HU177640B - Process for preparing new laevorotatory derivatives of 3-phenoxy-morphinene - Google Patents
Process for preparing new laevorotatory derivatives of 3-phenoxy-morphinene Download PDFInfo
- Publication number
- HU177640B HU177640B HU77HO2029A HUHO002029A HU177640B HU 177640 B HU177640 B HU 177640B HU 77HO2029 A HU77HO2029 A HU 77HO2029A HU HO002029 A HUHO002029 A HU HO002029A HU 177640 B HU177640 B HU 177640B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- compound
- defined above
- preparation
- ether
- Prior art date
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- ZHGQVRRAUKAFGN-KSEOMHKRSA-N (1S,9R,10R)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,13-tetraene Chemical class O(C1=CC=CC=C1)C=1C=CC=2C[C@@H]3[C@@H]4CCC=C[C@@]4(C=2C=1)CCN3 ZHGQVRRAUKAFGN-KSEOMHKRSA-N 0.000 title 1
- 238000004519 manufacturing process Methods 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 11
- XNJVYGJIDQNXTL-KSEOMHKRSA-N (1R,9R,10R)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene Chemical class C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1)[H])C2=CC=C3OC1=CC=CC=C1 XNJVYGJIDQNXTL-KSEOMHKRSA-N 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 150000002367 halogens Chemical group 0.000 claims abstract description 10
- 230000000202 analgesic effect Effects 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 4
- 239000003887 narcotic antagonist Substances 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 163
- 150000001875 compounds Chemical class 0.000 claims description 115
- -1 alkane carboxylic acid Chemical class 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 20
- 206010029897 Obsessive thoughts Diseases 0.000 claims description 16
- PWLXGNOVURURNQ-MDNUFGMLSA-N (-)-3-phenoxy-n-methylmorphinan Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1C)[H])C2=CC=C3OC1=CC=CC=C1 PWLXGNOVURURNQ-MDNUFGMLSA-N 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 6
- 238000005661 deetherification reaction Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 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 description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 162
- 239000000243 solution Substances 0.000 description 111
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 71
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 54
- 239000011541 reaction mixture Substances 0.000 description 40
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- 239000002585 base Substances 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 239000000706 filtrate Substances 0.000 description 22
- 239000003826 tablet Substances 0.000 description 22
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- 229910000027 potassium carbonate Inorganic materials 0.000 description 17
- 229910052802 copper Inorganic materials 0.000 description 16
- 239000010949 copper Substances 0.000 description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- 235000011181 potassium carbonates Nutrition 0.000 description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 238000009835 boiling Methods 0.000 description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 12
- 239000002775 capsule Substances 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
- 239000000908 ammonium hydroxide Substances 0.000 description 10
- 239000007789 gas Substances 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000000538 analytical sample Substances 0.000 description 9
- 235000006408 oxalic acid Nutrition 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 239000012280 lithium aluminium hydride Substances 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 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 8
- 239000003960 organic solvent Substances 0.000 description 8
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 6
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 229920000881 Modified starch Polymers 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 229960001375 lactose Drugs 0.000 description 5
- 239000012429 reaction media Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 229960004126 codeine Drugs 0.000 description 4
- 229960001270 d- tartaric acid Drugs 0.000 description 4
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 229960005181 morphine Drugs 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- OKCBBODMVLQPKM-LIXABZRUSA-N (1R,9R,10R)-17-(cyclopropylmethyl)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene hydrochloride Chemical compound Cl.C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1CC1CC1)[H])C2=CC=C3OC1=CC=CC=C1 OKCBBODMVLQPKM-LIXABZRUSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 239000004368 Modified starch Substances 0.000 description 3
- IHBSVVZENGBQDY-BBWFWOEESA-N N-Methyl morphinan Chemical compound C1C2=CC=CC=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 IHBSVVZENGBQDY-BBWFWOEESA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 3
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 235000019426 modified starch Nutrition 0.000 description 3
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 150000003512 tertiary amines Chemical class 0.000 description 3
- UFGSDRKHGXKSFZ-DUBNFAFMSA-N (-)-3-phenoxy-n-[2-(2-furyl)ethyl]morphinan oxalate Chemical compound OC(=O)C(O)=O.N1([C@H]2[C@@H]3CCCC[C@@]3(C3=CC(OC=4C=CC=CC=4)=CC=C3C2)CC1)CCC1=CC=CO1 UFGSDRKHGXKSFZ-DUBNFAFMSA-N 0.000 description 2
- POLBUGDCWRJCEO-XOGZZPMPSA-N (-)-3-phenoxy-n-cyclobutylmethylmorphinan hydrochloride Chemical compound Cl.C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1CC1CCC1)[H])C2=CC=C3OC1=CC=CC=C1 POLBUGDCWRJCEO-XOGZZPMPSA-N 0.000 description 2
- LDACTFZEVWTVBX-JVFQMWRPSA-N (-)-3-phenoxymorphinan hydrochloride Chemical compound Cl.C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1)[H])C2=CC=C3OC1=CC=CC=C1 LDACTFZEVWTVBX-JVFQMWRPSA-N 0.000 description 2
- RVBHHCPQIXEYRA-CVXIRMMQSA-N 1-[(1R,9R,10R)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-17-yl]-2-phenylethanone Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1C(=O)CC=1C=CC=CC=1)[H])C2=CC=C3OC1=CC=CC=C1 RVBHHCPQIXEYRA-CVXIRMMQSA-N 0.000 description 2
- XYYFHBGOYHWPFV-UHFFFAOYSA-N 2-methyl-1-[(4-phenoxyphenyl)methyl]-3,4,5,6,7,8-hexahydro-1h-isoquinoline Chemical compound CN1CCC(CCCC2)=C2C1CC(C=C1)=CC=C1OC1=CC=CC=C1 XYYFHBGOYHWPFV-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- NMFJSADPLJZVNC-UHFFFAOYSA-N 4-[(2-methyl-3,4,5,6,7,8-hexahydro-1h-isoquinolin-1-yl)methyl]phenol Chemical compound CN1CCC(CCCC2)=C2C1CC1=CC=C(O)C=C1 NMFJSADPLJZVNC-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- KHIVJMCELJPZHP-VXQMPNGUSA-N cyclobutyl-[(1R,9R,10R)-4-phenoxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-17-yl]methanone Chemical compound C([C@@]1([C@@H]2CCCC[C@@]2(C2=C3)CCN1C(=O)C1CCC1)[H])C2=CC=C3OC1=CC=CC=C1 KHIVJMCELJPZHP-VXQMPNGUSA-N 0.000 description 2
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
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- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
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- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
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- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 1
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- 238000010438 heat treatment Methods 0.000 description 1
- PUYCICVJCRLABY-UHFFFAOYSA-N heptane;oxolane Chemical compound C1CCOC1.CCCCCCC PUYCICVJCRLABY-UHFFFAOYSA-N 0.000 description 1
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229960004715 morphine sulfate Drugs 0.000 description 1
- 229940068864 morphine sulfate 10 mg Drugs 0.000 description 1
- GRVOTVYEFDAHCL-RTSZDRIGSA-N morphine sulfate pentahydrate Chemical compound O.O.O.O.O.OS(O)(=O)=O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O GRVOTVYEFDAHCL-RTSZDRIGSA-N 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- RLXDCJUIXHSXQD-UHFFFAOYSA-N oxalic acid;hydrate Chemical compound O.OC(=O)C(O)=O.OC(=O)C(O)=O RLXDCJUIXHSXQD-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000003755 preservative agent Substances 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
- 230000035484 reaction time Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
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- FOMOAEUYWZDTNS-PMUMKWKESA-N tetrahydrodesoxycodeine Chemical compound C([C@H]12)CCC[C@@]11CCN(C)[C@@H]2CC2=CC=C(OC)C(O)=C21 FOMOAEUYWZDTNS-PMUMKWKESA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
-
- 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
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C07D221/28—Morphinans
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74802276A | 1976-12-06 | 1976-12-06 | |
| US05/811,233 US4113729A (en) | 1976-12-06 | 1977-06-29 | 3-Phenoxymorphinans and derivatives thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU177640B true HU177640B (en) | 1981-11-28 |
Family
ID=27114858
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU77HO2029A HU177640B (en) | 1976-12-06 | 1977-12-05 | Process for preparing new laevorotatory derivatives of 3-phenoxy-morphinene |
Country Status (22)
| Country | Link |
|---|---|
| JP (1) | JPS5392776A (enExample) |
| AR (1) | AR219510A1 (enExample) |
| AT (1) | AT364826B (enExample) |
| AU (1) | AU514827B2 (enExample) |
| CA (1) | CA1088935A (enExample) |
| DE (1) | DE2754062A1 (enExample) |
| DK (1) | DK540977A (enExample) |
| ES (3) | ES464751A1 (enExample) |
| FI (1) | FI773636A7 (enExample) |
| FR (1) | FR2372808A1 (enExample) |
| GB (1) | GB1589792A (enExample) |
| HU (1) | HU177640B (enExample) |
| IE (1) | IE46003B1 (enExample) |
| IL (1) | IL53532A (enExample) |
| IT (1) | IT1143727B (enExample) |
| LU (1) | LU78638A1 (enExample) |
| MC (1) | MC1172A1 (enExample) |
| NL (1) | NL7713432A (enExample) |
| NO (1) | NO774155L (enExample) |
| NZ (1) | NZ185860A (enExample) |
| PT (1) | PT67363B (enExample) |
| SE (1) | SE7713779L (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4247697A (en) * | 1979-09-10 | 1981-01-27 | Hoffmann-La Roche Inc. | 3-Phenoxy morphinans and their derivatives |
| TW264473B (enExample) * | 1993-01-06 | 1995-12-01 | Hoffmann La Roche |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH543514A (de) * | 1967-08-25 | 1973-10-31 | Hoffmann La Roche | Verfahren zur Herstellung von Morphinanderivaten |
| JPS493961B1 (enExample) * | 1969-06-24 | 1974-01-29 |
-
1977
- 1977-11-30 FI FI773636A patent/FI773636A7/fi not_active Application Discontinuation
- 1977-12-05 IE IE2468/77A patent/IE46003B1/en unknown
- 1977-12-05 SE SE7713779A patent/SE7713779L/xx not_active Application Discontinuation
- 1977-12-05 LU LU7778638A patent/LU78638A1/xx unknown
- 1977-12-05 HU HU77HO2029A patent/HU177640B/hu unknown
- 1977-12-05 ES ES464751A patent/ES464751A1/es not_active Expired
- 1977-12-05 NL NL7713432A patent/NL7713432A/xx not_active Application Discontinuation
- 1977-12-05 NO NO774155A patent/NO774155L/no unknown
- 1977-12-05 AT AT0869277A patent/AT364826B/de not_active IP Right Cessation
- 1977-12-05 DE DE19772754062 patent/DE2754062A1/de not_active Withdrawn
- 1977-12-05 CA CA292,433A patent/CA1088935A/en not_active Expired
- 1977-12-05 MC MC771272A patent/MC1172A1/fr unknown
- 1977-12-05 JP JP14520377A patent/JPS5392776A/ja active Pending
- 1977-12-05 PT PT67363A patent/PT67363B/pt unknown
- 1977-12-05 NZ NZ185860A patent/NZ185860A/xx unknown
- 1977-12-05 IL IL53532A patent/IL53532A/xx unknown
- 1977-12-05 GB GB50495/77A patent/GB1589792A/en not_active Expired
- 1977-12-05 DK DK540977A patent/DK540977A/da unknown
- 1977-12-06 FR FR7736745A patent/FR2372808A1/fr active Granted
- 1977-12-06 AU AU31264/77A patent/AU514827B2/en not_active Expired
- 1977-12-06 IT IT30510/77A patent/IT1143727B/it active
- 1977-12-06 AR AR270265A patent/AR219510A1/es active
-
1978
- 1978-08-16 ES ES472572A patent/ES472572A1/es not_active Expired
- 1978-08-16 ES ES472573A patent/ES472573A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| PT67363A (en) | 1978-01-01 |
| IL53532A0 (en) | 1978-03-10 |
| NZ185860A (en) | 1980-10-24 |
| AT364826B (de) | 1981-11-25 |
| PT67363B (en) | 1979-12-17 |
| GB1589792A (en) | 1981-05-20 |
| ATA869277A (de) | 1981-04-15 |
| IT1143727B (it) | 1986-10-22 |
| ES464751A1 (es) | 1978-12-16 |
| NO774155L (no) | 1978-06-07 |
| MC1172A1 (fr) | 1978-09-25 |
| FR2372808A1 (fr) | 1978-06-30 |
| AR219510A1 (es) | 1980-08-29 |
| DK540977A (da) | 1978-06-07 |
| ES472572A1 (es) | 1979-02-16 |
| FI773636A7 (fi) | 1978-06-07 |
| NL7713432A (nl) | 1978-06-08 |
| AU514827B2 (en) | 1981-02-26 |
| CA1088935A (en) | 1980-11-04 |
| FR2372808B1 (enExample) | 1981-07-10 |
| JPS5392776A (en) | 1978-08-15 |
| IL53532A (en) | 1981-09-13 |
| IE46003L (en) | 1978-06-06 |
| DE2754062A1 (de) | 1978-06-08 |
| LU78638A1 (enExample) | 1979-02-02 |
| SE7713779L (sv) | 1978-06-07 |
| AU3126477A (en) | 1979-06-14 |
| ES472573A1 (es) | 1979-02-16 |
| IE46003B1 (en) | 1983-01-26 |
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