラジン
参考例12で得た1−1:2−(ジメチルアミ/カルボ
ニルJエチル〕ピペラジン2.90g1クロロホルム4
01溶液に、室温攪拌下、5゜4.5−トリメトキシ桂
皮酸クロリド4.82 gを加え、室温にて15分間攪
拌する。以下、実 。2.90 g of 2-(dimethylaminocarbinyl J-ethyl)piperazine obtained in Reference Example 12
4.82 g of 5°4.5-trimethoxycinnamic acid chloride was added to the 01 solution while stirring at room temperature, and the mixture was stirred at room temperature for 15 minutes. The following is the fruit.
施例1と同様に処理し、淡黄色結晶4.22gを得る。The same procedure as in Example 1 was carried out to obtain 4.22 g of pale yellow crystals.
酢酸エチルエステルから再結晶して、融点121〜12
2°の淡黄色針状晶を慢る。Recrystallized from ethyl acetate, melting point 121-12
It has 2° pale yellow needle-like crystals.
工Rスペクトル ν (KBrJ彌−1:1640
(−0ONぐ〕
元素分析値 021H31N305
理論値 0162.20 i)(、7,71;lj、
10.56実験値 0.62.24iH,7−80;L
10.17参考例13
1−(2−(ジエチルアミノカルビニル1エチル〕ピペ
ラジン
ピペラジン5.78gに、トリエチルアミン6゜80g
およびN、M−ジエチル−3−クロロブ例7と同様に処
理し、黄色液体5.78gを得る。Engineering R spectrum ν (KBrJ Ya-1:1640
(-0ONgu) Elemental analysis value 021H31N305 Theoretical value 0162.20 i) (, 7, 71; lj,
10.56 Experimental value 0.62.24iH, 7-80;L
10.17 Reference Example 13 1-(2-(diethylaminocarvinyl 1-ethyl)piperazine To 5.78 g of piperazine, 6°80 g of triethylamine
and N,M-diethyl-3-chlorobute in the same manner as in Example 7 to obtain 5.78 g of a yellow liquid.
工Rスペクトル y (film)cm 1:33
10 (>Nat、1630 (−aomくt実施例1
6
1−(5,4,5−)リメトキシシンナモイルJ−4−
(2−(ジエチルアミノカルビニル1エチル〕ピペラジ
ン
参考例13で得た1−(2−(ジエチルアミノカルビニ
ル1エチル〕ピペラジン5.60gのクロロホルム50
−溶液に、室温攪拌下、3゜4.5−)リメトキシ桂皮
酸クロリド8.09 gを加え、室温にて20分間攪拌
する。以下、実施19111と同様に処理し、黄褐色液
体9.60gを優る。Engineering R spectrum y (film) cm 1:33
10 (>Nat, 1630 (-aomkutExample 1
6 1-(5,4,5-)rimethoxycinnamoyl J-4-
(5.60 g of 1-(2-(diethylaminocarvinyl 1-ethyl)piperazine) obtained in Reference Example 13 in chloroform 50
- Add 8.09 g of 3°4.5-)rimethoxycinnamic acid chloride to the solution while stirring at room temperature, and stir at room temperature for 20 minutes. Hereinafter, the same treatment as in Example 19111 was carried out, and 9.60 g of the yellow-brown liquid was obtained.
工Rスペクトル ’ (fil、m ) cIR−1
゜1640 (’−rjoy4 )
参考例14
1−(2−(ジプロピルアミノカルCニルノエチル〕ピ
ペラジン
ピペラジン5.39gに、トリエチルアミン6、−33
gおよびN、N−ジプロピル−3−10ロブロピオナ
ミド600gのベンゼン100■l溶液を加え、23時
間加熱a流する。以下、参考例7と同様に処理し1黄色
液体5.1’6gを得る。Engineering R spectrum' (fil, m) cIR-1
゜1640 ('-rjoy4) Reference Example 14 1-(2-(dipropylaminocar-C-nylnoethyl)piperazine To 5.39 g of piperazine, triethylamine 6, -33
A solution of 600 g of N,N-dipropyl-3-10 lobropionamide in 100 μl of benzene was added and heated for 23 hours. Thereafter, the same procedure as in Reference Example 7 was carried out to obtain 5.1'6 g of 1 yellow liquid.
工Rスペクトル ν (film )国−1:33”1
0(>NHハ1630 (−aoN<)実施例14
1− (3”、 4. 5−)リメトキシシンナモイル
J−4−L:2−(ジプロピルアミ/カルホ゛二ルノエ
チル〕ピペラジン
浴考例14で得た1−C2−(ジプロピルアミ/カルホ
ニルJエチル〕ピペラジン4.80gのクロロホルム5
0m溶液に、室温攪拌F16゜4.5−トリメトキシ桂
皮酸クロリド6.12gを加え、室温にて15分間攪拌
する。溶媒を留去し、残渣にベンゼンおよび塩酸水溶液
を加えて振とう。水層は炭酸′カリウムにてアルカリ性
となし、クロロホルム抽出する。クロルホルム層は水洗
、脱水。溶媒を留去し、黄色液体8.98gを得る。Engineering R spectrum ν (film) country-1:33”1
0(>NHHa1630 (-aoN<)Example 14 1-(3", 4.5-)rimethoxycinnamoyl J-4-L: 2-(dipropylami/carbonylnoethyl)piperazine bath Example 14 4.80 g of the obtained 1-C2-(dipropylami/carbonyl J ethyl)piperazine in chloroform 5
Add 6.12 g of room temperature stirring F16° 4.5-trimethoxycinnamic acid chloride to the 0m solution and stir at room temperature for 15 minutes. The solvent was distilled off, benzene and an aqueous hydrochloric acid solution were added to the residue, and the mixture was shaken. The aqueous layer was made alkaline with potassium carbonate and extracted with chloroform. The chloroform layer was washed with water and dehydrated. The solvent was distilled off to obtain 8.98 g of a yellow liquid.
工Rスペクトル y (filmJ elm−1:1
640 (−coyぐ〕
参考例15
1−(2−(ピペリジ7カルボニルJエチル〕ピペラジ
ン
ピペラジン3.73gのベンゼン5〇−懸濁液に、トリ
エチルアミン4.38gおよびN−(6−クロロブロビ
オニルノ ピロリジン5.50gのベンゼン10−溶液
を2111え、19時間加熱還流する。以ド、参考例5
と同fiに処理し、淡緑色液体5.05gを得る。Engineering R spectrum y (filmJ elm-1:1
640 (-coygu) Reference Example 15 1-(2-(Piperidi7carbonylJethyl)piperazineTo a suspension of 3.73 g of piperazine in benzene, 4.38 g of triethylamine and N-(6-chlorobrobionyl) A solution of 5.50 g of pyrrolidine in 10-benzene was added to 2111 ml and heated under reflux for 19 hours. Hereinafter, Reference Example 5
5.05 g of pale green liquid was obtained.
工Rスペクトル ν (filmJ備−1:3300
(CNtu+ 1630 (−colJ:ン実施例15
1−<5. 4. 5−)リメトキシシンナモイルJ−
4−(2−(ビロリジ7カルボニルノ エチル〕ピペラ
ジン
参考例15で得た1−(2−(ビロリジ7カルボニルノ
エチル〕ピペラジン2.90gのクロロホルム601溶
液に、水冷攪拌下、5,4゜5−トリメトキシ桂皮酸ク
ロリド4.23gのクロロホルム40s/溶液をill
え、室温にて50分間攪拌する。以下、実施例14と同
様に処理し、黄色液体4.91gを得る。Engineering R spectrum ν (film J Bei-1:3300
(CNtu+ 1630 (-colJ:N Example 15 1-<5. 4. 5-) Rimethoxycinnamoyl J-
4-(2-(virolidi7carbonylnoethyl)piperazineTo a solution of 2.90 g of 1-(2-(virolidi7carbonylnoethyl)piperazine obtained in Reference Example 15 in chloroform 601, 5.4°5 - Ill a solution of 4.23 g of trimethoxycinnamic acid chloride in chloroform 40s/
Then, stir at room temperature for 50 minutes. Thereafter, the same procedure as in Example 14 was carried out to obtain 4.91 g of a yellow liquid.
工Rスペクトル ν (film )譚−1:1640
(−ooy<)
参考例16
1−〔2−(ピペリジ7カルボニルJエチル〕ピペラジ
ン
ピペラジン2.59gのベンゼン40sZ懸濁液に、ト
リエチルアミン3.05 gおよびN−(/−クロロプ
ロピオニル〕ピペリジン2.64gのベンゼン10耐溶
液を加え、15時間加熱還流する。以下、参考例3と同
様に処理し、淡橙色結晶1.5’9gを得る。Engineering R Spectrum ν (film)tan-1:1640
(-ooy<) Reference Example 16 1-[2-(Piperidi7carbonylJethyl]piperazineTo a suspension of 2.59 g of piperazine in benzene 40sZ, 3.05 g of triethylamine and 2. Add 64 g of a benzene 10-resistant solution and heat under reflux for 15 hours.Processing is carried out in the same manner as in Reference Example 3 to obtain 1.5'9 g of pale orange crystals.
工Rスペクトル ν (KBr 7個−1,−3300
(ンNHハ1635 (−ooy<)実施例16
1− (5,4,5−)リメトキシシンナモイル)−4
−(2−(ビペリジノカルポニルノエチル〕ピペ゛ラジ
ン
参考例16で得た1−(2−(ピペリジノカルボニル」
エチル〕ピペラジン1.58 gのクロロホルム3〇−
溶液に、室温攪拌下、5.4゜5−トリメトキシ桂皮酸
クロリF1.89gを加え、室温にて1時間攪拌する。Engineering R spectrum ν (KBr 7 pieces -1, -3300
(NNHHa1635 (-ooy<)Example 16 1-(5,4,5-)rimethoxycinnamoyl)-4
-(2-(biperidinocarbonylnoethyl)piperazine 1-(2-(piperidinocarbonyl) obtained in Reference Example 16)
ethyl]piperazine 1.58 g chloroform 30-
To the solution was added 1.89 g of 5.4° 5-trimethoxycinnamic acid chloride F while stirring at room temperature, and the mixture was stirred at room temperature for 1 hour.
以F1実施例14と同様に処理し、黄色液体2.60g
を得る。Thereafter, the process was carried out in the same manner as in F1 Example 14, and 2.60 g of yellow liquid was obtained.
get.
工Rスペクトル y (fi1mlc!11−1:1
640(−0ONζ〕
論考例1〜16で得られた化合物の核磁気共鳴スペクト
ルデーターな第1表に、又実施例1〜16で傅られた化
合物の核磁気共鳴スペクトルデーターな第2表にボす。Engineering R spectrum y (fi1mlc!11-1:1
640 (-0ONζ) A box is placed in Table 1 containing the nuclear magnetic resonance spectrum data of the compounds obtained in Discussion Examples 1 to 16, and in Table 2 containing the nuclear magnetic resonance spectrum data of the compounds obtained in Examples 1 to 16. vinegar.
参考例17
1−(2−(メチルアミノカルホ゛ニルノエチル〕ホモ
ピペラジン
ホモピペラジン5.90gのエタノール40s/浴液に
、炭酸カリウム4.10gおよびN−メチル−6−クロ
ロプロピオナミド3.60gのエタノール20m1溶液
を加え、20時間加熱還流する。以下、参考例1と同様
に処理し、緑色液体2、65 gを得る。Reference Example 17 1-(2-(Methylaminocarbonylnoethyl)homopiperazine To 5.90 g of homopiperazine in ethanol 40 s/bath solution, 4.10 g of potassium carbonate and 3.60 g of N-methyl-6-chloropropionamide were added. Add 20 ml of ethanol solution and heat under reflux for 20 hours.Then the mixture is treated in the same manner as in Reference Example 1 to obtain 2.65 g of green liquid.
工Rスペクトル ν (filnJ傭二1=3300
(>NI(+、 1640 (−0ON’、J実施例1
7
1− (3,4,5−1リメトキシシンナモイル)−4
−(2−(メチルアミ/カルボニルノエチル〕ホモピペ
ラジン
参考例17で得た1−C2−(メチルアミノカルボニル
)工fル〕ホモピペラジン2.0Dgのクロロホルム3
0g/溶液に、室温攪拌下、5゜4.5−)リメトキシ
桂皮酸クロリド3.20gを加え、室温にて15分間攪
拌する。以下、実施例1と同様に処理し、淡黄色結晶4
.03 gを得る。酢酸エチルエステルから再結晶し−
C1融点116〜121°の淡黄色鱗片状晶を得る。Engineering R spectrum ν (filnJ 1=3300
(>NI(+, 1640 (-0ON', J Example 1
7 1- (3,4,5-1 rimethoxycinnamoyl)-4
-(2-(Methylamino/carbonylnoethyl)homopiperazine1-C2-(methylaminocarbonyl)produced in Reference Example 17)2.0Dg of homopiperazine in chloroform 3
Add 3.20 g of 5°4.5-)rimethoxycinnamic acid chloride to 0 g/solution under stirring at room temperature, and stir at room temperature for 15 minutes. Thereafter, the same treatment as in Example 1 was carried out, and pale yellow crystals 4
.. Obtain 03 g. Recrystallized from ethyl acetate
Pale yellow scaly crystals with a C1 melting point of 116-121° are obtained.
工Rスペクトル y (KBrJcm ’:5590
(”NHJ、 1640 (−0ON、J元素分析値
021H31餐305
理論値 0 、62.20 i 817.71 i N
、 10.36実験値 0 、62.16 i Hl
7.73i N、 10.54参考例18
1−(2−(エチルアミノカルlニルJエチル〕ホモピ
ペラジン
ホモピペラジン5.50gのベンゼン80s?M濁液に
、トリエチルアミン5.55gおよびN−エチル−6−
クロロプロピオナミド5.72 gのベンゼン20sZ
溶液を加え、18時間・加熱還流する。以下、参考例6
と同様に処理し、淡黄色液体3.05gを得る。Engineering R spectrum y (KBrJcm': 5590
(NHJ, 1640 (-0ON, J elemental analysis value 021H31 305 theoretical value 0, 62.20 i 817.71 i N
, 10.36 experimental value 0 , 62.16 i Hl
7.73i N, 10.54 Reference Example 18 1-(2-(ethylaminocarnylJethyl)homopiperazineTo a suspension of 5.50 g of homopiperazine in benzene 80s?M, 5.55 g of triethylamine and N-ethyl- 6-
Chloropropionamide 5.72 g benzene 20sZ
Add the solution and heat to reflux for 18 hours. Below, reference example 6
Treat in the same manner as above to obtain 3.05 g of a pale yellow liquid.
工Rスペクトル y (fi1mJcs+ ’:33
00 DNH)、1635 (−aokJ<)実施例1
8
1− (3,4,5−1リメトキシシンナモイル) −
4−C2−(:r−チルアミ7カルボニルJエチル〕ホ
モピペラジン
参考例18で得た1−(2−(エチルアミノカルボニル
フエチル〕ホモピペラジン2.92gのクロロホルム3
0wt溶液に、室温攪拌F13゜4.5−)リメトキシ
桂皮酸りロリド4.32gケ加え、室温にて50分間攪
拌する。以下、実施例1と同様に処理し、黄褐色液体5
.96gを得る。Engineering R spectrum y (fi1mJcs+ ': 33
00 DNH), 1635 (-aokJ<) Example 1
8 1- (3,4,5-1 rimethoxycinnamoyl) -
4-C2-(:r-thylamino7carbonylJethyl)homopiperazine 2.92 g of 1-(2-(ethylaminocarbonyl phethyl)homopiperazine obtained in Reference Example 18) in chloroform 3
Add 4.32 g of rimethoxycinnamic acid chloride (stirred at room temperature F13°4.5-) to the 0 wt solution and stir at room temperature for 50 minutes. Hereinafter, the same treatment as in Example 1 was carried out, and the yellowish brown liquid 5
.. Obtain 96g.
工Rスペクトル y (film ) C1m−1:
3300 (、’NH)、 1645 (−0ON<J
参考例19
1−(2−<−10ビルアミ7カルボニ!リ エチル〕
ホモピペラジン
ホモピペラジン8.60gのベンゼン50m1%1濁液
に、トリエチルアミン8.64gおよヒ1−プロピル−
5−クロロプロピオナミド6.40gのベンゼン40−
溶液を加え、20時間加熱還流する。以下、参考例3と
同様に処理し、淡黄色液体6.50g?t−得る。Engineering R spectrum y (film) C1m-1:
3300 (,'NH), 1645 (-0ON<J
Reference Example 19 1-(2-<-10 bilamin 7 carboni! ethyl)
Homopiperazine To a suspension of 8.60 g of homopiperazine in 50 ml of benzene (1%), 8.64 g of triethylamine and 1-propyl-
5-chloropropionamide 6.40 g benzene 40-
Add the solution and heat to reflux for 20 hours. Thereafter, the same treatment as in Reference Example 3 was carried out, and 6.50 g of pale yellow liquid was used. t-get.
工Rスペクトル ν (fllm ) ex l:31
0 (ンNH)、1640 (−0ON<J実施例1
9
1− (3,4,5−)リメトキシシンナモイルJ−4
−(2−(プロピルアミノヵルメニルJエチル〕ホモピ
ペラジン
参考例19で得た1−(2−(プロピルアミ/カルボニ
ルJエチル〕ホモピペラジン6.00gのクロロホルム
50s+J#液に、室温攪拌下、3.4.5−トリメト
キシ桂皮曖クロリド8.66gt’1lllえ、室温に
て20分間攪拌する。以下、実施例1と同様に処理し、
褐色液体11.47gを得る。Engineering R spectrum ν (fllm) ex l:31
0 (NH), 1640 (-0ON<J Example 1
9 1-(3,4,5-)rimethoxycinnamoyl J-4
-(2-(Propylaminocarmenyl J-ethyl) homopiperazine 1-(2-(propylaminocarmenyl J-ethyl) homopiperazine obtained in Reference Example 19) 6.00 g of chloroform 50s + J# solution was added with stirring at room temperature. .4.5-Trimethoxycinnamonium chloride (8.66gt'lll) was added and stirred at room temperature for 20 minutes.Hereinafter, the same treatment as in Example 1 was carried out.
11.47 g of brown liquid are obtained.
工Rスペクトル ν (fllm)1−1:3300
DuH)、 1 645 (−aouこ)参考1
)120
l−(2−(イソプロピルアミノカルCニルJエチル〕
ホモピペラジン
ホモピペラジン68.20gのベンゼン200ナミド5
1.00gのベンゼン200耐溶液を加え、24時間加
熱還流する。反応後不溶物をF夫し、溶媒を溶失する。Engineering R spectrum ν (fllm)1-1:3300
DuH), 1 645 (-aouko) Reference 1
)120 l-(2-(isopropylaminocal C-nyl J ethyl)
Homopiperazine Homopiperazine 68.20g Benzene 200 Namide 5
Add 1.00 g of benzene 200 resistant solution and heat under reflux for 24 hours. After the reaction, insoluble materials are removed and the solvent is dissolved away.
残渣を酢酸エチルエステルに#FJl、塩酸水溶液にて
抽出する。水層は炭酸カリウムにてアルカリ性となし、
クロロホルム抽出する。先の不溶物は、炭酸カリウム水
ftI液およびクロロホルムの混液中へrJIJ工て振
とう。クロロホルム層(を分散し、先のクロロホルム抽
出液と合し、飽相食塩水にて洗浄、脱札溶媒を留去し、
優られた残d’に蒸留して、沸点175〜177° (
5mra Hg )の無色液体47゜00gを得る。The residue was extracted with ethyl acetate #FJl and an aqueous hydrochloric acid solution. The aqueous layer was made alkaline with potassium carbonate,
Extract with chloroform. The above insoluble matter was shaken by rJIJ into a mixed solution of potassium carbonate aqueous ftI solution and chloroform. Disperse the chloroform layer (disperse it, combine it with the previous chloroform extract, wash with saturated saline, and distill off the dewaxing solvent.
Distilled to a superior residue d' with a boiling point of 175-177° (
47.00 g of a colorless liquid of 5 mra Hg) are obtained.
工Rスペクトル y (f11mJcs+ ”:56
00 (ンNHハ1655 (−ooNぐ]実施例
20
1− <5.4.5−)リメトキシシンナモイルJ −
4−(2−(イソプロビルアミノ力ルボニルフエチル〕
ホモピペラジン
参考例20で得た1−(2−(イソプロピルアミノカル
ボニルJエチ砂〕ホモピペラジン1600gのクロロホ
ルム200d溶液に、室温攪拌下、3.4.5−)リメ
トキシ桂皮酸クロリド23.10gを加え、室温にて1
5分間攪拌する。以下、実施例1と同様に処理し、褐色
液体26.30 gを得る。Engineering R spectrum y (f11mJcs+ ”:56
00 (NHNHha1655 (-ooNgu) Example 20 1- <5.4.5-) Rimethoxycinnamoyl J -
4-(2-(isopropylaminocarbonylphethyl)
Homopiperazine To a solution of 1,600 g of 1-(2-(isopropylaminocarbonyl J ethysand) homopiperazine obtained in Reference Example 20 in 200 d of chloroform, 23.10 g of 3.4.5-)rimethoxycinnamic acid chloride was added under stirring at room temperature. , 1 at room temperature
Stir for 5 minutes. Thereafter, the same procedure as in Example 1 was carried out to obtain 26.30 g of a brown liquid.
工Rスペクトル v (fila+Jcs+−1:3
300 (>NH)、1640 (−ooh’、を
参考例21
1−(2−(プチルアミノヵルホ゛ニル−エチル〕ホモ
ピペラジン
ホモピペラジン8.68gのベンゼン50s/懸濁液に
、トリエチルアミン8.77gおよびN−ブチル−6−
クロロプロピオナミド乙10gのベンゼン501溶液を
加え、26時間加熱還流する。以下、参考例7と同様に
処堆し、黄色液体6.49 gを得る。Engineering R spectrum v (fila+Jcs+-1:3
300 (>NH), 1640 (-ooh', Reference Example 21 1-(2-(Butylaminocarbonyl-ethyl)homopiperazineTo a suspension of 8.68 g of homopiperazine in 50s/suspension of benzene, 8.77 g of triethylamine and N-butyl-6-
A solution of 10 g of chloropropionamide in benzene 501 was added, and the mixture was heated under reflux for 26 hours. Thereafter, it was treated in the same manner as in Reference Example 7 to obtain 6.49 g of a yellow liquid.
工Rスペクトル y (filmJm l:3280
(ンNH〕+ 1640 (−aoNc)実施例
21
1− (3,4,5−1リメトキシシンナモイル)−4
−C2−(ブチルアミノカルボニル少エチル〕ホモピペ
ラジン
参考例21で得た1−(2−(ブチルアミノカルボ二ノ
リエチル〕ホモピペラジン6.00gのクロロホルム6
0ゴ溶液に、室温攪拌下、3゜4.5−トリメトキシ桂
皮酸クロリド8.12gを加え、室温にて15分間攪拌
する。以下、実施例1と同様に処理し、褐色液体10.
80gを優る。Engineering R spectrum y (filmJm l:3280
(NH) + 1640 (-aoNc) Example 21 1- (3,4,5-1 rimethoxycinnamoyl)-4
-C2-(butylaminocarbonylpolyethyl)homopiperazine 6.00 g of 1-(2-(butylaminocarbonylethyl)homopiperazine obtained in Reference Example 21) in chloroform 6
8.12 g of 3°4.5-trimethoxycinnamic acid chloride was added to the Ogo solution while stirring at room temperature, and the mixture was stirred at room temperature for 15 minutes. Thereafter, the process was carried out in the same manner as in Example 1, and the brown liquid 10.
Better than 80g.
工Rス−<クトk y (filmJcsm l:
3300 (ン1JH)、1640 (−aoy<1
参考例22
1−(2−(イソブチルアミ7カルボニル)エチル〕ホ
モビペラジン
ホモビベラジン19.60gのベンゼン100m/ 懸
fli flに、トリエチルアミン19.70gおよび
N−イソブチル−5−クロロプロピオナミド16、OO
gのベンゼン100s/溶液を加え、21時間加熱還流
する。以下、参考例6と同一に処理し、黄色液体11.
54gを得る。Engineering Rsu-<kutok y (filmJcsm l:
3300 (N1JH), 1640 (-aoy<1
Reference Example 22 1-(2-(isobutylami7carbonyl)ethyl)homobiperazine To 19.60 g of homobiperazine suspended in 100 m/fli fl of benzene, 19.70 g of triethylamine and 16 N-isobutyl-5-chloropropionamide were added. ,OO
g of benzene 100s/solution is added and heated under reflux for 21 hours. Hereinafter, the same treatment as in Reference Example 6 was carried out, and yellow liquid 11.
Obtain 54g.
工Rスペクトh w (film ) cs+−1
+3280 <>NHJ、1640 (−ooNく)
実施例22
1− (3,4,5−トリメトキシシンナモイルJ−4
−C2−(イソブチルアミノカルボニル」エチルジホモ
ピペラジン
参考例22で得た1−(2−(インブチルアミノ力ルボ
ニルフエチル〕ホモピペラジン8.00gのクロロホル
ム150s/溶液に、室温攪拌ド、5.4.5−)リメ
トキシ桂皮醗クロリド10.85gを加え、室mにて2
0分間攪拌する。Engineering R spectrum h w (film) cs+-1
+3280 <>NHJ, 1640 (-ooNku)
Example 22 1-(3,4,5-trimethoxycinnamoyl J-4
-C2-(isobutylaminocarbonyl)ethyldihomopiperazine To a solution of 8.00 g of 1-(2-(isobutylaminocarbonyl)homopiperazine) obtained in Reference Example 22 in 150 s/chloroform was stirred at room temperature for 5.4 hours. .5-) Add 10.85 g of rimethoxycinnamon chloride and incubate in room M for 2 hours.
Stir for 0 minutes.
溶媒を留去し、残渣にベンゼンおよび塩酸水溶液を加え
−CfMとう。水層は炭酸カリウムにてアルカリ性ζな
し、クロロホルム抽出する。クロロホルム層は水洗、脱
水。溶媒を留去し、得られた残渣(15,40gJをカ
ラムクロマトグラフィー (シリカゲル、メタノール−
クロロホルム)により処理し、黄色液体11.10gを
得る。The solvent was distilled off, and benzene and an aqueous hydrochloric acid solution were added to the residue to form a -CfM solution. The aqueous layer is extracted with potassium carbonate without alkaline ζ and chloroform. The chloroform layer was washed with water and dehydrated. The solvent was distilled off, and the resulting residue (15.40 gJ) was subjected to column chromatography (silica gel, methanol-
chloroform) to obtain 11.10 g of a yellow liquid.
工Rスペクトル y (film ) ell−1=
5520 (ンNHJ、1640 <−aoy4)参考
例26
1−(2−(sθQ−フチルアミツ力ルボニルフエチル
〕ホモビベラジン
ホモビベラジン9.57gのベンゼン60s/懸濁液に
、トリエチルアミン947gおよびN−(aeo−ブチ
ル)−5−クロロプロピオナミド7、00 gのベンゼ
ン60s/溶液を加え、23時[#IJ加熱還流する。Engineering R spectrum y (film) ell-1=
5520 (NNHJ, 1640 <-aoy4) Reference Example 26 1-(2-(sθQ-phthylamytricarbonyl ethyl) homobiverazine To a suspension of 9.57 g of homoviverazine in benzene 60s/suspension, 947 g of triethylamine and N- (aeo-butyl)-5-chloropropionamide 7.00 g of benzene 60s/solution was added and heated to reflux at 23:00 [#IJ].
以下、参考例7と同様に処理し、黄色液体7.58gを
得る。Thereafter, the same procedure as in Reference Example 7 was carried out to obtain 7.58 g of a yellow liquid.
IRスペクトル y (film ) am l:3
10 (ンME)J 1640 (−0ONく)実
施例23
1− C5,4,5−)リメトキシシンナモイル)
4 (2(neo−プチルアミノ力ルボニルノエチル
〕ホモピペラジン
参考例25で得た1−(2−(−・0−ブチルアミ7カ
ルボニ/I/)エチル〕ホモピペラジン乙00gのクロ
ロホルム60W1を溶液に、室温攪拌下、3,4.5−
トリメトキシ桂皮酸クロリド9.48g4I:[え、室
温にて20分間攪拌する。IR spectrum y (film) am l:3
10 (ME) J 1640 (-0ON) Example 23 1-C5,4,5-)rimethoxycinnamoyl)
4 (2(neo-butylaminoethyl)homopiperazine1-(2-(-・0-butylamino7carbony/I/)ethyl)homopiperazine obtained in Reference Example 25 Add 00 g of chloroform 60W1 to a solution, 3,4.5- under stirring at room temperature
Trimethoxycinnamic acid chloride 9.48g 4I: Stir at room temperature for 20 minutes.
以下、実施例1と同様に処理し、褐色液体11゜86g
t−得る。Thereafter, the process was carried out in the same manner as in Example 1, and 11°86 g of brown liquid was obtained.
t-get.
工RXベクトルy (filmJcm−1:3300
(ンMH)、 1640 (−ooNぐ)参考的2
4
1−(2(tert−ブチルアミ7カルボニルJエチル
〕ホモピペラジン
ホモピペラジン24.50gのベンゼン1001懸〜吟
に、トリエチルアミン24.80gおよびN −(te
rt−ブチル)−6−クロロプロピオナミド20.00
gのベンゼン100s/溶液を加え、165時間加熱還
流する。以下、参考例5と同様に処理し、黄色液体14
.79gを得る。Engineering RX vector y (filmJcm-1:3300
(nMH), 1640 (-ooNgu) Reference 2
4 1-(2(tert-butylamino7carbonylJethyl)homopiperazine To 24.50 g of homopiperazine and 1001 g of benzene, 24.80 g of triethylamine and N-(te
rt-butyl)-6-chloropropionamide 20.00
Add 100 g of benzene/solution and heat to reflux for 165 hours. Hereinafter, the yellow liquid 14 was treated in the same manner as in Reference Example 5.
.. Obtain 79g.
工Rスペクトル ν (fi’1m )国−1=330
0 DNaハ1645 (−oohく)実施例24
1− (3,4,5−)リメトキシシンナモイル)
4 (2(tart−ブチルアミ7カルボニルJエチ
ル〕ホモピペラジン
参考例24で得た1 (2−(tert、−ブチルア
ミ7カルボニルノエチル〕ホモピペラジン1000gの
クロロホルム150g/溶液に、室温情拌F、3.4.
5−1リメトキシ桂皮酸クロリド13.50gを加え、
室温にて15分間攪拌する。以F1実施例1と同様に処
理し、褐色液?+18.31gを得る。Engineering R spectrum ν (fi'1m) country - 1 = 330
0 DNaha1645 (-oohku)Example 24 1-(3,4,5-)rimethoxycinnamoyl)
4 (2(tart-butylami7carbonylJethyl)homopiperazine) To a solution of 1000g of 1(2-(tert,-butylamino7carbonylnoethyl)homopiperazine) in chloroform, stirred at room temperature F, 3 .4.
Add 13.50 g of 5-1 rimethoxycinnamic acid chloride,
Stir for 15 minutes at room temperature. Thereafter, the process was carried out in the same manner as in F1 Example 1, and a brown liquid was obtained. +18.31g is obtained.
工Rスペクトル y (filmJcml:3320
(ンNHJ 、 1645 (−0oNり)参考
例25
1−C2−(ペンチルアミノ力ルボニルフエチル〕ホモ
ピペラジン
ホモピペラジン6.76gのベンゼン50si!II濁
液に、トリエチルアミン6、83 gおよびN −ペン
チル−3−クロロブロビオナミ)”6.0[1gのベン
ゼン50g/溶液を加え、23時間加熱還流する。以下
、参考例7と同様に処理し、黄色液体4.55gを得る
。Engineering R spectrum y (filmJcml:3320
(NHJ, 1645 (-0oN)) Reference Example 25 1-C2-(pentylaminocarbonyl ethyl) homopiperazine To a suspension of 6.76 g of homopiperazine in benzene 50si!II, 6.83 g of triethylamine and N-pentyl Add 50 g/solution of 1 g of benzene and heat to reflux for 23 hours. The following procedure is carried out in the same manner as in Reference Example 7 to obtain 4.55 g of a yellow liquid.
工Rスペクトル ν (film J備−1:5soo
(、mH]、1640 (−ooh、)実施例2
5
1− (3,4,5−)リメトキシシンナモイル) −
4−(2−(:ンチルアミ/カルボニルフエチル〕ホモ
ピペラジン
al1例25で得た1−(2,−(ベンチルアミノカル
ポニルノエチル〕ホモピペラジン4.20gのクロロホ
ルム50111!浴液に、室温攪拌ド、3.4.5−1
リメトキシ桂皮醗クロリド5.67gをIJLIえ、室
温にて20分間攪拌する。以下、実施例22と同様に処
理し、淡黄色液体7.50gを得る。Engineering R spectrum ν (film J-1:5soo
(, mH], 1640 (-ooh,) Example 2
5 1- (3,4,5-)rimethoxycinnamoyl) -
4.20 g of 1-(2,-(bentylaminocarbonylnoethyl)homopiperazine obtained in Example 25) was added to the chloroform 50111! bath solution with stirring at room temperature. 3.4.5-1
Add 5.67 g of rimethoxycinnamate chloride to the IJLI and stir at room temperature for 20 minutes. Thereafter, the same procedure as in Example 22 was carried out to obtain 7.50 g of a pale yellow liquid.
工Rスペクトル y (film ) 鋸1:331
0(ンNHハ1645 (−cou()参考例26
1−(2−(ヘキシルアミノ力ルボニルノエチル〕ホモ
ピペラジン
ホモピペラジン6、78 gに、トリエチルアミン6.
85gおよびn−へキシル−5−クロロプロピオナミド
6.50gのベンゼン100g1溶液を加え、22.5
時間加熱還流する。以下、参考例7と同様に処理し2、
黄褐色液体6.60gを得る。Engineering R spectrum y (film) Saw 1:331
0(nNHha1645 (-cou()) Reference Example 26 1-(2-(hexylaminocarbonylnoethyl)homopiperazineTo 6.78 g of homopiperazine, 6.0 g of triethylamine was added.
A solution of 85 g and 6.50 g of n-hexyl-5-chloropropionamide in 100 g of benzene was added, and 22.5
Heat to reflux for an hour. Hereafter, the process was carried out in the same manner as in Reference Example 7.
6.60 g of a tan liquid are obtained.
工Rスペクトル ν(film ) L:ml:530
0 (ンNHJ + 1 640 (−aoN
c〕実施例26
1− (3,4,5−)リメトキシシン+モイル) −
4−C2−(ヘキシルアミ7カルボニルンエチル〕ホモ
ピペラジン
参考例26で得た1−(2−(ヘキシルアミ7カルボニ
ルJエチル〕ホモピペラジン6.00gのクロロホルム
50m/溶液に、室温攪拌下、3.4.5−トリメトキ
シ桂皮版りロリド乙60gを加え、室温にて10分間攪
拌する。溶媒を留去し、残渣にベンゼンおよび水を加え
て振とう。水層および不溶液体を分取し、水酸化ナトリ
ウム水溶液にてアルカリ性となし、クロロホルム抽出す
る。クロロホルム層は水洗、脱水。Engineering R spectrum ν(film) L:ml:530
0 (NHJ + 1 640 (-aoN
c] Example 26 1- (3,4,5-)rimethoxycin + moyl) -
4-C2-(hexylami7carbonyl-ethyl)homopiperazine To a solution of 6.00 g of 1-(2-(hexylami7carbonylJ-ethyl)homopiperazine) obtained in Reference Example 26 in 50ml of chloroform was added 3.4 ml of chloroform with stirring at room temperature. Add 60 g of 5-trimethoxycinnamon loride Otsu and stir at room temperature for 10 minutes. Distill the solvent, add benzene and water to the residue, and shake. Separate the aqueous layer and insoluble material, and add hydroxylated Make alkaline with an aqueous sodium solution and extract with chloroform.The chloroform layer is washed with water and dehydrated.
溶媒を留去し、褐色液体10.61gを得る。The solvent was distilled off to obtain 10.61 g of a brown liquid.
工Rスペクトk y (filmJm l:331
0(ンNH)+ 1645 (−ooN4)奈考例27
1−(2−(シクロへ午シルアミノ力ルボニルノエチル
〕ホモピペラジン
ホモピペラジン5.28gのベン上250g/懸濁液に
、トリエチルアミン5.33gおよびN −ンクロへキ
シル−6−クロロプロピオナミド5゜00gのベンゼン
40耐溶液を]J[]え、226.5時間1111熱還
する。以下、参考例5と同様に処理し、無色液体4.2
5gを得る。Engineering R spectrum k y (filmJm l:331
0(NH)+ 1645 (-ooN4)Na Example 27 1-(2-(cyclohexylamino-carbonylnoethyl)homopiperazineTo a suspension of 5.28 g of homopiperazine at 250 g/suspension, 5.0 g of triethylamine was added. A benzene 40-resistant solution of 33 g and 500 g of N-chlorohexyl-6-chloropropionamide was heated to reflux for 226.5 hours at 1111°C. liquid 4.2
Obtain 5g.
IRスペクトル y、 (filmJ ”−1:530
0 (ンNH)、1640 (−aoNく)実施例27
エチル〕ホモピペラジン
参考−]27で得た1−C2−(シクロへキシルアミ/
カルボニルノエナル〕ホモピペラジン400gのクロロ
ホルム50s/溶液に、室温攪ffF、5.4.5−)
リメトキシ桂皮酸クロリド4.86gを加え、室温にて
10分間攪拌する。IR spectrum y, (filmJ”-1:530
0 (NH), 1640 (-aoN) Example 27 Ethyl] homopiperazine reference -] 1-C2-(cyclohexylamine/
Carbonylnoenal] Homopiperazine 400g in chloroform 50s/solution, stirred at room temperatureffF, 5.4.5-)
Add 4.86 g of rimethoxycinnamic acid chloride and stir at room temperature for 10 minutes.
以ド、実施例1と同様に処理し、黄−免液体6゜95g
を得る。Thereafter, the treatment was carried out in the same manner as in Example 1, and 6.95 g of yellow-free liquid was obtained.
get.
工Rスペクトル ν(filmJcsml:3300
C>yH)、1 640 (−aoN;)参考例2
8
1−(2−(ジメチルアミ/カルボニルJエチル〕ホモ
ピペラジン
ホモピペラジン5.17gに、トリエチルアミン5.2
2 gおよびN、N−ジメチル−6−クロロプロピオナ
ミド3.50gのベンゼン90s/溶液を加え、26時
間加熱還流する。以下、参考例1と同様に処理し、黄褐
色液体1.50g&得る。Engineering R spectrum ν(filmJcsml:3300
C>yH), 1 640 (-aoN;) Reference Example 2
8 1-(2-(dimethylamino/carbonyl J ethyl) homopiperazine To 5.17 g of homopiperazine, 5.2 g of triethylamine
2 g and 3.50 g of N,N-dimethyl-6-chloropropionamide in 90 s/solution of benzene are added and heated under reflux for 26 hours. Thereafter, the same procedure as in Reference Example 1 was carried out to obtain 1.50 g of a yellow-brown liquid.
工Rスペクトル ν (film )国−1:5500
(ンNl(ハ1630 (−ooyc)実施例28
1−(3,4,5−1リメトキシシンナモイJu) −
4−C2−(ジメチルアミ/カルボニルJエチル〕ホモ
ピペラジン
謬考例28で得た1−C2−(ジメチルアミノ力ルボニ
ルノエチル〕ホモピペラジン1.40gのクロロホルム
20s/溶液に、室温攪拌下、3.4.5−)リメトキ
シ桂皮酸クロリド2.16gを加え、室温にて15分間
攪拌する。以下、実施例1と同様に処理し、淡黄色結晶
2.65gを得る。酢酸エチルエステルから再結晶して
、融点100〜102°の淡黄色板状晶を得る。Engineering R spectrum ν (film) country-1:5500
(Nl(Ha1630 (-ooyc)Example 28 1-(3,4,5-1rimethoxycinnamoyiJu)-
4-C2-(dimethylamino/carbonylJethyl)homopiperazineTo a solution of 1.40 g of 1-C2-(dimethylaminocarbonylnoethyl)homopiperazine obtained in Example 28 in chloroform for 20 s/while stirring at room temperature, 3. 4.5-) Add 2.16 g of rimethoxycinnamic acid chloride and stir at room temperature for 15 minutes.Proceed in the same manner as in Example 1 to obtain 2.65 g of pale yellow crystals.Recrystallize from ethyl acetate. As a result, pale yellow plate crystals with a melting point of 100-102° are obtained.
工Rスペクトル し (KBrJ備−1:1640(−
0ONζ」
元素分析値 0f12H33N305
理論値 0 、62.99i1(、7,93;ML 1
0.02実験値 0 、62.82;H,8,00;N
、 10.03参考例29
1−(2−<ジエチルアミノカルごニル)エチル〕ホモ
ピペラジン
ホモピペラジン7.30gに、トリエチルアミン7.4
0gおよびN、N−ジエチル−6−クロロプロピオナミ
ド6.00gのベンゼン100耐溶液を加え、22時間
加熱還流する。以下、参考例7と同様に処理し、無色液
体4.90gを優る。Engineering R spectrum (KBrJ Bi-1:1640(-
0ONζ” Elemental analysis value 0f12H33N305 Theoretical value 0,62.99i1(,7,93;ML 1
0.02 experimental value 0, 62.82; H, 8,00; N
, 10.03 Reference Example 29 1-(2-<diethylaminocargonyl)ethyl]homopiperazine To 7.30 g of homopiperazine, 7.4 g of triethylamine was added.
A benzene 100 resistant solution of 0 g and 6.00 g of N,N-diethyl-6-chloropropionamide was added, and the mixture was heated under reflux for 22 hours. Thereafter, the same treatment as in Reference Example 7 was carried out, and 4.90 g of the colorless liquid was obtained.
工Rスペクトル ν(filmJ C1m l。Engineering R spectrum ν(filmJ C1ml l.
3300 (ンNHハ1bsa (−ooNc)実施
例29
1− (3,4,5−)リメトキシシンナモイ”J
4 (2−(ジエチルアミ7カルボニルノエチル〕
ホモピペラジン ゛
参考例29で得た1−(2−(ジエチルアミ7カルボニ
ルノエチル〕ホモピペラジン4.60gのクロロホルム
5〇−溶液に、室温攪拌下、3.4.5−トリメトキシ
桂皮飯クロリド6.2og”a:noえ、室温にて20
分間攪拌する。以下、実施例1と同様に処理し、褐色液
体9.OOgを得る。3300 (NHHa1bsa (-ooNc)Example 29 1-(3,4,5-)rimethoxycinnamoy"J
4 (2-(diethylami7carbonylnoethyl)
Homopiperazine To a solution of 4.60 g of 1-(2-(diethylami7carbonylnoethyl)homopiperazine obtained in Reference Example 29 in chloroform) was added 3.4.5-trimethoxycinnamic chloride 6. 2og"a: no, 20 at room temperature
Stir for a minute. Thereafter, the process was carried out in the same manner as in Example 1, and the brown liquid 9. Get OOg.
工Rスペクトル ν (filmJcmぺ:1640
(−0ONで)
峯考例60
1−(2=−(ジプロピルアミ7カルボニルンエチル〕
ホモピペラジン
pプロピオナミド6、00 gのベンゼン100m/溶
液を加え、225時間加熱還流する。以下、参考例7と
同様に処理し、無色液体4.65gを優る。Engineering R spectrum ν (filmJcmpe:1640
(-0ON) Mine example 60 1-(2=-(dipropylamide 7 carbonylene ethyl)
A solution of 6.00 g of homopiperazine p-propionamide in 100 m/solution of benzene is added and heated under reflux for 225 hours. Thereafter, the same treatment as in Reference Example 7 was carried out, and 4.65 g of the colorless liquid was obtained.
IRスペクトル ’ (film ) 1z 1:3
410(ンNH)、1650 (0oNC)′、A地f
450
1− (3,4,5−トリメトキシシンナモイルJ−4
−(2−(ジ千午プロピルアミノカル っボニルノエチ
ル〕ホモピペラジン
参考例50で得た1−C2−(ジや≠プロピ 〕ルγミ
ノカルボニルJエチル〕ホモピペラジン4.50gのク
ロロホルム50sZ浴液に、室温攪拌ド、5.4.5−
トリメトキシ桂皮酸クロリド5.40gを加え、室温に
て10分間攪拌する。IR spectrum' (film) 1z 1:3
410 (NH), 1650 (0oNC)', A ground f
450 1-(3,4,5-trimethoxycinnamoyl J-4
-(2-(disengopropylaminocarbonylnoethyl)homopiperazine1-C2-(diy≠propylaminocarbonylJethyl)homopiperazine obtained in Reference Example 50 4.50g of chloroform 50sZ bath solution , room temperature stirring, 5.4.5-
Add 5.40 g of trimethoxycinnamic acid chloride and stir at room temperature for 10 minutes.
以下、実施例1と同様に処理し、褐色液体8,50gを
得る。Thereafter, the same procedure as in Example 1 was carried out to obtain 8.50 g of a brown liquid.
工Rスペクトル ν(film ) 譚1゜1640
<−ooN@フ
参考例31
1−(2−<ヒロリジ7カルざニルノエチル〕ホモピペ
ラジン
ホモピペラジン4.99gのベンゼン50sJM濁液に
、トリエチルアミン5.04gおよびN −(3−クロ
ルプロピオニル少ピロリジン4.05gのベンゼン20
w1溶液を加え、18時間加熱還流する。以下、参考例
5と同様に処理し、淡黄色液体4.90gを得る。Engineering R spectrum ν (film) Tan 1゜1640
<-ooN@F Reference Example 31 1-(2-<Hirolidi7carzanylnoethyl]homopiperazineTo a suspension of 4.99 g of homopiperazine in 50sJM of benzene, 5.04 g of triethylamine and N-(3-chloropropionyl oligopyrrolidine) 4. 05g benzene20
Add w1 solution and heat to reflux for 18 hours. Thereafter, the same treatment as in Reference Example 5 was carried out to obtain 4.90 g of a pale yellow liquid.
XRスペクトル y (film ) csa−1:
55oo (> Ml(J、1625 <−aoN<を
実施例61
1− (3,4,5−1リメトキシシンナモイルJ−4
−(2−(ビロリジ7カルボニルフエチル〕ホモピペラ
ジン
疹考的61で得た1−(2−(ビロリジノヵルホ゛ニル
ノエチル〕ホモピペラジン4.72 gのクロロホルム
60m1溶液に、室温攪拌下、3゜4.5−)リメトキ
シ桂皮師クロリド6.46gのクロロホルム4.Osg
溶液を加え、室温にて50分間攪拌する。以下、実施例
14と同様に処理し、黄色液体682gを得る。XR spectrum y (film) csa-1:
55oo (>Ml(J, 1625 <-aoN<) Example 61 1-(3,4,5-1 rimethoxycinnamoyl J-4
-(2-(Virrolidinocarbonylnoethyl)homopiperazine Experimental 61) To a solution of 4.72 g of 1-(2-(virolidinocarbonylnoethyl)homopiperazine) in 60 ml of chloroform was stirred at room temperature. 3゜4.5-) Rimethoxycinnamate chloride 6.46g Chloroform 4.Osg
Add the solution and stir at room temperature for 50 minutes. Thereafter, the same treatment as in Example 14 was carried out to obtain 682 g of a yellow liquid.
工Rスペクトル ν (film J m l:164
0(−0ONぐ〕
参考例32
1−(2−(ピペリジノ力ルボニルノエチル〕ホモピペ
ラジン
ホモピペラジン6、08 gのベンゼン60m/懸#液
に、トリエチルアミン3.11gおよびN−(5−クロ
ロプロピオニルJ ピペリジン2.70gのベンゼン5
0m溶液を加え、15時間加熱還流する。以下、参考例
3と同様に処理し、無色液体2.07 gを得る。Engineering R spectrum ν (film J m l:164
0(-0ON) Reference Example 32 1-(2-(piperidinocarbonylnoethyl)homopiperazine6.08 g of benzene 60m/suspended in a solution containing 3.11 g of triethylamine and N-(5-chloropropionyl) J piperidine 2.70 g benzene 5
Add 0m solution and heat to reflux for 15 hours. Thereafter, the same treatment as in Reference Example 3 was carried out to obtain 2.07 g of a colorless liquid.
IRスペクトル W (film)cs+ 1:5s
5o <>yH)+ 16.so (−ooN<)実施
例32
1− (3,4,5−トリメトキシシンナモイk) −
4−C2−(ヒヘリジ7カルボニルフエチル〕ホモピペ
ラジン
参考例32で得た1−(2−(ピペリジ7カルメニルフ
エチル〕ホモピペラジン1.84gのクロロホルム40
s/溶液に、室温攪拌下、6゜4.5−)リメトキシ桂
皮酸クロリド2.57gを加え、室温にて1時間攪拌す
る。以下、実施例1と同様に処理し、黄色液体3.22
g′4r:4る。IR spectrum W (film)cs+ 1:5s
5o<>yH)+16. so (-ooN<) Example 32 1- (3,4,5-trimethoxycinnamoyk) -
1.84 g of 1-(2-(piperidi7carmenylphethyl)homopiperazine) obtained in Reference Example 32 in chloroform 40
2.57 g of 6°4.5-)rimethoxycinnamic acid chloride was added to the solution under stirring at room temperature, and the mixture was stirred at room temperature for 1 hour. Hereinafter, the process was carried out in the same manner as in Example 1, and the yellow liquid 3.22
g'4r: 4ru.
工Rスペクトル y (film ) m l:16
40 (−aoNく)
参考例17〜32で得られた化合物の核磁気共鳴スペク
トルデーターを第3衣に・又実施例17〜52で得られ
た化合物の核磁気共鳴スペクトルデーターを第4表にボ
す。Engineering R spectrum y (film) ml:16
40 (-aoN) The nuclear magnetic resonance spectrum data of the compounds obtained in Reference Examples 17 to 32 are shown in Table 3.The nuclear magnetic resonance spectrum data of the compounds obtained in Examples 17 to 52 are shown in Table 4. Boss.
Claims (1)
鎖状のアルキル基、又番コ伏素数5〜7のシクロアルキ
ル基であるアミン基を表わすが、もしくはR1およびR
2が同一もしくは異なって、炭素数1〜乙の直鎖状もし
くは分枝鎖状のアルキル基であるアミノ基を表わすか、
もしくはR1とR2とが一緒ケこなって環状となったア
ミ7基を表わし、nは2又は乙の整数を表わす。)で示
される1−(3,4,5−)リメトキシシンナモイル)
−4−アミノカルボニルエチル置換ピペラジン及びホモ
ピペラジン誘導体、及びその薬理学的に許容しう゛る酸
付加塩。 2、一般式 R2が炭素数1〜6の直鎖状もしくは分枝鎖状のアルキ
ル基、又は炭素数5〜7のシクロアルキル基であるアミ
ノ基を表わすか、もしくはR1およびB2が同一もしく
は異なって、炭素数1〜6の直鎖状もしくは分枝鎖状の
アルキル基であるアミノ基を表わすか、もしくはR1と
R2とが一緒になって環状となったアミ7基を表わし、
nは2又は6の整数を表わす。)で示される1 −C5
,4,5−)リメトキシシンナモイル)−4−アミノカ
ルボニルエチル置換ピペラジン及びホモピペラジン誘導
体、及びその薬理学的に許容しつる酸付加塩の製造方法
tこおいて、次の一般式 ) でボされる1−アミノカルボニルエチルlif&ピペラ
ジン又はホモピペラジ/@導体と、次の一般式 (式中、Xはハロゲン原子、殊にクール又はブーム原子
を表わす。) で示される3、4.5−)リメトキシ桂皮酸ハロゲニド
とを反応させることを特徴とする方法。 3一般式 りR2か炭素数1〜乙の直鎖状もしくは分枝鎖状ノア
ルキル基、又は炭素数5〜7のシクロアルキル基である
アミ7基を表わすか、もしくはR1およびR2が同一も
しくは異なって、炭素数1〜6の直鎖状もしくは分枝鎮
状のアルキル基であるアミノ基を表わすか、もしくはR
1とR2とが一緒になって環状となったアミ/基を表わ
し、nは2又は3のJl数を表わす。) で示される1−(3,4,5−)リメトキシンンナモイ
ル)−4−アミノカルlニルエチル置換ピペラジン及び
ホモピペラジン誘導体、及びその#理学的に許容しつる
酸付加塩の製造方法において、次の一般式 (式中、nは前述と同意義を表わす。)で示される1−
(3,4,5−トリメトキシンンナモイル)ヒペラジン
又はホモピペラジンと、次の一般式 Xはハロゲン原子、殊にクロル又にfブロム原子を衣わ
す。) で示されるアミ7カルボニルエチルハライド。 とを、脱酸剤としての塩基の存在rtこ反応させるJと
を特徴とする方法。[Scope of Claims] 1 The general formula R2 represents an amine group which is a l1lliliI-like or branched alkyl group having an ash number of 1 to 7, or a cycloalkyl group having an ash number of 5 to 7, or R1 and R
2 are the same or different and represent an amino group which is a linear or branched alkyl group having 1 to 2 carbon atoms;
Alternatively, R1 and R2 represent a cyclic group formed by combining R1 and R2, and n represents an integer of 2 or O. ) 1-(3,4,5-)rimethoxycinnamoyl)
-4-aminocarbonylethyl-substituted piperazine and homopiperazine derivatives, and pharmacologically acceptable acid addition salts thereof. 2. The general formula R2 represents a linear or branched alkyl group having 1 to 6 carbon atoms, or an amino group which is a cycloalkyl group having 5 to 7 carbon atoms, or R1 and B2 are the same or different. represents an amino group which is a linear or branched alkyl group having 1 to 6 carbon atoms, or represents an amine group in which R1 and R2 are combined to form a cyclic structure,
n represents an integer of 2 or 6. ) denoted by 1-C5
,4,5-)rimethoxycinnamoyl)-4-aminocarbonylethyl-substituted piperazine and homopiperazine derivatives, and a method for producing pharmacologically acceptable sucrose addition salts thereof, where the following general formula) 1-aminocarbonylethyl lif&piperazine or homopiperazi/@ conductor and 3,4.5-) represented by the following general formula (wherein, X represents a halogen atom, especially a cool or boom atom) A method characterized by reacting with rimethoxycinnamic acid halide. 3 General formula R2 or straight chain or branched chain Noah having 1 to 2 carbon atoms
R1 and R2 are the same or different and represent a linear or branched alkyl group having 1 to 6 carbon atoms; represents a certain amino group, or R
1 and R2 together represent a cyclic amino/group, and n represents a Jl number of 2 or 3. ) 1-(3,4,5-)rimethoxinannamoyl)-4-aminocarlnylethyl-substituted piperazine and homopiperazine derivatives, and their #physically acceptable phosphoric acid addition salts, in the method for producing the following: 1- represented by the general formula (wherein n represents the same meaning as above)
With (3,4,5-trimethoxynnnamoyl)hyperazine or homopiperazine, the following general formula X covers a halogen atom, especially a chlorine or f-brome atom. ) Ami7 carbonylethyl halide. and the presence of a base as a deoxidizing agent.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP57071471A JPS58189170A (en) | 1982-04-30 | 1982-04-30 | 1-(3,4,5-trimethoxycinnamoyl)-4-aminocarbonyl-ethyl- substituted piperazine and homopiperazine derivative and its preparation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP57071471A JPS58189170A (en) | 1982-04-30 | 1982-04-30 | 1-(3,4,5-trimethoxycinnamoyl)-4-aminocarbonyl-ethyl- substituted piperazine and homopiperazine derivative and its preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS58189170A true JPS58189170A (en) | 1983-11-04 |
Family
ID=13461552
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP57071471A Pending JPS58189170A (en) | 1982-04-30 | 1982-04-30 | 1-(3,4,5-trimethoxycinnamoyl)-4-aminocarbonyl-ethyl- substituted piperazine and homopiperazine derivative and its preparation |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS58189170A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4656172A (en) * | 1984-09-17 | 1987-04-07 | Terumo Kabushiki Kaisha | 1-[5-(3,4,5-Trimethoxy phenyl)-2,4-pentadienoyl]-4-(substituted carbonylmethyl)-piperazines having vasodilating activity |
-
1982
- 1982-04-30 JP JP57071471A patent/JPS58189170A/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4656172A (en) * | 1984-09-17 | 1987-04-07 | Terumo Kabushiki Kaisha | 1-[5-(3,4,5-Trimethoxy phenyl)-2,4-pentadienoyl]-4-(substituted carbonylmethyl)-piperazines having vasodilating activity |
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