JPH0357897B2 - - Google Patents
Info
- Publication number
- JPH0357897B2 JPH0357897B2 JP57122231A JP12223182A JPH0357897B2 JP H0357897 B2 JPH0357897 B2 JP H0357897B2 JP 57122231 A JP57122231 A JP 57122231A JP 12223182 A JP12223182 A JP 12223182A JP H0357897 B2 JPH0357897 B2 JP H0357897B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- phenyl
- benzodiazonine
- hexahydro
- dihydrochloride
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000004519 manufacturing process Methods 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000012458 free base Substances 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 16
- -1 p-fluorobenzoylpropyl group Chemical group 0.000 claims description 14
- 238000007796 conventional method Methods 0.000 claims description 13
- DGNXEVQSRKALRS-UHFFFAOYSA-N 1-phenyl-2h-2,6-benzodiazonine Chemical class C1=CC=CC=C1C1=C2C=CC=CC2=CN=CC=CN1 DGNXEVQSRKALRS-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims 5
- 239000002904 solvent Substances 0.000 claims 5
- 239000000047 product Substances 0.000 claims 4
- 239000003638 chemical reducing agent Substances 0.000 claims 3
- BNQMPUFBEBLZGA-UHFFFAOYSA-N 2-(4-fluorophenyl)-1,3-dioxolane Chemical compound C1=CC(F)=CC=C1C1OCCO1 BNQMPUFBEBLZGA-UHFFFAOYSA-N 0.000 claims 2
- 239000007795 chemical reaction product Substances 0.000 claims 2
- 238000003776 cleavage reaction Methods 0.000 claims 2
- 239000012022 methylating agents Substances 0.000 claims 2
- 230000007017 scission Effects 0.000 claims 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- 238000005259 measurement Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000007788 liquid Substances 0.000 description 15
- 238000004364 calculation method Methods 0.000 description 13
- 239000013078 crystal Substances 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 229910010082 LiAlH Inorganic materials 0.000 description 8
- 230000000202 analgesic effect Effects 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 238000000921 elemental analysis Methods 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- UVZGOOXAARJPHD-UHFFFAOYSA-N butan-2-one;methanol Chemical compound OC.CCC(C)=O UVZGOOXAARJPHD-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000003533 narcotic effect Effects 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010044565 Tremor Diseases 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- RGPDEAGGEXEMMM-UHFFFAOYSA-N Nefopam Chemical compound C12=CC=CC=C2CN(C)CCOC1C1=CC=CC=C1 RGPDEAGGEXEMMM-UHFFFAOYSA-N 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 229960000751 nefopam Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- GTIOLZZDMYEQGY-UHFFFAOYSA-N 2-(2,4,5-trimethoxyphenyl)acetic acid Chemical compound COC1=CC(OC)=C(OC)C=C1CC(O)=O GTIOLZZDMYEQGY-UHFFFAOYSA-N 0.000 description 1
- QBJIMTPENIGDOG-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)acetyl chloride Chemical compound COC1=CC=C(CC(Cl)=O)C=C1OC QBJIMTPENIGDOG-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 1
- FGTYTUFKXYPTML-UHFFFAOYSA-N 2-benzoylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 FGTYTUFKXYPTML-UHFFFAOYSA-N 0.000 description 1
- RMNFNJLSEHCPTJ-UHFFFAOYSA-N 4-(4-methoxyphenyl)butanoyl chloride Chemical compound COC1=CC=C(CCCC(Cl)=O)C=C1 RMNFNJLSEHCPTJ-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 206010013642 Drooling Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 208000008630 Sialorrhea Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 230000000985 convulsing effect Effects 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 238000011076 safety test Methods 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12223182A JPS5913767A (ja) | 1982-07-15 | 1982-07-15 | 新規の１−フエニル−２，６−ベンゾジアゾニン誘導体及びその製法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12223182A JPS5913767A (ja) | 1982-07-15 | 1982-07-15 | 新規の１−フエニル−２，６−ベンゾジアゾニン誘導体及びその製法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5913767A JPS5913767A (ja) | 1984-01-24 |
| JPH0357897B2 true JPH0357897B2 (no) | 1991-09-03 |
Family
ID=14830812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12223182A Granted JPS5913767A (ja) | 1982-07-15 | 1982-07-15 | 新規の１−フエニル−２，６−ベンゾジアゾニン誘導体及びその製法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5913767A (no) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61158872A (ja) * | 1984-12-28 | 1986-07-18 | ハリマセラミック株式会社 | キヤスタブル耐火物 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3549620A (en) * | 1966-06-30 | 1970-12-22 | Sandoz Ag | Substituted hexahydro-1-phenyl-1h-2,6-benzodiazonines |
-
1982
- 1982-07-15 JP JP12223182A patent/JPS5913767A/ja active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3549620A (en) * | 1966-06-30 | 1970-12-22 | Sandoz Ag | Substituted hexahydro-1-phenyl-1h-2,6-benzodiazonines |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5913767A (ja) | 1984-01-24 |
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