CH498803A - 1-bopropyl amino 2-hydroxy-3-(2' isopropoxy - phenoxy) propane and salts with phareological - Google Patents
1-bopropyl amino 2-hydroxy-3-(2' isopropoxy - phenoxy) propane and salts with phareologicalInfo
- Publication number
- CH498803A CH498803A CH1232770A CH1232770A CH498803A CH 498803 A CH498803 A CH 498803A CH 1232770 A CH1232770 A CH 1232770A CH 1232770 A CH1232770 A CH 1232770A CH 498803 A CH498803 A CH 498803A
- Authority
- CH
- Switzerland
- Prior art keywords
- propane
- salts
- hydroxy
- isopropoxy
- phenoxy
- Prior art date
Links
- 150000003839 salts Chemical class 0.000 title claims abstract description 19
- XFXYEKNMJKVAMS-UHFFFAOYSA-N 1-amino-3-(2-propan-2-yloxyphenoxy)propan-2-ol Chemical compound C(C)(C)OC1=C(OCC(CN)O)C=CC=C1 XFXYEKNMJKVAMS-UHFFFAOYSA-N 0.000 title 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 11
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- YDOOFGNGBOQBCC-UHFFFAOYSA-N 1-(propan-2-ylamino)-3-(2-propan-2-yloxyphenoxy)propan-2-ol Chemical compound CC(C)NCC(O)COC1=CC=CC=C1OC(C)C YDOOFGNGBOQBCC-UHFFFAOYSA-N 0.000 claims description 6
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000001118 alkylidene group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- 230000001419 dependent effect Effects 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract description 12
- SNVXAAGRJNDUPV-UHFFFAOYSA-N 3-amino-4-methyl-1-(2-propan-2-yloxyphenoxy)pentan-2-ol Chemical compound C(C)(C)C(C(COC1=C(C=CC=C1)OC(C)C)O)N SNVXAAGRJNDUPV-UHFFFAOYSA-N 0.000 abstract description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 125000002252 acyl group Chemical group 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- -1 propylamino-2-hydroxy-3 - (2'-isopropoxy-phenoxy) -propane Chemical compound 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- FZKCAHQKNJXICB-UHFFFAOYSA-N 2,1-benzoxazole Chemical compound C1=CC=CC2=CON=C21 FZKCAHQKNJXICB-UHFFFAOYSA-N 0.000 description 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000208011 Digitalis Species 0.000 description 1
- 206010015856 Extrasystoles Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000000418 Premature Cardiac Complexes Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Emergency Medicine (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
1-Isopropyl-amino-2-hydroxy-3-(2'-isopropoxyphenoxy)propane and salts with pharmacological props. The patent is similar to CH 498083 except that the cpd. is prod. by hydrolysing or hydrogenolysing a deriv. contg. a separable gp. at the N atom or the 2-OH position (e.g. arylalkyl or acyl) or a bridge between these posns. In an example, 3-isopropyl-5-(2'-isopropoxyphenoxymethyl)-oxazolidinone-(2) is hydrolysed with NaOH.
Description
Verfahren zur Herstellung des neuen 1-Isopropyl-amino-2-hydroxy-3- (2'-isopropoxy- phenoxy)-propans und seiner Salze
Gegenstand der Erfindung ist ein Verfahren zur Herstellung des l-Isopropylamino-2-hydroxy-3-(2'-iso- propoxy-phenoxy)-propans der Formel
EMI1.1
Die neue Verbindung besitzt wertvolle pharmakologische Eigenschaften. Insbesondere bewirkt sie eine Hemmung adrenergischer p-Rezeptoren. So hemmt sie z. B. an der mit Dial narkotisierten Katze oder am wachen Hund durch Isoproterenol hervorgerufene Blutdrucksenkungen in Dosen von 0,01-1 mg/kg i. v. oder 2-3 mg/kg p. o. Sie ist in der Lage, Digitalis-induzierte Extrasystolen zu unterdrücken, wie z. B. aus Experimenten mit einer Dosis von 0,3-1 mg/kg i. v. am narkotisierten Hund hervorgeht.
Die Verbindung kann dementsprechend bei Herz- und Kreislauferkrankungen als Medikament angewendet werden.
Das erfindungsgemässe Verfahren zur Herstellung der neuen Verbindung ist dadurch gekennzeichnet, dass man in einem 1 -I & propylamino-2-hydroy-3 -(2'-iso- propoxy-phenoxy)-propan oder einem Salz davon, das am Stickstoffatom und an der 2-Hydroxylgruppe je einen einwertigen oder zusammen einen zweiwertigen durch Hydrolyse oder Hydrogenolyse abspaltbaren Rest aufweist, diese durch Hydrolyse oder Hydrogenolyse abspaltet. Solche Reste sind z. B. a-Arylalkylreste, wie ein Benzylrest, Oxycarbonylreste, wie der Benzyloxycarbonylrest oder der tert.-Butoxycarbonylrest, oder Acylreste von Carbonsäure, wie niedere Alkanoylreste, z. B. der Acetylrest. Verbindungen mit durch Hydrolyse abspaltbaren zweiwertigen Resten sind z. B. die der Formel a)
EMI1.2
worin X' für die Carbonylgruppe oder für eine Alkylidengruppe steht.
Die Hydrolyse und Hydrogenolyse werden in üblicher Weise, letztere besonders mit katalytischer Hydrierung, vorgenommen. Die Hydrolyse einer Verbindung der Formel a), worin X' für eine Alkylidengruppe steht, wird in saurer Lösung durchgeführt.
Die Ausgangsstoffe sind bekannt oder können nach an sich bekannten Methoden gewonnen werden.
Je nach den Verfahrensbedingungeri und Ausgangsstoffen erhält man den Endstoff in freier Form oder in der ebenfalls in der Erfindung inbegriffenen Form seiner Salze. Die Salze des Endstoffs können in an sich bekannter Weise, z. B. mit Alkalien oder Ionenaustauschern in die freie Base übergeführt werden. Von der letzteren lassen sich durch Umsetzung mit organischen oder anorganischen Säuren, insbesondere solchen, die zur Bildung von therapeutisch verwendbaren Salzen geeignet sind, Salze gewinnen.
Als solche Säuren seien beispielsweise genannt: Halogeliwasserstoffsäuren, Schwefelsäuren, Phosphorsäure, Salpetersäure, Perchlorsäure, aliphatische, alicyclische, aromatische oder heterocyclische Carbon- oder Sulfonsäure, wie Ameisen-, Essig-, Propion-, Bernstein-, Glykol-, Milch-, Äpfel-, Wein-, Zitronen-, Ascorbin-, Malein-, Hydroxymaleinoder Brenztraubensäure; Phenylessig-, Benzoe-, P Aminobenzoe-, Anthranil-, p-Hydroxybenzoe-, Salicyloder p-Aminosalicylsäure, Embonsäure, Methansulfon-, Athansulfon-, Hydroxyäthansulfon-, Athylensulfons äure; Halogenbenzolsulfon-, Toluolsulfon-, Naphthalinsulfonsäure oder Sulfamilsäure, Methionin, Tryptophan, Lysin oder Arginin.
Diese oder andere Salze der neuen Verbindung, wie z. B. die Pikrate, können auch zur Reinigung der erhaltenen freien Base dienen, indem man die freie Base in Salze überführt, diese abtrennt und aus den Salzen wiederum die Base freimacht. Infolge der engen Beziehungen zwischen der neuen Verbindung in freier Form und in Form ihrer Salze sind im vorausgegangenen und nachfolgend unter der freien Base sinnund zweckmässig, gegebenenfalls auch die entsprechenden Salze zu verstehen.
Die Erfindung betrifft auch diejenigen Ausführungsformen des Verfahrens, nach denen man einen Ausgangsstoff in Form eines unter den Reaktionsbedingungen gebildeten rohen Gemisches oder in Form eines Salzes verwendet.
Die neue Verbindung kann als Racemat oder in Form der Antipoden vorliegen. Das Racemat lässt sich in üblicher Weise in die Antipoden zerlegen.
Die neue Verbindung kann z. B. in Form pharmazeutischer Präparate Verwendung finden, welche sie in freier Form oder gegebenenfalls in Form ihrer Salze in Mischung mit einem für die enterale oder parenterale Applikation geeigneten pharmazeutischen organischen oder anorganischen, festen oder flüssigen Trägermaterial enthalten.
In den folgenden Beispielen sind die Temperaturen in Celsiusgraden angegeben.
Beispiel 1
10,0 g 3 -Isopropyl-5-(2'-isopropoxy-phenoxyme- thyl)-oxazolidinon-(2) werden mit 50 ml 10-n Natronlauge während 15 Minuten unter gutem Rühren auf 1200 erhitzt. Hierauf gibt man 200 ml Wasser zu und extrahiert mit Äther. Die Äther-Schicht wird abgetrennt, getrocknet und im Wasserstrahlvakuum eingedampft.
Es verbleibt das 1-Isopropylamino-2-hydroxy-3-(2'so propoxy-phenoxy)-propan der Formel
EMI2.1
das nach Umkristallisation aus Essigester/Petroläther bei 60-61 schmilzt. Das Hydrochlorid schmilzt bei 129-130 .
Beispiel 2
1 g 1-(N-Acetyl-isopropylamino)-2-acetoxy-3-(2'- isopropoxy-phenexy)-propan wird in 7 ml absolutem Alkohol und 3,5 ml 5n Natronlauge während 7 Stunden unter Rückfluss gekocht. Die Reaktionslösung wird im Vakuum eingeengt. Den Eindampfrückstand versetzt man mit Wasser und schüttelt mit Äther aus. Nach Eindampfen der getrockneten Ätherlösung erhält man als Rückstand das 1-Isopropylamino-2-hydroxy-3-(2'isopropoxy-phenoxy)-propan der Formel
EMI2.2
dessen Hydrochlorid bei 129-1300 schmilzt.
Beispiel 3
Zu einer Lösung von 5,0 g 3 -Isopropyl-5-(2'-iso- propoxy-phenoxymethyl)-oxazolidin in 50 ml Äthanol gibt man 25 ml 2n Salzsäure und erwärmt eine Stunde auf 700. Anschliessend wird der Alkohol abdestilliert und den Rückstand versetzt man mit 75 ml 2n Natronlauge. Es scheidet sich ein Öl ab, das mit Äther extrahiert wird. Nach dem Trocknen und Eindampfen des äther bleibt das 1-Isopropylamino-2-hydroxy-3-(2'-isopropoxy-phenoxy)-propan der Formel
EMI2.3
dessen Hydrochlorid bei 129-130 schmilzt, zurück.
Process for the preparation of the new 1-isopropyl-amino-2-hydroxy-3- (2'-isopropoxyphenoxy) propane and its salts
The invention relates to a process for the preparation of l-isopropylamino-2-hydroxy-3- (2'-isopropoxy-phenoxy) -propane of the formula
EMI1.1
The new compound has valuable pharmacological properties. In particular, it has the effect of inhibiting adrenergic p-receptors. So it inhibits z. B. in the cat anesthetized with Dial or in the conscious dog caused by isoproterenol lowering blood pressure in doses of 0.01-1 mg / kg i. v. or 2-3 mg / kg p. o. It is able to suppress digitalis-induced extrasystoles, such as B. from experiments with a dose of 0.3-1 mg / kg i. v. on the anesthetized dog.
The compound can accordingly be used as a medicament for heart and circulatory diseases.
The inventive method for the preparation of the new compound is characterized in that in a 1 -I & propylamino-2-hydroxy-3 - (2'-isopropoxy-phenoxy) -propane or a salt thereof, which is on the nitrogen atom and on of the 2-hydroxyl group each has a monovalent or together a bivalent radical which can be split off by hydrolysis or hydrogenolysis, which is split off by hydrolysis or hydrogenolysis. Such residues are e.g. B. a-Arylalkyl radicals, such as a benzyl radical, oxycarbonyl radicals, such as the benzyloxycarbonyl radical or the tert-butoxycarbonyl radical, or acyl radicals of carboxylic acid, such as lower alkanoyl radicals, e.g. B. the acetyl radical. Compounds with divalent radicals which can be split off by hydrolysis are, for. B. those of the formula a)
EMI1.2
wherein X 'stands for the carbonyl group or for an alkylidene group.
The hydrolysis and hydrogenolysis are carried out in the usual way, the latter especially with catalytic hydrogenation. The hydrolysis of a compound of the formula a) in which X 'stands for an alkylidene group is carried out in acidic solution.
The starting materials are known or can be obtained by methods known per se.
Depending on the process conditions and starting materials, the end product is obtained in free form or in the form of its salts, which is also included in the invention. The salts of the end product can in a conventional manner, for. B. be converted into the free base with alkalis or ion exchangers. Salts can be obtained from the latter by reaction with organic or inorganic acids, in particular those which are suitable for the formation of therapeutically useful salts.
Examples of such acids are: hydrohalic acids, sulfuric acids, phosphoric acid, nitric acid, perchloric acid, aliphatic, alicyclic, aromatic or heterocyclic carboxylic or sulfonic acids, such as formic, acetic, propionic, succinic, glycolic, lactic, apple , Tartaric, citric, ascorbic, maleic, hydroxymaleic or pyruvic acid; Phenylacetic, benzoic, P aminobenzoic, anthranil, p-hydroxybenzoic, salicylic or p-aminosalicylic acid, emboxylic acid, methanesulphonic, ethanesulphonic, hydroxyethanesulphonic, ethylene sulphonic acid; Halobenzenesulfonic, toluenesulfonic, naphthalenesulfonic or sulfamilic acid, methionine, tryptophan, lysine or arginine.
These or other salts of the new compound, such as. B. the picrates, can also be used to purify the free base obtained by converting the free base into salts, separating them and in turn frees the base from the salts. As a result of the close relationships between the new compound in free form and in the form of its salts, in the preceding and in the following the term “free base” is meaningful and expedient, if appropriate also to mean the corresponding salts.
The invention also relates to those embodiments of the process in which a starting material is used in the form of a crude mixture formed under the reaction conditions or in the form of a salt.
The new compound can be present as a racemate or in the form of the antipodes. The racemate can be broken down into the antipodes in the usual way.
The new connection can e.g. B. in the form of pharmaceutical preparations are used which they contain in free form or optionally in the form of their salts in a mixture with a pharmaceutical organic or inorganic, solid or liquid carrier material suitable for enteral or parenteral administration.
In the following examples the temperatures are given in degrees Celsius.
example 1
10.0 g of 3-isopropyl-5- (2'-isopropoxyphenoxymethyl) -oxazolidinone- (2) are heated to 1200 with 50 ml of 10N sodium hydroxide solution for 15 minutes with thorough stirring. 200 ml of water are then added and the mixture is extracted with ether. The ether layer is separated off, dried and evaporated in a water jet vacuum.
There remains the 1-isopropylamino-2-hydroxy-3- (2'so propoxy-phenoxy) -propane of the formula
EMI2.1
which, after recrystallization from ethyl acetate / petroleum ether, melts at 60-61. The hydrochloride melts at 129-130.
Example 2
1 g of 1- (N-acetyl-isopropylamino) -2-acetoxy-3- (2'-isopropoxy-phenexy) -propane is refluxed in 7 ml of absolute alcohol and 3.5 ml of 5N sodium hydroxide solution for 7 hours. The reaction solution is concentrated in vacuo. The evaporation residue is mixed with water and extracted with ether. After evaporating the dried ether solution, the residue obtained is 1-isopropylamino-2-hydroxy-3- (2'isopropoxyphenoxy) propane of the formula
EMI2.2
its hydrochloride melts at 129-1300.
Example 3
25 ml of 2N hydrochloric acid are added to a solution of 5.0 g of 3-isopropyl-5- (2'-isopropoxy-phenoxymethyl) -oxazolidine in 50 ml of ethanol and the mixture is heated to 700 for one hour. The alcohol is then distilled off and the 75 ml of 2N sodium hydroxide solution are added to the residue. An oil separates which is extracted with ether. After drying and evaporation of the ether, the 1-isopropylamino-2-hydroxy-3- (2'-isopropoxy-phenoxy) -propane of the formula remains
EMI2.3
whose hydrochloride melts at 129-130.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1232770A CH498803A (en) | 1965-08-05 | 1965-08-05 | 1-bopropyl amino 2-hydroxy-3-(2' isopropoxy - phenoxy) propane and salts with phareological |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1103365A CH497378A (en) | 1965-08-05 | 1965-08-05 | 1-isopropylamino-2-hydroxy-3-(2'-isopropoxy- - phenoxy)-propane, pharmaceutical used in |
| CH1232770A CH498803A (en) | 1965-08-05 | 1965-08-05 | 1-bopropyl amino 2-hydroxy-3-(2' isopropoxy - phenoxy) propane and salts with phareological |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH498803A true CH498803A (en) | 1970-11-15 |
Family
ID=4369370
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1232770A CH498803A (en) | 1965-08-05 | 1965-08-05 | 1-bopropyl amino 2-hydroxy-3-(2' isopropoxy - phenoxy) propane and salts with phareological |
| CH1103365A CH497378A (en) | 1964-10-14 | 1965-08-05 | 1-isopropylamino-2-hydroxy-3-(2'-isopropoxy- - phenoxy)-propane, pharmaceutical used in |
| CH1232870A CH498083A (en) | 1965-08-05 | 1965-08-05 | 1-isopropyl-amino-2-hydroxy-3-(2'-ispropoxy - phenoxy) propane and salts with pharmacolo |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1103365A CH497378A (en) | 1964-10-14 | 1965-08-05 | 1-isopropylamino-2-hydroxy-3-(2'-isopropoxy- - phenoxy)-propane, pharmaceutical used in |
| CH1232870A CH498083A (en) | 1965-08-05 | 1965-08-05 | 1-isopropyl-amino-2-hydroxy-3-(2'-ispropoxy - phenoxy) propane and salts with pharmacolo |
Country Status (2)
| Country | Link |
|---|---|
| AT (1) | AT266082B (en) |
| CH (3) | CH498803A (en) |
-
1965
- 1965-08-05 CH CH1232770A patent/CH498803A/en not_active IP Right Cessation
- 1965-08-05 CH CH1103365A patent/CH497378A/en not_active IP Right Cessation
- 1965-08-05 CH CH1232870A patent/CH498083A/en not_active IP Right Cessation
- 1965-10-13 AT AT225767A patent/AT266082B/en active
Also Published As
| Publication number | Publication date |
|---|---|
| AT266082B (en) | 1968-11-11 |
| CH497378A (en) | 1970-10-15 |
| CH498083A (en) | 1970-10-31 |
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| Date | Code | Title | Description |
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| PL | Patent ceased |