HU179836B - Process for producing phenyl-morphane derivatives - Google Patents
Process for producing phenyl-morphane derivatives Download PDFInfo
- Publication number
- HU179836B HU179836B HU8080561A HU56180A HU179836B HU 179836 B HU179836 B HU 179836B HU 8080561 A HU8080561 A HU 8080561A HU 56180 A HU56180 A HU 56180A HU 179836 B HU179836 B HU 179836B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- hydrogen
- salt
- dehydro
- phenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 15
- 230000008569 process Effects 0.000 title claims description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 150000001875 compounds Chemical class 0.000 claims abstract description 35
- 239000001257 hydrogen Substances 0.000 claims abstract description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims abstract description 18
- 239000002168 alkylating agent Substances 0.000 claims abstract description 11
- 229940100198 alkylating agent Drugs 0.000 claims abstract description 11
- 239000012458 free base Substances 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- 239000011541 reaction mixture Substances 0.000 claims description 20
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 229960000583 acetic acid Drugs 0.000 claims description 11
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000012362 glacial acetic acid Substances 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 239000012279 sodium borohydride Substances 0.000 claims description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims 1
- 230000000171 quenching effect Effects 0.000 claims 1
- UGKSITLWMZJTHC-UHFFFAOYSA-N tribromo-$l^{3}-bromane Chemical compound BrBr(Br)Br UGKSITLWMZJTHC-UHFFFAOYSA-N 0.000 claims 1
- -1 1,2,5, 6-tetrahydro-4-phenylpyridine compound Chemical class 0.000 abstract description 15
- 230000000202 analgesic effect Effects 0.000 abstract description 8
- 239000002585 base Substances 0.000 abstract description 7
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 abstract description 5
- 150000001450 anions Chemical class 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 1
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- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
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- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 6
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- 238000005804 alkylation reaction Methods 0.000 description 5
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- 229960005181 morphine Drugs 0.000 description 5
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- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
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- 238000004821 distillation Methods 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- OMPXTQYWYRWWPH-UHFFFAOYSA-N 4-phenyl-1,2,3,6-tetrahydropyridine Chemical class C1NCCC(C=2C=CC=CC=2)=C1 OMPXTQYWYRWWPH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
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- UCEXMJMSILZCHZ-UHFFFAOYSA-N 2-[(4-butoxybenzoyl)amino]acetic acid Chemical compound CCCCOC1=CC=C(C(=O)NCC(O)=O)C=C1 UCEXMJMSILZCHZ-UHFFFAOYSA-N 0.000 description 1
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- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 238000009115 maintenance therapy Methods 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 230000037040 pain threshold Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940065347 propoxyphene hydrochloride Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 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
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C07D221/26—Benzomorphans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1952779A | 1979-03-12 | 1979-03-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU179836B true HU179836B (en) | 1982-12-28 |
Family
ID=21793680
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU8080561A HU179836B (en) | 1979-03-12 | 1980-03-10 | Process for producing phenyl-morphane derivatives |
Country Status (11)
| Country | Link |
|---|---|
| EP (2) | EP0059989A1 (enExample) |
| JP (1) | JPS55124768A (enExample) |
| KR (1) | KR830001900A (enExample) |
| BE (1) | BE882152A (enExample) |
| CA (1) | CA1148150A (enExample) |
| FR (1) | FR2451368A1 (enExample) |
| GB (2) | GB2045248B (enExample) |
| HU (1) | HU179836B (enExample) |
| IL (1) | IL59553A0 (enExample) |
| IT (1) | IT1129740B (enExample) |
| LU (1) | LU82235A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0652811B2 (ja) * | 1984-07-04 | 1994-07-06 | 松下電器産業株式会社 | 高電圧発生装置 |
| US5087214A (en) * | 1991-05-21 | 1992-02-11 | United Technologies Automotive, Inc. | Battery terminal connector |
| US6900228B1 (en) | 1998-03-10 | 2005-05-31 | Research Triangle Institute | Opiate compounds, methods of making and methods of use |
| CA2324418C (en) * | 1998-03-10 | 2010-02-02 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| AU2572800A (en) | 1999-02-18 | 2000-09-04 | Hisamitsu Pharmaceutical Co. Inc. | Morphan derivatives or salts thereof and medicinal compositions containing the same |
| TW200306189A (en) | 2002-03-21 | 2003-11-16 | Merz Pharma Gmbh & Co Kgaa | Azabicyclic, azatricyclic and azaspirocyclic derivatives of aminocyclohexane NMDA, 5HT3, and neuronal nicotinic receptor antagonists |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR206937A1 (es) * | 1974-09-06 | 1976-08-31 | Lilly Co Eli | Procedimiento para preparar compuestos de 1-sustituido-4-alquil-4-fenil-piperidina |
-
1980
- 1980-03-07 IL IL59553A patent/IL59553A0/xx unknown
- 1980-03-07 FR FR8005179A patent/FR2451368A1/fr active Granted
- 1980-03-10 BE BE1/9743A patent/BE882152A/fr not_active IP Right Cessation
- 1980-03-10 HU HU8080561A patent/HU179836B/hu unknown
- 1980-03-10 IT IT20473/80A patent/IT1129740B/it active
- 1980-03-10 CA CA000347364A patent/CA1148150A/en not_active Expired
- 1980-03-10 LU LU82235A patent/LU82235A1/fr unknown
- 1980-03-11 EP EP82102714A patent/EP0059989A1/en not_active Ceased
- 1980-03-11 JP JP3256680A patent/JPS55124768A/ja active Pending
- 1980-03-11 GB GB8008172A patent/GB2045248B/en not_active Expired
- 1980-03-11 EP EP80300746A patent/EP0018077A3/en not_active Ceased
- 1980-03-12 KR KR1019800001021A patent/KR830001900A/ko not_active Ceased
-
1982
- 1982-09-23 GB GB08227192A patent/GB2111976B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2045248B (en) | 1983-05-05 |
| CA1148150A (en) | 1983-06-14 |
| IT1129740B (it) | 1986-06-11 |
| KR830001900A (ko) | 1983-05-19 |
| EP0059989A1 (en) | 1982-09-15 |
| EP0018077A2 (en) | 1980-10-29 |
| GB2111976A (en) | 1983-07-13 |
| GB2045248A (en) | 1980-10-29 |
| FR2451368B1 (enExample) | 1983-03-18 |
| IL59553A0 (en) | 1980-06-30 |
| GB2111976B (en) | 1983-11-09 |
| FR2451368A1 (fr) | 1980-10-10 |
| IT8020473A0 (it) | 1980-03-10 |
| LU82235A1 (fr) | 1980-06-06 |
| JPS55124768A (en) | 1980-09-26 |
| EP0018077A3 (en) | 1980-11-26 |
| BE882152A (fr) | 1980-09-10 |
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