NO115388B - - Google Patents
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- Publication number
- NO115388B NO115388B NO15964965A NO15964965A NO115388B NO 115388 B NO115388 B NO 115388B NO 15964965 A NO15964965 A NO 15964965A NO 15964965 A NO15964965 A NO 15964965A NO 115388 B NO115388 B NO 115388B
- Authority
- NO
- Norway
- Prior art keywords
- propane
- allyloxy
- hydroxy
- phenoxy
- isopropylamino
- Prior art date
Links
- 239000001294 propane Substances 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 14
- FTJSDHRLVNMSLN-UHFFFAOYSA-N 1-(propan-2-ylamino)-3-(4-prop-2-enoxyphenoxy)propan-2-ol Chemical compound CC(C)NCC(O)COC1=CC=C(OCC=C)C=C1 FTJSDHRLVNMSLN-UHFFFAOYSA-N 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- FNEJKCGACRPXBT-UHFFFAOYSA-N 2-prop-2-enoxyphenol Chemical compound OC1=CC=CC=C1OCC=C FNEJKCGACRPXBT-UHFFFAOYSA-N 0.000 claims description 4
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 4
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- AQFROTXMDPNEJE-UHFFFAOYSA-N n-(oxiran-2-ylmethyl)propan-2-amine Chemical compound CC(C)NCC1CO1 AQFROTXMDPNEJE-UHFFFAOYSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- YKBZGEJJKPNRSI-UHFFFAOYSA-N 3-(propan-2-ylamino)propane-1,2-diol Chemical compound CC(C)NCC(O)CO YKBZGEJJKPNRSI-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000000155 melt Substances 0.000 description 11
- -1 halogen hydrogen Chemical class 0.000 description 10
- 235000011121 sodium hydroxide Nutrition 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000002253 acid Substances 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 229940072033 potash Drugs 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 235000015320 potassium carbonate Nutrition 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000009835 boiling Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 238000009833 condensation Methods 0.000 description 4
- 230000005494 condensation Effects 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000003054 catalyst Substances 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
- 238000001035 drying Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- BZVHVRVBYPQBCI-UHFFFAOYSA-N 2-(3-amino-2-hydroxypropoxy)phenol Chemical compound NCC(O)COC1=CC=CC=C1O BZVHVRVBYPQBCI-UHFFFAOYSA-N 0.000 description 2
- XGRBWRAZMPDZPQ-UHFFFAOYSA-N 2-[(2-phenylmethoxyphenoxy)methyl]oxirane Chemical compound C1OC1COC1=CC=CC=C1OCC1=CC=CC=C1 XGRBWRAZMPDZPQ-UHFFFAOYSA-N 0.000 description 2
- CCZCXFHJMKINPE-UHFFFAOYSA-N 2-phenylmethoxyphenol Chemical compound OC1=CC=CC=C1OCC1=CC=CC=C1 CCZCXFHJMKINPE-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- 125000005336 allyloxy group Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ZRBLAFWOGCBZPV-UHFFFAOYSA-N 1-chloro-3-(propan-2-ylamino)propan-2-ol Chemical compound CC(C)NCC(O)CCl ZRBLAFWOGCBZPV-UHFFFAOYSA-N 0.000 description 1
- KUBDPQJOLOUJRM-UHFFFAOYSA-N 2-(chloromethyl)oxirane;4-[2-(4-hydroxyphenyl)propan-2-yl]phenol Chemical compound ClCC1CO1.C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 KUBDPQJOLOUJRM-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-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
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000208011 Digitalis Species 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 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 class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000000418 Premature Cardiac Complexes Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [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
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- XENVCRGQTABGKY-ZHACJKMWSA-N chlorohydrin Chemical compound CC#CC#CC#CC#C\C=C\C(Cl)CO XENVCRGQTABGKY-ZHACJKMWSA-N 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 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
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 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
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 235000019260 propionic acid Nutrition 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
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 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
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/24—Ethers with hydroxy compounds containing no oxirane rings with polyhydroxy compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/24—Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
Description
Fremgangsmåte til fremstilling av den nye terapeutisk virksomme 1-iso-propyl-amino-2: Process for the production of the new therapeutically effective 1-iso-propyl-amino-2:
hydroksy-3- (o-allyloksy-fenoksy)-propan.hydroxy-3-(o-allyloxy-phenoxy)-propane.
Gjenstanden, for foreliggende oppfinnelse er The object of the present invention is
fremstilling av den nye terapeutisk virksomme 1-isopropylamino-2-hydroksy-3-(o-allyloksy-fenoksy) propan med formelen preparation of the new therapeutically effective 1-isopropylamino-2-hydroxy-3-(o-allyloxy-phenoxy) propane with the formula
og dens salter. and its salts.
Den nye forbindelse har verdifulle farma-kologiske egenskaper. Særlig bevirker den en The new compound has valuable pharmacological properties. In particular, it causes a
hemning av adrenergiske p-reseptorer. Således inhibition of adrenergic β-receptors. Thus
hemmer den f. eks. med doser på 0,01—1 mg/kg inhibits it, e.g. with doses of 0.01-1 mg/kg
intravenøst eller 2—3 mg/kg p.o. blodtrykksenk-ninger som er fremkalt med dial på narkotiserte intravenously or 2-3 mg/kg p.o. blood pressure reductions induced by dial in narcotized patients
katter eller voksne hunder. Den er i stand til å undertrykke digitalis-induserte ekstra systoler, slik som f. eks. fra eksperimenter med en dose på 0,3—1 mg/kg intravenøst hos en narkotisert hund. Forbindelsen kan således anvendes ved hjerte og kretsløpssykdommer. cats or adult dogs. It is capable of suppressing digitalis-induced extra systole, such as e.g. from experiments with a dose of 0.3-1 mg/kg intravenously in an anesthetized dog. The compound can thus be used for heart and circulatory diseases.
Den nye forbindelse fremstilles etter i og The new compound is produced according to and
for seg kjente fremgangsmåter.methods known per se.
A. Hensiktsmessig omsetter man en 3-(o-allyloksyfenoksy) -1,2-dihydroksy-propan eller 3- (o-allyloksy-fenoksy) -1,2-epoksy-propan som er forestret reaksjonsdyktig ved hydroksylgruppen i 1-stilling med isopropylamin. En reaksjonsdyktig ester er derved f. eks. slike fra en sterk organisk eller anorganisk syre, slik som fremfor alt en halogenhydrogensyre, f. eks. klor-, brom-eller jodhydrogensyre eller en sulfonsyre slik som arylsulfonsyre, f. eks. p-toluolsulfonsyre. Reaksjonen utføres på vanlig måte ved anven-deise av en reaksjonsdyktig ester, fortrinnsvis i nærvær av et basisk kondensasjonsmiddel eller et overskudd av amin, eller A. A 3-(o-allyloxyphenoxy)-1,2-dihydroxy-propane or 3-(o-allyloxy-phenoxy)-1,2-epoxy-propane which is reactively esterified at the hydroxyl group in the 1-position is suitably reacted with isopropylamine. A reactive ester is thereby e.g. such from a strong organic or inorganic acid, such as above all a halogen hydrogen acid, e.g. hydrochloric, bromic or hydroiodic acid or a sulphonic acid such as arylsulphonic acid, e.g. p-toluenesulfonic acid. The reaction is carried out in the usual way by using a reactive ester, preferably in the presence of a basic condensation agent or an excess of amine, or
B. man innfører isopropylresten i aminogruppen i l-amino-2-hydroksy-3-(o-allyloksy-fenoksy) -propan. Dette skjer på vanlig måte, hensiktsmessig ved omsetning med en reaksjonsdyktig ester, f. eks. med en av de ovenfor nevnte syrer, fremfor alt med en halogenhydrogensyre av isopropanol. Ved reaksjonen med den reak-sjonsdyktige ester anvender man fortrinnsvis et basiskondensasjonsmiddel eller et overskudd av amin, eller B. one introduces the isopropyl residue in the amino group of 1-amino-2-hydroxy-3-(o-allyloxy-phenoxy)-propane. This happens in the usual way, suitably by reaction with a reactive ester, e.g. with one of the above-mentioned acids, above all with a halohydrogen acid of isopropanol. In the reaction with the reactive ester, a basic condensation agent or an excess of amine is preferably used, or
C. Videre kan man omsette o-allyloksyfenol med en i hydroksylgruppen i 1-stilling reaksjonsdyktig forestret 3-isopropylamino-l,2-dihydro-oksypropan, f. eks. en av de ovenfor nevnte este-re, særlig et halogenid, eller med 3-isopropyl-amino-l,2-epoksy-propan. Derved arbeider man på vanlig måte. Ved anvendelse av esterene går man frem hensiktsmessig i nærvær av et syre-bindende kondensasjonsmiddel, særlig et kondensasjonsmiddel som er egnet til saltdannelse med fenolen, eller man anvender et metall slik som alkalisalt av fenol. Således kan man arbeide i nærvær av alkalialkoholater, eller D. i l-isoproylamino-2-hydroksy-3-(o-allyl-oksyfenoksy)-propaner som ved nitrogenatomet og/eller ved 2-hydroksylgruppen oppviser en rest som kan avspaltes ved hydrolyse eller hydrogenolyse, ayspalter man denne. Slike rester er f. eks. a-arylalkylrester, slik som en benzylrest, oksykarbonylrester, slik som benzyloksykarbonyl-resten eller den tertiære butoksykarbonylrest, eller acylrester av karbonsyrer slik som lavere alkanoylrester, f. eks. acetylresten. Forbindelser med rester som kan avspaltes ved hydrolyse er f. eks. forbindelser med formel a) C. Furthermore, one can react o-allyloxyphenol with a reactive esterified 3-isopropylamino-1,2-dihydro-oxypropane in the hydroxyl group in the 1-position, e.g. one of the above-mentioned esters, especially a halide, or with 3-isopropyl-amino-1,2-epoxy-propane. Thereby, you work in the usual way. When using the esters, one proceeds appropriately in the presence of an acid-binding condensing agent, in particular a condensing agent which is suitable for salt formation with the phenol, or one uses a metal such as an alkali salt of phenol. Thus, one can work in the presence of alkali alcoholates, or D. in l-isopropylamino-2-hydroxy-3-(o-allyl-oxyphenoxy)-propanes which at the nitrogen atom and/or at the 2-hydroxyl group exhibit a residue that can be split off by hydrolysis or hydrogenolysis, this is split. Such residues are e.g. α-arylalkyl residues, such as a benzyl residue, oxycarbonyl residues, such as the benzyloxycarbonyl residue or the tertiary butoxycarbonyl residue, or acyl residues of carboxylic acids such as lower alkanoyl residues, e.g. the acetyl residue. Compounds with residues that can be split off by hydrolysis are e.g. compounds of formula a)
hvor X' betyr karbonylgruppen eller en alkylidengruppe. Hydrolysen og hydrogenolysen utføres på vanlig måte, den siste særlig med katalytisk hydrering under hensyntagen til allyloksygruppen. Hydrolyse av en forbindelse med formel a) hvor X' betyr en alkylidengruppe utføres i sur opp-løsning, eller E. at man i en forbindelse med formelen where X' means the carbonyl group or an alkylidene group. The hydrolysis and hydrogenolysis are carried out in the usual way, the latter in particular with catalytic hydrogenation taking into account the allyloxy group. Hydrolysis of a compound of formula a) where X' means an alkylidene group is carried out in acidic solution, or E. that in a compound of the formula
hvori Y er en rest som ved reduksjon av en C = N-dobbeltbinding kan overføres til gruppen in which Y is a residue which, by reduction of a C = N double bond, can be transferred to the group
reduserer azomethinbindingen. Resten Y er fremfor alt resten med formel reduces azomethine binding. The remainder Y is above all the remainder with formula
Reduksjonen kan foretas på vanlig måte f. eks. med di-lettmetallhydrider, slik som litium-aluminiumhydrid eller natriumborhydrid eller med katalytisk hydrering, f. eks. med palladium, platinoksyd eller raney-nikkel som katalysator. Derved må det imidlertid tas hensyn til at allyloksygruppen ikke angripes. The reduction can be made in the usual way, e.g. with di-light metal hydrides, such as lithium aluminum hydride or sodium borohydride or with catalytic hydrogenation, e.g. with palladium, platinum oxide or Raney nickel as catalyst. Thereby, however, care must be taken to ensure that the allyloxy group is not attacked.
Man kan imidlertid gå frem således at man f. eks. omsetter 3-(o-allyloksyfenoksy)-hydroksy-propylamin med aceton i nærvær av et egnet reduksjonsmiddel, fortrinnsvis av de ovennevnte, idet det intermediært oppstår de ovenfor viste Schiffske baser hvis isolering imidlertid over-flødiggjøres. You can, however, proceed in such a way that you e.g. reacts 3-(o-allyloxyphenoxy)-hydroxy-propylamine with acetone in the presence of a suitable reducing agent, preferably one of the above, the Schiff bases shown above being intermediately produced, the isolation of which, however, is made redundant.
Alt etter fremgangsmåtebetingelsene og utgangsstoffene får man et produkt i fri form eller Depending on the process conditions and starting materials, a product is obtained in free form or
i form av sine salter som også er produkt frem-stilt ifølge oppfinnelsen. Saltene av sluttprodukt-ene kan på i og for seg kjent måte overføres til en fri base, f. eks. med alkali eller ioneutveksler. in the form of its salts, which are also products produced according to the invention. The salts of the end products can be transferred in a manner known per se to a free base, e.g. with alkali or ion exchanger.
Av de siste kan det fremstilles salter ved omsetning med organiske eller anorganiske syrer, særlig slike som er egnet til dannelse av terapeutisk anvendelige salter. Som slike syrer skal f. eks. nevnes: Halogenhydrogensyrer, svovelsyrer, fos-forsyrer, salpetersyrer, perklorsyrer, alifatiske, alicykliske, aromatiske eller heterocykliske kar-bon- eller sulfonsyrer slik som maursyre, eddik-syre, propionsyre, ravsyre, glykolsyre, melkesyre, eplesyre, vinsyre, sitronsyre, ascorbinsyre, ma-leinsyre, hydroksymaleinsyre eller pyrodruesyre, fenyleddiksyre, benzoesyre, p-aminobenzosyre, antranilsyre, p-hydrobenzosyre, salisylsyre eller p-aminosalisylsyre, embonsyre, metansulfonsyre, etansulfonsyre, hydroksyetansulfonsyre, etylen-sulfonsyre, halogenbenzolsulfonsyre, toluolsulfonsyre, naftalinsulfonsyre eller sulfanilsyre, metionin, tryptofan, lysin eller aginin. Of the latter, salts can be prepared by reaction with organic or inorganic acids, especially those which are suitable for the formation of therapeutically applicable salts. As such acids, e.g. mentioned: Hydrohalic acids, sulfuric acids, phosphoric acids, nitric acids, perchloric acids, aliphatic, alicyclic, aromatic or heterocyclic carboxylic or sulfonic acids such as formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid . , tryptophan, lysine or aginine.
Disse eller andre salter av den nye forbindelse slik som f. eks. pikrater, kan også tjene til rensning av den erholdte frie base, idet man overfører den frie base til salter, skiller disse fra og deretter frigir basen for saltene. På grunn av det nære forhold mellom den nye forbindelse i fri form og i form av sine salter skal i det fore-gående og det etterfølgende med fri base hensiktsmessig også eventuelt forstås de tilsvarende salter. These or other salts of the new compound such as e.g. picrates, can also serve to purify the free base obtained, as one transfers the free base to salts, separates these from and then releases the base from the salts. Due to the close relationship between the new compound in free form and in the form of its salts, in the foregoing and the following, free base should appropriately also be understood as the corresponding salts.
Den nye forbindelse kan foreligge som racemat eller i form av antipodene. Racemat kan på vanlig måte deles opp i antipodene. The new compound can exist as a racemate or in the form of the antipodes. Racemat can be divided into the antipodes in the usual way.
Utgangsstoffene er kjente og kan fremstilles etter i og for seg kjente metoder. The starting materials are known and can be prepared according to methods known per se.
2-oksoforbindelsen får man f. eks. ved at man omsetter forbindelser med formelen The 2-oxo compound is obtained, e.g. by reacting compounds with the formula
med hverandre, hvori en av restene X og Y, er en reaksjonsdyktig forestret hydroksylgruppe, som en av de ovenfor nevnte, og den andre er den frie aminogruppe. Reaksjonen gjennomføres fortrinnsvis i nærvær av et basisk kondensasjonsmiddel. with each other, in which one of the residues X and Y is a reactive esterified hydroxyl group, such as one of those mentioned above, and the other is the free amino group. The reaction is preferably carried out in the presence of a basic condensing agent.
Forbindelser som ved nitrogenatomet og/eller ved 2-hydroksylgruppen har en ved hydrolyse eller hydrogenolyse avspaltbar rest, får man f. eks. ved kondensasjon av o-allyloksy-fenol eller et salt herav med en 3-isopropylamino-l,2-epoksypropan, som ved nitrogenatomet har en avspaltbar rest eller med en 3-isopropylamino-2-hydroksy-l-X-propan, hvori X er en reaksjonsdyktig forestret hydroksylgruppe og som ved nitrogenatomet og/eller ved 2-hydroksylgruppen har en avspaltbar rest. Compounds which, at the nitrogen atom and/or at the 2-hydroxyl group, have a residue that can be split off by hydrolysis or hydrogenolysis, you get e.g. by condensation of o-allyloxy-phenol or a salt thereof with a 3-isopropylamino-1,2-epoxypropane, which has a cleavable residue at the nitrogen atom or with a 3-isopropylamino-2-hydroxy-1-X-propane, where X is a reactive esterified hydroxyl group and which has a cleavable residue at the nitrogen atom and/or at the 2-hydroxyl group.
Oppfinnelsen beskrives nærmere i de følg-ende eksempler. Temperaturen er angitt i Cel-siusgrader. The invention is described in more detail in the following examples. The temperature is indicated in degrees Celsius.
Eksempel 1:Example 1:
En oppløsning av 15 g 3-(o-allyloksy-fenoksy) -1,2-epoksy-propan og 15 g ispropylamin i 20 ml etanol kokes i fire timer med tilbakeløpskjø-ler. Overskudd av amin og alkohol avdestilleres i vakuum. Det blir tilbake l-isopropylamin-2-hydroksy-3-(o-allyloksy-fenoksy)-propan med formelen A solution of 15 g of 3-(o-allyloxy-phenoxy)-1,2-epoxy-propane and 15 g of isopropylamine in 20 ml of ethanol is boiled for four hours with reflux condensers. Excess amine and alcohol are distilled off in vacuum. This leaves 1-isopropylamine-2-hydroxy-3-(o-allyloxy-phenoxy)-propane with the formula
som etter omkrystallisasjon fra heksan smelter ved 75—80° C. which after recrystallization from hexane melts at 75-80° C.
Utgangsproduktet fremstilles som følger:The starting product is produced as follows:
75 g pyrokatekin-monoallyleter, 75 g eplklor-hydrin, 75 g pottaske og 400 ml aceton oppvarmes under omrøring i 12 timer til kokning. Pott-asken frafiltreres deretter. Oppløsningsmidlet destilleres i vannstrålevakuum. Det blir tilbake en olje som oppløses i eter og rystes ut med 2-n natronlut. Eteren skylles fra, tørkes og avdestilleres. Den tilbakeværende rest destilleres i vannstrålevakuum. 3-(o-allyloksy-fenoksy)-1,2-epok-sy-propan destillerer ved Kpn145—157°. 75 g pyrocatechin monoallyl ether, 75 g apple chlorohydrin, 75 g pot ash and 400 ml acetone are heated with stirring for 12 hours until boiling. The pot ash is then filtered off. The solvent is distilled in a water jet vacuum. An oil remains, which is dissolved in ether and shaken out with 2-n caustic soda. The ether is rinsed off, dried and distilled off. The remaining residue is distilled in a water jet vacuum. 3-(o-allyloxy-phenoxy)-1,2-epoxy-propane distils at Kpn 145-157°.
Eksempel 2:Example 2:
En oppløsning av 12,0 g 1-(o-allyloksy-fenoksy)-3-klor-isopropanol i 50 ml alkohol til-settes langsomt 9,0 g isopropylamin og deretter oppvarmes i 5 timer til 70° C. Reaksjonsblandin-gen inndampes i vakuum. Resten oppløses i 2-n A solution of 12.0 g of 1-(o-allyloxy-phenoxy)-3-chloro-isopropanol in 50 ml of alcohol is slowly added to 9.0 g of isopropylamine and then heated for 5 hours to 70° C. The reaction mixture is evaporated in vacuum. The remainder is dissolved in 2-n
saltsyre og ekstraheres med eter. Det vandige lag skilles fra, innstilles alkalisk med natronlut og ekstraheres med eter. Etter tørkning og inndampning av oppløsningsmidlet blir det tilbake en olje som krystalliserer langsomt. Ved omkrystallisasjon fra heksan fåes 1-isopropylamino-2-hydroksy-3-(o-allyloksy-fenoksy)-propan med formelen hydrochloric acid and extracted with ether. The aqueous layer is separated, made alkaline with caustic soda and extracted with ether. After drying and evaporation of the solvent, an oil remains which crystallizes slowly. By recrystallization from hexane, 1-isopropylamino-2-hydroxy-3-(o-allyloxy-phenoxy)-propane is obtained with the formula
som smelter ved 78—80° C. Hydrokloridet smelter ved 107—109° C. which melts at 78-80° C. The hydrochloride melts at 107-109° C.
Det som utgangsmateriale anvendte l-(p-allyloksyfenoksy)-3-klor-isopropanol fåes ved omsetning av 3-(o-allyloksy-fenoksy)-1,2-epok-sypropan med saltsyre. Forbindelsen koker ved 115—125° C/0,2 mm. The 1-(p-allyloxyphenoxy)-3-chloroisopropanol used as starting material is obtained by reacting 3-(o-allyloxyphenoxy)-1,2-epoxypropane with hydrochloric acid. The compound boils at 115-125° C/0.2 mm.
Eksempel 3:Example 3:
En oppløsning av 15,0 g l-amino-2-hydroksy-3-(o-allyloksy-fenoksy)-propan og 8,0 g iso-propylbromid i 150 ml alkohol oppvarmes etter tilsetning av 5,0 g pottaske i 4 timer til kokning. Hertil filtreres uoppløst mengde. Filtratet inndampes. Residuet forsåpes med 100 ml 2-n saltsyre og ekstraheres med eter. Det vandige sjikt gjør man alkalisk med 10-n natronlut og ekstraherer den utskilte base med eter. Det etter tørkning og oppløsningsmidlets inndampning gjenblivende residuum omkrystalliseres flere ganger fra heksan. Man får l-isopropylamino-2-hydroksy-3-(o-allyloksyfenoksy)-propan med formelen A solution of 15.0 g of 1-amino-2-hydroxy-3-(o-allyloxy-phenoxy)-propane and 8.0 g of iso-propyl bromide in 150 ml of alcohol is heated after the addition of 5.0 g of pot ash for 4 hours for cooking. In addition, the undissolved amount is filtered. The filtrate is evaporated. The residue is saponified with 100 ml of 2-n hydrochloric acid and extracted with ether. The aqueous layer is made alkaline with 10-n caustic soda and the separated base is extracted with ether. The residue remaining after drying and evaporation of the solvent is recrystallized several times from hexane. 1-isopropylamino-2-hydroxy-3-(o-allyloxyphenoxy)-propane is obtained with the formula
i krystaller av sm.p. 74—78° C, hydrokloridets sm.p. 107—109° C. in crystals of m.p. 74-78° C, the m.p. of the hydrochloride. 107-109°C.
Det som utgangsmateriale anvendte 1-amino-2-hydroksy-3- (o-allyloksy-fenoksy) - propan lar seg fremstille på følgende måte: En blanding av 200 g o-benzyloksy-fenol, 200 g epiklorhydrin, 200 g pottaske og 800 ml aceton oppvarmes i 12 timer under omrøring til kokning. Den uoppløste del frafiltreres og til filtratet setter man 1 000 ml eter. For å fjerne fenoliske deler utrystes med natronlut. Eteropp- løsningen tørkes over natriumsulfat og inndampes deretter i vannstrålevakuum. Residuet destillerer man i høyvakuum. Man får 3-(o-benzyloksy-l,2-epoksy-propan som olje, som koker ved 142—153° C ved 0,1 mm Hg. 30 g 3-(o-benzyloksy-fenoksy)-l,2-epoksy-propan oppvarmes med 30 g benzylamin i 30 ml etanol i 4 timer til kokning. Deretter inndamper man i vannstrålevakuum, oppløser residuet i 200 ml 2-n saltsyre og ekstraherer med eter. Den sure oppløsning gjøres alkalisk med 10-n natronlut. Man ekstraherer den utskilte base med eter, tørker ekstraktet over natriumsulfat og avdestil-lerer oppløsningsmidlet. Det ble tilbake 1-ben-zylamino-2-hydroksy-3- (o-benzyloksy-fenoksy) - propan, som smelter etter omkrystallisering fra isopropanol ved 82—83° C. 25 g l-benzylamino-2-hydroksy-3-(o-benzyl-oksyfenoksy)-propan oppløses i 250 ml etanol og hydreres etter tilsetning av 3,0 g palladiumkull ved værelsetemperatur og normaltrykk. Etter avslutning av hydrogenopptaket frafiltrerer man katalysatoren og inndamper i vakuum. Man får 1- amino-2-hydroksy-3-(o-hydroksy-fenoksy)-propan, hvis hydroklorid smelter ved 175—177° C. The 1-amino-2-hydroxy-3-(o-allyloxy-phenoxy)-propane used as starting material can be prepared in the following way: A mixture of 200 g of o-benzyloxy-phenol, 200 g of epichlorohydrin, 200 g of pot ash and 800 ml of acetone is heated for 12 hours with stirring until boiling. The undissolved part is filtered off and 1,000 ml of ether is added to the filtrate. To remove phenolic parts, shake with caustic soda. The ether solution is dried over sodium sulphate and then evaporated in a water jet vacuum. The residue is distilled under high vacuum. 3-(o-benzyloxy-1,2-epoxy-propane is obtained as an oil, which boils at 142-153° C at 0.1 mm Hg. 30 g of 3-(o-benzyloxy-phenoxy)-1,2- epoxy-propane is heated with 30 g of benzylamine in 30 ml of ethanol for 4 hours until boiling. Then, one evaporates in a water jet vacuum, dissolves the residue in 200 ml of 2-N hydrochloric acid and extracts with ether. The acidic solution is made alkaline with 10-N sodium hydroxide solution. Man extracting the separated base with ether, drying the extract over sodium sulfate and distilling off the solvent, 1-benzylamino-2-hydroxy-3-(o-benzyloxy-phenoxy)-propane remained, which melts after recrystallization from isopropanol at 82 -83° C. 25 g of 1-benzylamino-2-hydroxy-3-(o-benzyl-oxyphenoxy)-propane are dissolved in 250 ml of ethanol and hydrated after the addition of 3.0 g of palladium charcoal at room temperature and normal pressure. After completion of the hydrogen absorption the catalyst is filtered off and evaporated in vacuo.1-amino-2-hydroxy-3-(o-hydroxy-phenoxy)-propane is obtained, the hydrochloride of which melts at 175-177° C .
Til en oppløsning av 5,4 g natriummetylat i 200 ml etanol setter man 22 g l-amino-2-hydroksy-3-(o-hydroksy-fenoksy)-propan og lar det langsomt tildryppe 12,0 g allylbromid. Man omrører i 4 timer ved værelsetemperatur og frafiltrerer deretter. Filtratet inndamper man i vakuum. Man får l-amino-2-hydroksy-3-(o-allyloksyfenoksy)-propan som olje, som direkte videre forarbeides. To a solution of 5.4 g of sodium methylate in 200 ml of ethanol, 22 g of 1-amino-2-hydroxy-3-(o-hydroxy-phenoxy)-propane are added and 12.0 g of allyl bromide is allowed to slowly drip into it. It is stirred for 4 hours at room temperature and then filtered off. The filtrate is evaporated in a vacuum. 1-Amino-2-hydroxy-3-(o-allyloxyphenoxy)-propane is obtained as an oil, which is directly further processed.
Eksempel 4:Example 4:
20 g o-allyloksy-fenol, 15 g 3-isopropylamino-2- hydroksy-l-klorpropan og 20 g finmalt pottaske omrøres i 300 ml aceton i 5 timer ved 50° C. Den uoppløste del frafiltrerer man og inndamper acetonoppløsningen i vannstrålevakuum. Residuet oppløses i eter og ekstraheres med 2-n natronlut. Etersjiktet fraskiller man og inndamper til tørrhet. Det blir tilbake l-isopropylamino-2-hydroksy-3- (o-allyloksy-fenoksy) -propan med formelen 20 g of o-allyloxy-phenol, 15 g of 3-isopropylamino-2-hydroxy-l-chloropropane and 20 g of finely ground pot ash are stirred in 300 ml of acetone for 5 hours at 50° C. The undissolved part is filtered off and the acetone solution is evaporated in a water jet vacuum. The residue is dissolved in ether and extracted with 2-n caustic soda. The ether layer is separated and evaporated to dryness. This leaves 1-isopropylamino-2-hydroxy-3-(o-allyloxy-phenoxy)-propane with the formula
som etter sublimering smelter ved 78—81° C. Hydrokloridet smelter ved 107—109° C. which after sublimation melts at 78-81° C. The hydrochloride melts at 107-109° C.
Eksempel 5:Example 5:
1 g l-(N-acetyl-isopropylamino)-2-acetoksy-3-(o-allyloksy-fenoksy)-propan kokes i 7 ml ab-solutt alkohol og 3,5 ml 5-n natronlut i 7 timer under tilbakeløp. Reaksjonsoppløsnihgen inndampes i vakuum. Inndampningsresiduet blan-der man med vann og utryster med eter. Etter inndampning av den tørkede eteroppløsning får man som residum l-isopropylamino-2-hydroksy-3-(o-allyloksy-fenoksy)-propan med formelen 1 g of 1-(N-acetyl-isopropylamino)-2-acetoxy-3-(o-allyloxy-phenoxy)-propane is boiled in 7 ml of absolute alcohol and 3.5 ml of 5-n caustic soda for 7 hours under reflux. The reaction solution is evaporated in vacuo. The evaporation residue is mixed with water and shaken with ether. After evaporation of the dried ether solution gives as a residue 1-isopropylamino-2-hydroxy-3-(o-allyloxy-phenoxy)-propane with the formula
Eksempel 6: Example 6:
10,0 g 3-isopropyl-5-(o-allyloksy-fenoksy-metyl)-oksazolidon-(2) oppvarmes med 50 ml 10-n natronlut i 15 min. under god omrøring ved 120° C. Hertil setter man 200 ml vann og ekstra- ' herer med eter. Etersjiktet adskilles, tørkes og inndampes i vannstrålevakuum. Det gjenblir 1-isopropylamino-2-hydroksy-3-(o-allyloksy-fenoksy)-propan med formelen 10.0 g of 3-isopropyl-5-(o-allyloxy-phenoxy-methyl)-oxazolidone-(2) is heated with 50 ml of 10-n caustic soda for 15 min. with good stirring at 120° C. Add 200 ml of water to this and extract with ether. The ether layer is separated, dried and evaporated in a water jet vacuum. This leaves 1-isopropylamino-2-hydroxy-3-(o-allyloxy-phenoxy)-propane with the formula
som etter omkrystallisering fra heksan smelter ved 78—81° C. Hydrokloridet smelter ved 107— 109° C. which after recrystallization from hexane melts at 78-81° C. The hydrochloride melts at 107-109° C.
Eksempel 7:Example 7:
En oppløsning av 15,0 g l-amino-2-hydroksy-3-(o-allyloksy-fenoksy)-propan i 30 ml etanol og 30 ml aceton kokes i 5 timer under tilbakeløp. Derpå inndamper man i vannstrålevakuum. Residuet oppløses i 100 ml metanol og under om-røring setter man til oppløsningen 5,0 g natriumborhydrid. Ettr 4 timer setter man til reaksjons-blandingen 300 ml vann og 100 ml 2-n saltsyre. Den vandige oppløsning ekstraheres med eter og gjøres deretter alkalisk ved tilsetning av 10-n natronlut. Man ekstraherer to ganger med eter, tørker ekstraktet over natriumsulfat og inndamper i vakuum. Man får en olje som krystalliserer langsomt. Ved omkrystallisering fra petroleter fåes l-isopropylamino-2-hydroksy-3- (o-allyloksy)-propan med formelen A solution of 15.0 g of 1-amino-2-hydroxy-3-(o-allyloxy-phenoxy)-propane in 30 ml of ethanol and 30 ml of acetone is boiled for 5 hours under reflux. It is then evaporated in a water jet vacuum. The residue is dissolved in 100 ml of methanol and, with stirring, 5.0 g of sodium borohydride is added to the solution. After 4 hours, 300 ml of water and 100 ml of 2-N hydrochloric acid are added to the reaction mixture. The aqueous solution is extracted with ether and then made alkaline by the addition of 10-n caustic soda. Extract twice with ether, dry the extract over sodium sulphate and evaporate in vacuo. You get an oil that crystallizes slowly. On recrystallization from petroleum ether, l-isopropylamino-2-hydroxy-3-(o-allyloxy)-propane is obtained with the formula
med sm.p. 76—81° C. Hydrokloridets sm.p. 107— 109° C. with sm.p. 76—81° C. The hydrochloride's m.p. 107— 109° C.
Det som utgangsmateriale anvendte 1-amino-2-hydroksy-3- (o-allyloksy-fenoksy) -propan lar seg fremstille på følgende måte: En blanding av 200 g o-benzyloksy-fenol, 200 g pottaske og 800 ml aceton oppvarmes i 12 timer under omrøring til kokning. Den uoppløste del frafiltrerer man og setter til filtratet 1 000 ml The 1-amino-2-hydroxy-3-(o-allyloxy-phenoxy)-propane used as starting material can be prepared in the following way: A mixture of 200 g of o-benzyloxy-phenol, 200 g of pot ash and 800 ml of acetone is heated in 12 hours while stirring until boiling. The undissolved part is filtered off and 1,000 ml is added to the filtrate
eter. For å fjerne fenoliske deler utrystes med ether. To remove phenolic parts, equip with
natronlut. Eteroppløsningen tørkes over natriumsulfat og inndampes deretter i vannstrålevakuum. Residuet destillerer man i høyvakuum. baking soda. The ether solution is dried over sodium sulphate and then evaporated in a water jet vacuum. The residue is distilled under high vacuum.
Man får 3-(o-benzyloksy-f enoksy)-1-epoksy-propan som olje, som koker ved 142—153° C ved 3-(o-benzyloxy-phenoxy)-1-epoxy-propane is obtained as an oil, which boils at 142-153° C at
0,1 mm Hg.0.1 mm Hg.
30 g 3-(o-benzyloksy-fenoksy)-l,2-epoksy-propan oppvarmes med 30 g benzylamin i 30 ml 30 g of 3-(o-benzyloxy-phenoxy)-1,2-epoxy-propane are heated with 30 g of benzylamine in 30 ml
etanol i 4 timer til kokning. Deretter inndamper ethanol for 4 hours until boiling. Then evaporates
man i vannstrålevakuum, oppløser residuet i one in a water jet vacuum, dissolves the residue i
200 ml 2-n saltsyre og ekstraherer med eter. Hele 200 ml of 2-n hydrochloric acid and extract with ether. All
oppløsningen gjøres alkalisk med 10-n natronlut. Man ekstraherer den utskilte base med eter, the solution is made alkaline with 10-n caustic soda. The separated base is extracted with ether,
tørker ekstraktet over natriumsulfat og avdestil-lerer oppløsningsmidlet. Det blir tilbake 1-ben-zylamino-2-hydroksy-3-(o-benzyloksy-f enoksy)-propan, som etter omkrystallisering fra isopropanol smelter ved 82—83° C. dries the extract over sodium sulphate and distills off the solvent. What remains is 1-benzylamino-2-hydroxy-3-(o-benzyloxy-phenoxy)-propane, which after recrystallization from isopropanol melts at 82-83°C.
25 g l-benzylamino-2-hydroksy-3-(o-benzyl-oksyfenoksy)-propan oppløses i 250 ml etanol og 25 g of 1-benzylamino-2-hydroxy-3-(o-benzyl-oxyphenoxy)-propane are dissolved in 250 ml of ethanol and
hydreres etter tilsetning av 3,0 g palladiumkull is hydrated after adding 3.0 g of palladium charcoal
ved værelsetemperatur og normaltrykk. Etter at room temperature and normal pressure. After
hydrogenopptakets avslutning frafiltrerer man the end of the hydrogen uptake is filtered off
katalysatoren og inndamper i vakuum. Man får the catalyst and evaporate in a vacuum. You get
l-amino-2-hydroksy-3- (o-hydroksy-f enoksy) - 1-amino-2-hydroxy-3-(o-hydroxy-phenoxy)-
propan, hvis hydroklorid smelter ved 175°—177° propane, the hydrochloride of which melts at 175°—177°
C. C.
Til en oppløsning av 5,4 g natriummetylat i To a solution of 5.4 g of sodium methylate i
200 ml etanol setter man 22 g l-amino-2-hydroksy-3-(o-hydroksy-fenoksy)-propan og lar det 22 g of 1-amino-2-hydroxy-3-(o-hydroxy-phenoxy)-propane are added to 200 ml of ethanol and allowed to
langsomt tildryppe 12,0 g allylbromid. Man om-rører i 4 timer ved værelsetemperatur og frafiltrerer deretter. Filtratet damper man inn i vakuum. Man får l-amino-2-hydroksy-3-(o-allyloksy f enoksy)-propan som olje, som anvendes slowly add 12.0 g of allyl bromide dropwise. It is stirred for 4 hours at room temperature and then filtered off. The filtrate is evaporated in a vacuum. One obtains 1-amino-2-hydroxy-3-(o-allyloxyphenoxy)-propane as an oil, which is used
direkte til kondensasjon med aceton. directly to condensation with acetone.
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH1180164A CH451915A (en) | 1964-09-10 | 1964-09-10 | Process for the preparation of a new amine |
Publications (1)
Publication Number | Publication Date |
---|---|
NO115388B true NO115388B (en) | 1968-09-30 |
Family
ID=4376996
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO15964965A NO115388B (en) | 1964-09-10 | 1965-09-09 |
Country Status (14)
Country | Link |
---|---|
AT (4) | AT259544B (en) |
BE (1) | BE669402A (en) |
BR (1) | BR6573058D0 (en) |
CH (1) | CH451915A (en) |
CY (1) | CY445A (en) |
DE (1) | DE1242596B (en) |
DK (1) | DK117138B (en) |
FI (1) | FI45039C (en) |
FR (1) | FR4968M (en) |
GB (1) | GB1077603A (en) |
IL (1) | IL24187A (en) |
NL (2) | NL6511785A (en) |
NO (1) | NO115388B (en) |
SE (1) | SE322506B (en) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE457505B (en) * | 1984-01-10 | 1989-01-09 | Lejus Medical Ab | LAMINATED ORAL PHARMACEUTICAL COMPOSITION AND PROCEDURES FOR ITS PREPARATION |
SE8401907L (en) * | 1984-04-05 | 1985-10-06 | Haessle Ab | NEW PHENOXIPROPANOLAMINE SALTS AND PHARMACEUTICAL PREPARATIONS THEREOF |
SE453979B (en) * | 1986-07-04 | 1988-03-21 | Tetra Pak Ab | PACKAGING LAMINATE OF PAPER LAYER AND PLASTIC LAYER PROVIDED WITH AN ELECTRONIC RADIATION HARDENABLE FRESH LAYER, USE OF THE LAMINATE TO CONTAINER AND OF THE LAMINATE MANUFACTURED CONTAINER |
EA200500234A1 (en) | 2002-08-19 | 2005-08-25 | Пфайзер Продактс Инк. | COMBINED THERAPY OF HYPERPROLIFERATIVE DISEASES |
GT200600381A (en) | 2005-08-25 | 2007-03-28 | ORGANIC COMPOUNDS | |
US7741317B2 (en) | 2005-10-21 | 2010-06-22 | Bristol-Myers Squibb Company | LXR modulators |
US7888376B2 (en) | 2005-11-23 | 2011-02-15 | Bristol-Myers Squibb Company | Heterocyclic CETP inhibitors |
ES2382009T3 (en) | 2006-12-01 | 2012-06-04 | Bristol-Myers Squibb Company | N - ((3-Benzyl) -2,2- (bis-phenyl -) - propan-1-amine derivatives as CETP inhibitors for the treatment of atherosclerosis and cardiovascular diseases |
BR112015026513A2 (en) | 2013-04-17 | 2017-07-25 | Pfizer | n-piperidin-3-ylbenzamide derivatives to treat cardiovascular disease |
WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
MA54261A (en) | 2019-01-18 | 2022-04-27 | Astrazeneca Ab | PCSK9 INHIBITORS AND METHODS OF USE THEREOF |
-
0
- NL NL130749D patent/NL130749C/xx active
-
1964
- 1964-09-10 CH CH1180164A patent/CH451915A/en unknown
-
1965
- 1965-08-18 IL IL2418765A patent/IL24187A/en unknown
- 1965-08-19 DE DEC36681A patent/DE1242596B/en active Pending
- 1965-08-23 GB GB3604265A patent/GB1077603A/en not_active Expired
- 1965-09-06 DK DK456465A patent/DK117138B/en unknown
- 1965-09-09 AT AT825265A patent/AT259544B/en active
- 1965-09-09 FI FI216265A patent/FI45039C/en active
- 1965-09-09 AT AT1197066A patent/AT262978B/en active
- 1965-09-09 AT AT1196766A patent/AT262977B/en active
- 1965-09-09 AT AT1197966A patent/AT266081B/en active
- 1965-09-09 SE SE1177865A patent/SE322506B/xx unknown
- 1965-09-09 NO NO15964965A patent/NO115388B/no unknown
- 1965-09-09 NL NL6511785A patent/NL6511785A/xx unknown
- 1965-09-09 BE BE669402A patent/BE669402A/xx unknown
- 1965-09-10 BR BR17305865A patent/BR6573058D0/en unknown
- 1965-12-06 FR FR41000A patent/FR4968M/fr not_active Expired
-
1968
- 1968-07-15 CY CY44568A patent/CY445A/en unknown
Also Published As
Publication number | Publication date |
---|---|
AT262978B (en) | 1968-07-10 |
BE669402A (en) | 1966-03-09 |
FI45039C (en) | 1972-03-10 |
NL130749C (en) | |
DE1242596B (en) | 1967-06-22 |
AT259544B (en) | 1968-01-25 |
FR4968M (en) | 1967-04-03 |
SE322506B (en) | 1970-04-13 |
FI45039B (en) | 1971-11-30 |
DK117138B (en) | 1970-03-23 |
GB1077603A (en) | 1967-08-02 |
AT262977B (en) | 1968-07-10 |
CY445A (en) | 1968-07-15 |
NL6511785A (en) | 1966-03-11 |
AT266081B (en) | 1968-11-11 |
IL24187A (en) | 1969-04-30 |
CH451915A (en) | 1968-05-15 |
BR6573058D0 (en) | 1973-08-28 |
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