CH619219A5 - Process for the preparation of novel m-dioxane compounds - Google Patents
Process for the preparation of novel m-dioxane compounds Download PDFInfo
- Publication number
- CH619219A5 CH619219A5 CH1720873A CH1720873A CH619219A5 CH 619219 A5 CH619219 A5 CH 619219A5 CH 1720873 A CH1720873 A CH 1720873A CH 1720873 A CH1720873 A CH 1720873A CH 619219 A5 CH619219 A5 CH 619219A5
- Authority
- CH
- Switzerland
- Prior art keywords
- dioxane
- radical
- formula
- methylamine
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 39
- 230000008569 process Effects 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 12
- 150000000093 1,3-dioxanes Chemical class 0.000 title claims description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 75
- -1 methyl halide Chemical class 0.000 claims abstract description 45
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 16
- 230000002829 reductive effect Effects 0.000 claims abstract description 11
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 7
- 238000006264 debenzylation reaction Methods 0.000 claims abstract description 5
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- 239000002253 acid Substances 0.000 claims description 12
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 6
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical compound [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 230000000202 analgesic effect Effects 0.000 abstract description 23
- 150000003254 radicals Chemical class 0.000 abstract description 11
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 abstract description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 abstract description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 3
- 125000005059 halophenyl group Chemical group 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 2
- 239000001257 hydrogen Substances 0.000 abstract description 2
- 125000003944 tolyl group Chemical group 0.000 abstract description 2
- 230000001035 methylating effect Effects 0.000 abstract 1
- 208000024891 symptom Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 23
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 238000000921 elemental analysis Methods 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000000908 ammonium hydroxide Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000012259 ether extract Substances 0.000 description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 230000036407 pain Effects 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- AVOGLAYTIWJANJ-UHFFFAOYSA-N (5-methyl-1,3-dioxan-5-yl)-phenylmethanone Chemical compound C=1C=CC=CC=1C(=O)C1(C)COCOC1 AVOGLAYTIWJANJ-UHFFFAOYSA-N 0.000 description 4
- JCLLBAQTUYKIGM-UHFFFAOYSA-N 1,3-dioxan-5-ylmethanamine Chemical compound NCC1COCOC1 JCLLBAQTUYKIGM-UHFFFAOYSA-N 0.000 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000002262 Schiff base Substances 0.000 description 4
- 150000004753 Schiff bases Chemical class 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 230000036461 convulsion Effects 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229940050176 methyl chloride Drugs 0.000 description 4
- 150000002923 oximes Chemical class 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000011975 tartaric acid Substances 0.000 description 4
- 238000010998 test method Methods 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- CGDFUIJLIZDUCG-UHFFFAOYSA-N 1,3-dioxan-5-yl(phenyl)methanone Chemical class C=1C=CC=CC=1C(=O)C1COCOC1 CGDFUIJLIZDUCG-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 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 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 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
- 238000010438 heat treatment Methods 0.000 description 3
- 238000007069 methylation reaction Methods 0.000 description 3
- 229960005181 morphine Drugs 0.000 description 3
- MJIRSVYKUDHXGU-UHFFFAOYSA-N n-[(5-methyl-1,3-dioxan-5-yl)-phenylmethylidene]hydroxylamine Chemical compound C=1C=CC=CC=1C(=NO)C1(C)COCOC1 MJIRSVYKUDHXGU-UHFFFAOYSA-N 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical class C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 150000005840 aryl radicals Chemical class 0.000 description 2
- 239000003637 basic solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 125000006091 1,3-dioxolane group Chemical group 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 238000002574 cystoscopy Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- HGKAMARNFGKMLC-RBUKOAKNSA-N dexoxadrol Chemical compound C([C@H]1[C@@H]2OC(OC2)(C=2C=CC=CC=2)C=2C=CC=CC=2)CCCN1 HGKAMARNFGKMLC-RBUKOAKNSA-N 0.000 description 1
- 229950004665 dexoxadrol Drugs 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000026781 habituation Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- GPKUICFDWYEPTK-UHFFFAOYSA-N methoxycyclohexatriene Chemical compound COC1=CC=C=C[CH]1 GPKUICFDWYEPTK-UHFFFAOYSA-N 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- 150000003956 methylamines Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- KHUCQBZVGWVHNJ-UHFFFAOYSA-N n,n-dimethyl-1-(2-methyl-1,3-dioxolan-4-yl)methanamine Chemical compound CC1OCC(CN(C)C)O1 KHUCQBZVGWVHNJ-UHFFFAOYSA-N 0.000 description 1
- JHKXYYVISATNPA-UHFFFAOYSA-N n-[1,3-dioxan-5-yl(phenyl)methylidene]hydroxylamine Chemical compound C=1C=CC=CC=1C(=NO)C1COCOC1 JHKXYYVISATNPA-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical class CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 229910001120 nichrome Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- 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
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (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)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Pyridine Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31322172A | 1972-12-08 | 1972-12-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH619219A5 true CH619219A5 (en) | 1980-09-15 |
Family
ID=23214841
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1720873A CH619219A5 (en) | 1972-12-08 | 1973-12-07 | Process for the preparation of novel m-dioxane compounds |
| CH17977A CH614439A5 (en) | 1972-12-08 | 1973-12-07 | Process for the preparation of novel m-dioxane compounds |
| CH1720973A CH605903A5 (forum.php) | 1972-12-08 | 1973-12-07 | |
| CH805879A CH630914A5 (en) | 1972-12-08 | 1979-09-06 | Process for the preparation of new m-dioxane compounds |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH17977A CH614439A5 (en) | 1972-12-08 | 1973-12-07 | Process for the preparation of novel m-dioxane compounds |
| CH1720973A CH605903A5 (forum.php) | 1972-12-08 | 1973-12-07 | |
| CH805879A CH630914A5 (en) | 1972-12-08 | 1979-09-06 | Process for the preparation of new m-dioxane compounds |
Country Status (27)
| Country | Link |
|---|---|
| JP (2) | JPS5742633B2 (forum.php) |
| AR (3) | AR206306A1 (forum.php) |
| AT (2) | AT330773B (forum.php) |
| BE (1) | BE808340A (forum.php) |
| BG (4) | BG22386A3 (forum.php) |
| CA (2) | CA1014560A (forum.php) |
| CH (4) | CH619219A5 (forum.php) |
| CS (3) | CS222209B2 (forum.php) |
| CY (1) | CY1017A (forum.php) |
| DD (3) | DD109625A5 (forum.php) |
| DE (1) | DE2361340C2 (forum.php) |
| DK (1) | DK134717B (forum.php) |
| ES (4) | ES421291A1 (forum.php) |
| FR (1) | FR2209578B1 (forum.php) |
| GB (2) | GB1455997A (forum.php) |
| HK (1) | HK60479A (forum.php) |
| HU (2) | HU168620B (forum.php) |
| IE (1) | IE40226B1 (forum.php) |
| IL (1) | IL43773A (forum.php) |
| KE (1) | KE2976A (forum.php) |
| MY (1) | MY8000064A (forum.php) |
| NL (1) | NL7316839A (forum.php) |
| PH (2) | PH15197A (forum.php) |
| SE (3) | SE403377B (forum.php) |
| SU (4) | SU587861A3 (forum.php) |
| YU (3) | YU35447B (forum.php) |
| ZA (1) | ZA739207B (forum.php) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013169531A1 (en) * | 2012-05-09 | 2013-11-14 | Boehringer Ingelheim International Gmbh | Methods for making oxetan-3-ylmethanamines |
| LV14983B (lv) * | 2013-10-15 | 2015-06-20 | Olainfarm, A/S | Fenibuta ražošanas starpproduktu iegūšanas paņēmiens |
-
1973
- 1973-01-01 AR AR251422A patent/AR206306A1/es active
- 1973-12-04 ZA ZA00739207A patent/ZA739207B/xx unknown
- 1973-12-04 IE IE2190/73A patent/IE40226B1/xx unknown
- 1973-12-06 PH PH15299A patent/PH15197A/en unknown
- 1973-12-06 CA CA187,516A patent/CA1014560A/en not_active Expired
- 1973-12-07 NL NL7316839A patent/NL7316839A/xx not_active Application Discontinuation
- 1973-12-07 FR FR7343848A patent/FR2209578B1/fr not_active Expired
- 1973-12-07 YU YU3184/73A patent/YU35447B/xx unknown
- 1973-12-07 HU HUEI510A patent/HU168620B/hu unknown
- 1973-12-07 SU SU731977567A patent/SU587861A3/ru active
- 1973-12-07 AT AT1026073A patent/AT330773B/de not_active IP Right Cessation
- 1973-12-07 ES ES73421291A patent/ES421291A1/es not_active Expired
- 1973-12-07 BE BE1005568A patent/BE808340A/xx not_active IP Right Cessation
- 1973-12-07 ES ES73421290A patent/ES421290A1/es not_active Expired
- 1973-12-07 CH CH1720873A patent/CH619219A5/de not_active IP Right Cessation
- 1973-12-07 HU HUEI511A patent/HU168763B/hu unknown
- 1973-12-07 CA CA187,636A patent/CA1024150A/en not_active Expired
- 1973-12-07 AT AT1026173A patent/AT332396B/de not_active IP Right Cessation
- 1973-12-07 SU SU7301978316A patent/SU578001A3/ru active
- 1973-12-07 DK DK663373AA patent/DK134717B/da not_active IP Right Cessation
- 1973-12-07 IL IL43773A patent/IL43773A/xx unknown
- 1973-12-07 CH CH17977A patent/CH614439A5/xx not_active IP Right Cessation
- 1973-12-07 SE SE7316586A patent/SE403377B/xx unknown
- 1973-12-07 CH CH1720973A patent/CH605903A5/xx not_active IP Right Cessation
- 1973-12-07 AR AR251423A patent/AR212416A1/es active
- 1973-12-07 YU YU3185/73A patent/YU36171B/xx unknown
- 1973-12-08 BG BG027548A patent/BG22386A3/xx unknown
- 1973-12-08 BG BG028632A patent/BG26205A4/xx unknown
- 1973-12-08 DE DE2361340A patent/DE2361340C2/de not_active Expired
- 1973-12-08 BG BG025193A patent/BG21223A3/xx unknown
- 1973-12-08 BG BG028633A patent/BG21409A3/xx unknown
- 1973-12-08 JP JP48140246A patent/JPS5742633B2/ja not_active Expired
- 1973-12-08 JP JP14024573A patent/JPS5734835B2/ja not_active Expired
- 1973-12-10 CY CY1017A patent/CY1017A/xx unknown
- 1973-12-10 DD DD175231A patent/DD109625A5/xx unknown
- 1973-12-10 DD DD179119*A patent/DD115653A5/xx unknown
- 1973-12-10 GB GB5711373A patent/GB1455997A/en not_active Expired
- 1973-12-10 CS CS765892A patent/CS222209B2/cs unknown
- 1973-12-10 CS CS738529A patent/CS222208B2/cs unknown
- 1973-12-10 CS CS738528A patent/CS193480B2/cs unknown
- 1973-12-10 GB GB2900376A patent/GB1455998A/en not_active Expired
- 1973-12-10 DD DD175232A patent/DD110864A5/xx unknown
-
1975
- 1975-01-27 SU SU752100370A patent/SU648081A3/ru active
- 1975-02-19 SU SU752106121A patent/SU663305A3/ru active
- 1975-05-14 AR AR258799A patent/AR212012A1/es active
-
1976
- 1976-01-28 ES ES444716A patent/ES444716A1/es not_active Expired
- 1976-02-04 ES ES444911A patent/ES444911A1/es not_active Expired
- 1976-04-30 PH PH18384A patent/PH14923A/en unknown
-
1977
- 1977-02-17 SE SE7701796A patent/SE428378B/xx unknown
- 1977-02-17 SE SE7701795A patent/SE417196B/xx unknown
-
1979
- 1979-07-03 KE KE2976A patent/KE2976A/xx unknown
- 1979-08-23 HK HK604/79A patent/HK60479A/xx unknown
- 1979-09-06 CH CH805879A patent/CH630914A5/de not_active IP Right Cessation
-
1980
- 1980-04-22 YU YU1093/80A patent/YU36020B/xx unknown
- 1980-12-30 MY MY64/80A patent/MY8000064A/xx unknown
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| Date | Code | Title | Description |
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| PL | Patent ceased | ||
| PL | Patent ceased |