CN114127069A - 苯酚衍生物的制造方法 - Google Patents
苯酚衍生物的制造方法 Download PDFInfo
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- CN114127069A CN114127069A CN202080051634.3A CN202080051634A CN114127069A CN 114127069 A CN114127069 A CN 114127069A CN 202080051634 A CN202080051634 A CN 202080051634A CN 114127069 A CN114127069 A CN 114127069A
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- 238000000034 method Methods 0.000 title claims abstract description 55
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- 230000008569 process Effects 0.000 title claims description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 148
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- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 54
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 54
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 52
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 28
- 125000003118 aryl group Chemical group 0.000 claims abstract description 28
- 229910052751 metal Inorganic materials 0.000 claims abstract description 13
- 239000002184 metal Substances 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims description 137
- 238000004519 manufacturing process Methods 0.000 claims description 125
- 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 92
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 72
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 52
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 125000002947 alkylene group Chemical group 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 29
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- 239000003960 organic solvent Substances 0.000 claims description 24
- 125000006239 protecting group Chemical group 0.000 claims description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
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- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 15
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 14
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- 238000005984 hydrogenation reaction Methods 0.000 claims description 10
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- CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 claims description 9
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 9
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- 229910052703 rhodium Inorganic materials 0.000 claims description 8
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- 150000003951 lactams Chemical group 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
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- 150000003335 secondary amines Chemical class 0.000 claims description 6
- 239000012448 Lithium borohydride Substances 0.000 claims description 5
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 5
- 229910000103 lithium hydride Inorganic materials 0.000 claims description 5
- 229910052987 metal hydride Inorganic materials 0.000 claims description 5
- 150000004681 metal hydrides Chemical class 0.000 claims description 5
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims description 5
- 229910000105 potassium hydride Inorganic materials 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 5
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- 239000012312 sodium hydride Substances 0.000 claims description 5
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- 239000005456 alcohol based solvent Substances 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
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- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 8
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical group N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims 2
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- 239000000243 solution Substances 0.000 description 67
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 34
- 239000007787 solid Substances 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- 238000004128 high performance liquid chromatography Methods 0.000 description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 28
- 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 27
- 229910052708 sodium Inorganic materials 0.000 description 27
- 239000011734 sodium Substances 0.000 description 27
- 239000000203 mixture Substances 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000001914 filtration Methods 0.000 description 24
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 23
- 239000012044 organic layer Substances 0.000 description 23
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 19
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- 238000006027 Birch reduction reaction Methods 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 239000007858 starting material Substances 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
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- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 14
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- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 14
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- 125000005843 halogen group Chemical group 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
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- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 10
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
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- ZCILODAAHLISPY-UHFFFAOYSA-N biphenyl ether Natural products C1=C(CC=C)C(O)=CC(OC=2C(=CC(CC=C)=CC=2)O)=C1 ZCILODAAHLISPY-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
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- 229910052801 chlorine Inorganic materials 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 229940125782 compound 2 Drugs 0.000 description 4
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
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- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
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- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
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- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005934 tert-pentyloxycarbonyl group Chemical group 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2019-134083 | 2019-07-19 | ||
| JP2019134083 | 2019-07-19 | ||
| PCT/JP2020/027769 WO2021015109A1 (ja) | 2019-07-19 | 2020-07-17 | フェノール誘導体の製造方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114127069A true CN114127069A (zh) | 2022-03-01 |
Family
ID=74193222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080051634.3A Pending CN114127069A (zh) | 2019-07-19 | 2020-07-17 | 苯酚衍生物的制造方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20220289748A1 (https=) |
| EP (1) | EP4001280A4 (https=) |
| JP (2) | JP7634480B2 (https=) |
| KR (1) | KR20220035378A (https=) |
| CN (1) | CN114127069A (https=) |
| AU (1) | AU2020317503A1 (https=) |
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| JP7816720B2 (ja) | 2021-11-25 | 2026-02-18 | エルジー エナジー ソリューション リミテッド | 負極活物質、負極、および二次電池 |
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| CZ281174B6 (cs) | 1993-08-13 | 1996-07-17 | Galena, A.S. | Způsob přípravy 3,14ß-dihydroxy-17-normorfinanu |
| JP6061857B2 (ja) * | 2011-09-09 | 2017-01-18 | 学校法人北里研究所 | モルヒナン誘導体 |
| AR091027A1 (es) | 2012-05-11 | 2014-12-30 | Purdue Pharma Lp | Analogos de benzomorfano y el usos de estos |
| WO2014021273A1 (ja) | 2012-07-30 | 2014-02-06 | 学校法人北里研究所 | モルヒナン誘導体 |
| JP2015180605A (ja) | 2012-07-30 | 2015-10-15 | 学校法人北里研究所 | モルヒナン誘導体 |
| US8946255B2 (en) | 2012-12-28 | 2015-02-03 | Purdue Pharma L.P. | Substituted morphinans and the use thereof |
| WO2014102587A1 (en) | 2012-12-28 | 2014-07-03 | Purdue Pharma L.P. | 7,8-cyclicmorphinan analogs |
| EP2966074B1 (en) | 2013-03-08 | 2018-07-25 | The Kitasato Institute | Morphinan derivative |
| EP3003311A2 (en) | 2013-05-24 | 2016-04-13 | Alkermes Pharma Ireland Limited | Methods for treating depressive symptoms |
| CN113292559B (zh) * | 2015-03-17 | 2024-04-02 | 日本化学药品株式会社 | 吗啡喃衍生物 |
| US10766864B2 (en) | 2015-05-08 | 2020-09-08 | Nektar Therapeutics | Morphinan derivatives for the treatment of neuropathic pain |
| AU2020317503A1 (en) * | 2019-07-19 | 2022-02-10 | Nippon Chemiphar Co., Ltd. | Method for producing phenol derivative |
| US12202830B2 (en) * | 2019-07-19 | 2025-01-21 | Nippon Chemiphar Co., Ltd. | Method for producing morphinan derivative |
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| JPWO2021015109A1 (https=) | 2021-01-28 |
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