RU2012115456A - СПОСОБ ПОЛУЧЕНИЯ МЕТИЛОВОГО ЭФИРА 3-[(4S)-8-БРОМ-1-МЕТИЛ-6-(2-ПИРИДИНИЛ)-4Н-ИМИДАЗО[1,2-а][1,4]БЕНЗОДИАЗЕПИН-4-ИЛ]ПРОПИОНОВОЙ КИСЛОТЫ ИЛИ ЕГО БЕНЗОЛСУЛЬФОНАТНОЙ СОЛИ И СОЕДИНЕНИЯ, ПРИМЕНЯЕМЫЕ В ЭТОМ СПОСОБЕ - Google Patents
СПОСОБ ПОЛУЧЕНИЯ МЕТИЛОВОГО ЭФИРА 3-[(4S)-8-БРОМ-1-МЕТИЛ-6-(2-ПИРИДИНИЛ)-4Н-ИМИДАЗО[1,2-а][1,4]БЕНЗОДИАЗЕПИН-4-ИЛ]ПРОПИОНОВОЙ КИСЛОТЫ ИЛИ ЕГО БЕНЗОЛСУЛЬФОНАТНОЙ СОЛИ И СОЕДИНЕНИЯ, ПРИМЕНЯЕМЫЕ В ЭТОМ СПОСОБЕ Download PDFInfo
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- RU2012115456A RU2012115456A RU2012115456/04A RU2012115456A RU2012115456A RU 2012115456 A RU2012115456 A RU 2012115456A RU 2012115456/04 A RU2012115456/04 A RU 2012115456/04A RU 2012115456 A RU2012115456 A RU 2012115456A RU 2012115456 A RU2012115456 A RU 2012115456A
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- bromo
- propionic acid
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- 150000001875 compounds Chemical class 0.000 title claims abstract 23
- 238000000034 method Methods 0.000 title claims abstract 20
- YOIMNRZPSLYTHB-INIZCTEOSA-N 3-[(4s)-8-bromo-1-methyl-6-pyridin-2-yl-4h-imidazo[1,2-a][1,4]benzodiazepin-4-yl]propanoic acid Chemical compound N([C@@H](CCC(O)=O)C1=NC=C(N1C1=CC=C(Br)C=C11)C)=C1C1=CC=CC=N1 YOIMNRZPSLYTHB-INIZCTEOSA-N 0.000 title claims abstract 3
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 title claims abstract 3
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 150000004702 methyl esters Chemical class 0.000 claims abstract 13
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims abstract 12
- 239000003960 organic solvent Substances 0.000 claims abstract 6
- 235000019260 propionic acid Nutrition 0.000 claims abstract 6
- 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 claims abstract 6
- 125000002252 acyl group Chemical group 0.000 claims abstract 4
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 claims abstract 4
- 150000002497 iodine compounds Chemical class 0.000 claims abstract 4
- 239000007800 oxidant agent Substances 0.000 claims abstract 4
- -1 2-pyridinyl Chemical group 0.000 claims abstract 3
- HZJQEUWLDHFEAO-PXAZEXFGSA-N BrC1=CC2=C(N=C([C@@H](N=C2C2=NC=CC=C2)CCC(=O)O)NC[C@@H](C)O)C=C1 Chemical compound BrC1=CC2=C(N=C([C@@H](N=C2C2=NC=CC=C2)CCC(=O)O)NC[C@@H](C)O)C=C1 HZJQEUWLDHFEAO-PXAZEXFGSA-N 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims abstract 3
- 229940092714 benzenesulfonic acid Drugs 0.000 claims abstract 2
- 239000007795 chemical reaction product Substances 0.000 claims abstract 2
- 238000002955 isolation Methods 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- HXKKHQJGJAFBHI-GSVOUGTGSA-N (2R)-1-aminopropan-2-ol Chemical compound C[C@@H](O)CN HXKKHQJGJAFBHI-GSVOUGTGSA-N 0.000 claims 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 2
- XNAPZINCYDNWSC-AWEZNQCLSA-N OC(=O)CC[C@@H]1N=C(c2ccccn2)c2cc(Br)ccc2NC1=O Chemical compound OC(=O)CC[C@@H]1N=C(c2ccccn2)c2cc(Br)ccc2NC1=O XNAPZINCYDNWSC-AWEZNQCLSA-N 0.000 claims 2
- 230000003993 interaction Effects 0.000 claims 2
- KHVZPFKJBLTYCC-UHFFFAOYSA-N (2-amino-5-bromophenyl)-pyridin-2-ylmethanone Chemical compound NC1=CC=C(Br)C=C1C(=O)C1=CC=CC=N1 KHVZPFKJBLTYCC-UHFFFAOYSA-N 0.000 claims 1
- HXKKHQJGJAFBHI-VKHMYHEASA-N (2s)-1-aminopropan-2-ol Chemical compound C[C@H](O)CN HXKKHQJGJAFBHI-VKHMYHEASA-N 0.000 claims 1
- OHYMUFVCRVPMEY-ZETCQYMHSA-N (2s)-5-methoxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid Chemical compound COC(=O)CC[C@@H](C(O)=O)NC(=O)OC(C)(C)C OHYMUFVCRVPMEY-ZETCQYMHSA-N 0.000 claims 1
- XTOQMDCHFVDCCL-UHFFFAOYSA-N 4-[chloro(morpholin-4-yl)phosphoryl]morpholine Chemical compound C1COCCN1P(=O)(Cl)N1CCOCC1 XTOQMDCHFVDCCL-UHFFFAOYSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims 1
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims 1
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims 1
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 239000011877 solvent mixture Substances 0.000 claims 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 abstract 2
- 239000002253 acid Substances 0.000 abstract 1
- CZXGXYBOQYQXQD-UHFFFAOYSA-N methyl benzenesulfonate Chemical compound COS(=O)(=O)C1=CC=CC=C1 CZXGXYBOQYQXQD-UHFFFAOYSA-N 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- OGGHIJLVRRWYEI-UHFFFAOYSA-O COC(CCC(C(Nc(c(C(c1ncccc1)=O)c1)ccc1Br)=O)[NH3+])=O Chemical compound COC(CCC(C(Nc(c(C(c1ncccc1)=O)c1)ccc1Br)=O)[NH3+])=O OGGHIJLVRRWYEI-UHFFFAOYSA-O 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D213/40—Acylated substituent nitrogen atom
-
- 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
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pyridine Compounds (AREA)
Abstract
1. Способ получения метилового эфира 3-[(4S)-8-бром-1-метил-6-(2-пиридинил)-4H-имидазо[1,2-а][1,4]бензодиазепин-4-ил]пропионовой кислоты формулы (F)который включает взаимодействие метилового эфира 3-[(S)-7-бром-2-((R и/или S)-2-гидроксипропиламино)-5-пиридин-2-ил-3H-бензо[е][1,4]диазепин-3-ил]пропионовой кислоты формулы (EM)с окислителем, который является соединением гипервалентного йода формулы (DM)в которой R1 представляет собой ацил, такой как 1,1,1-триацетокси-1,1-дигидро-1,2-бензойодоксол-3(1H)-он (периодинан Десс-Мартина).2. Способ по п.1, отличающийся тем, что соединение формулы (EM) является метиловым эфиром 3-[(S)-7-бром-2-((R)-2-гидроксипропиламино)-5-пиридин-2-ил-3H-бензо[е][1,4]диазепин-3-ил]пропионовой кислоты формулы (E)3. Способ получения бензолсульфоната метилового эфира 3-[(4S)-8-бром-1-метил-6-(2-пиридинил)-4H-имидазо[1,2-а][1,4]бензодиазепин-4-ил]пропионовой кислоты формулы (P), который включает(a) взаимодействие метилового эфира 3-[(S)-7-бром-2-((R или S)-2-гидроксипропиламино)-5-пиридин-2-ил-3H-бензо[е][1,4]диазепин-3-ил]пропионовой кислоты формулы (EM)с окислителем, который является соединением гипервалентного йода формулы (DM)в котором R1 представляет собой ацил, такой как 1,1,1-триацетокси-1,1-дигидро-1,2-бензойодоксол-3(1H)-он (периодинан Десс-Мартина), и(b) обработку продукта реакции, полученного на стадии (a), бензолсульфоновой кислотой в органическом растворителе или смеси органических растворителей с тем, чтобы получить соединение (P), или, как один из вариантов, (с) выделение соединения (P) способами, которые обычно применяются в синтетической органической химии.4. Способ по п.3, отличающийся тем, что соединение формулы (EM) является метиловым эфиром 3-[(S)-7-бром-2-((R)-2-гидроксипропиламино)
Claims (13)
1. Способ получения метилового эфира 3-[(4S)-8-бром-1-метил-6-(2-пиридинил)-4H-имидазо[1,2-а][1,4]бензодиазепин-4-ил]пропионовой кислоты формулы (F)
который включает взаимодействие метилового эфира 3-[(S)-7-бром-2-((R и/или S)-2-гидроксипропиламино)-5-пиридин-2-ил-3H-бензо[е][1,4]диазепин-3-ил]пропионовой кислоты формулы (EM)
с окислителем, который является соединением гипервалентного йода формулы (DM)
в которой R1 представляет собой ацил, такой как 1,1,1-триацетокси-1,1-дигидро-1,2-бензойодоксол-3(1H)-он (периодинан Десс-Мартина).
3. Способ получения бензолсульфоната метилового эфира 3-[(4S)-8-бром-1-метил-6-(2-пиридинил)-4H-имидазо[1,2-а][1,4]бензодиазепин-4-ил]пропионовой кислоты формулы (P), который включает
(a) взаимодействие метилового эфира 3-[(S)-7-бром-2-((R или S)-2-гидроксипропиламино)-5-пиридин-2-ил-3H-бензо[е][1,4]диазепин-3-ил]пропионовой кислоты формулы (EM)
с окислителем, который является соединением гипервалентного йода формулы (DM)
в котором R1 представляет собой ацил, такой как 1,1,1-триацетокси-1,1-дигидро-1,2-бензойодоксол-3(1H)-он (периодинан Десс-Мартина), и
(b) обработку продукта реакции, полученного на стадии (a), бензолсульфоновой кислотой в органическом растворителе или смеси органических растворителей с тем, чтобы получить соединение (P), или, как один из вариантов, (с) выделение соединения (P) способами, которые обычно применяются в синтетической органической химии.
5. Способ по любому из предшествующих пунктов, отличающийся тем, что дополнительно включает получение метилового эфира 3-[(S)-7-бром-2-((R и/или S)-2-гидроксипропиламино)-5-пиридин-2-ил-3H-бензо[е][1,4]диазепин-3-ил]пропионовой кислоты формулы (EM) способом, включающим взаимодействие соединения формулы (E1)
с (R)-1-амино-2-пропанолом или (S)-1-амино-2-пропанолом.
6. Способ по п.5, отличающийся тем, что соединение формулы (E1) подвергают взаимодействию с (R)-1-амино-2-пропанолом.
7. Способ по п.5 или 6, отличающийся тем, что метиловый эфир 3-[(S)-7-бром-2-((R и/или S)-2-гидроксипропиламино)-5-пиридин-2-ил-3H-бензо[е][1,4]диазепин-3-ил]пропионовой кислоты формулы (EM) подвергают кристаллизации из растворителя или смеси растворителей, таких как этилацетат, изобутилацетат, 2-пропанол, толуол или этилацетат/гептан.
8. Способ по любому из предшествующих пунктов, отличающийся тем, что дополнительно включает получение соединения формулы (E1), как показано в п.10, способом, включающим взаимодействие метилового эфира 3-[(S)-7-бром-2-оксо-5-пиридин-2-ил-2,3-дигидро-1H-1,4-бензодиазепин-3-ил]пропионовой кислоты формулы (D)
с диизопропиламидом лития (LDA) и бис-морфолинофосфорилхлоридатом (BMPC).
9. Способ по любому из предшествующих пунктов, отличающийся тем, что дополнительно включает стадию получения метилового эфира 3-[(S)-7-бром-2-оксо-5-пиридин-2-ил-2,3-дигидро-1H-1,4-бензодиазепин-3-ил]пропионовой кислоты формулы (D) способом, включающим циклизацию соединения формулы (C)
путем обработки основанием в органическом растворителе или смеси органических растворителей.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP09011914.0 | 2009-09-18 | ||
EP09011914A EP2305647A1 (en) | 2009-09-18 | 2009-09-18 | Process for preparing 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4 H-imidazo[1,2-a][1,4]benzodiazepine-4-yl] propionic acid methyl ester or the benzene sulfonate salt thereof, and compounds useful in that process |
PCT/EP2010/005668 WO2011032692A1 (en) | 2009-09-18 | 2010-09-15 | Process for preparing 3-[(4s)-8-bromo-1-methyl-6-(2-pyridinyl)-4h-imidazol[1,2-a][1,4]benzodiazepine-4-yl]propionic acid methyl ester or the benzene sulfonate salt thereof, and compounds useful in that process |
Publications (2)
Publication Number | Publication Date |
---|---|
RU2012115456A true RU2012115456A (ru) | 2013-11-10 |
RU2551848C2 RU2551848C2 (ru) | 2015-05-27 |
Family
ID=41467237
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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RU2012115456/04A RU2551848C2 (ru) | 2009-09-18 | 2010-09-15 | Способ получения метилового эфира 3-[(4s)-8-бром-1-метил-6-(2-пиридинил)-4н-имидазо[1,2-а][1,4]бензодиазепин-4-ил]пропионовой кислоты или его бензолсульфонатной соли и соединения, применяемые в этом способе |
Country Status (18)
Country | Link |
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US (3) | US9156842B2 (ru) |
EP (2) | EP2305647A1 (ru) |
JP (1) | JP5801309B2 (ru) |
KR (1) | KR101801735B1 (ru) |
CN (1) | CN102753525B (ru) |
AU (1) | AU2010294873B2 (ru) |
BR (1) | BR112012006053B1 (ru) |
CA (1) | CA2774018C (ru) |
DK (1) | DK2477967T3 (ru) |
ES (1) | ES2555233T3 (ru) |
HK (1) | HK1173437A1 (ru) |
HR (1) | HRP20151316T1 (ru) |
HU (1) | HUE028298T2 (ru) |
MX (2) | MX337683B (ru) |
PL (1) | PL2477967T3 (ru) |
PT (1) | PT2477967E (ru) |
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EP2450039A1 (en) | 2010-11-08 | 2012-05-09 | PAION UK Ltd. | Dosing regimen for sedation with CNS 7056 (Remimazolam) |
CN102964349A (zh) * | 2011-08-31 | 2013-03-13 | 江苏恒瑞医药股份有限公司 | 苯并二氮杂*衍生物的托西酸盐及其多晶型、它们的制备方法和用途 |
SG11201501358SA (en) | 2012-08-31 | 2015-04-29 | Paion Uk Ltd | Method for administering hypnotic/sedative agent |
AR094963A1 (es) | 2013-03-04 | 2015-09-09 | Ono Pharmaceutical Co | Reacción de oxidación excelente en el índice de conversión |
CN103230595B (zh) * | 2013-05-05 | 2014-10-08 | 李友香 | 治疗精神疾病的组合物 |
CN103232454A (zh) * | 2013-05-05 | 2013-08-07 | 王元青 | 治疗精神疾病的药物 |
CN105726495B (zh) * | 2014-12-12 | 2019-03-29 | 宜昌人福药业有限责任公司 | 一种注射用短效苯并二氮杂卓盐药物组合物及其制备方法 |
CN106892924B (zh) * | 2015-12-17 | 2021-01-08 | 四川科伦博泰生物医药股份有限公司 | 短效苯并二氮*衍生物、其制备方法及其用途 |
CN107266452A (zh) * | 2016-04-08 | 2017-10-20 | 四川科伦药物研究院有限公司 | 苯并二氮杂*衍生物的盐及其晶体形式、制备方法和用途 |
CN109641000A (zh) | 2016-04-14 | 2019-04-16 | Paion英国有限公司 | 经口吸入和经鼻用的苯并二氮杂*类 |
CN108264499B (zh) * | 2017-01-04 | 2020-10-20 | 江苏恒瑞医药股份有限公司 | 一种苯并二氮杂*衍生物的制备方法 |
PT3580219T (pt) | 2017-02-09 | 2022-06-02 | Assia Chem Ind Ltd | Processo para a preparação de remimazolam e formas de estado sólido de sais de remimazolam |
ES2697918A1 (es) | 2017-07-28 | 2019-01-29 | Moehs Iberica Sl | Procedimiento para preparar ester metilico del acido 3-[(3s)-7-bromo-2-oxo-5-(piridin-2-il)-2,3-dihidro-1h-[1,4]-benzodiazepin-3-il] propionico, y compuestos utiles en ese procedimiento |
ES2709298B2 (es) | 2017-10-13 | 2019-08-21 | Moehs Iberica Sl | Procedimiento para preparar metil ester de acido 3-[(4s)-8-bromo-1-metil-6-(piridin-2-il)-4h-imidazo[1,2-a][1,4]benzodiazepin-4-il]-propionico, y compuestos utiles en ese procedimiento |
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ES2827125A1 (es) * | 2019-11-19 | 2021-05-19 | Moehs Iberica Sl | Intermedio util en la preparacion de remimazolam, su procedimiento de obtencion, y su uso en la obtencion de remimazolam |
KR102526590B1 (ko) * | 2020-06-19 | 2023-04-28 | 하나제약 주식회사 | 3-[(4S)-8-브로모-1-메틸-6-(2-피리디닐)-4H-이미다조[1,2-a][1,4]벤조디아제핀-4-일]프로피온산 메틸 에스테르의 제조방법 |
CN112358483A (zh) * | 2020-11-09 | 2021-02-12 | 中国药科大学 | 一类新型苯并二氮*类化合物、其制备方法及其用途 |
CN112321594B (zh) * | 2020-12-07 | 2022-05-20 | 扬子江药业集团有限公司 | 一种苯并二氮杂䓬类药物的制备方法 |
CN114644612B (zh) * | 2020-12-17 | 2023-04-28 | 成都苑东生物制药股份有限公司 | 一种苯二氮杂类神经抑制剂中间体化合物的制备方法 |
CN113717176B (zh) * | 2021-10-09 | 2022-07-05 | 上海再启生物技术有限公司 | 一种制备瑞马唑仑的方法 |
CN114014839A (zh) * | 2021-12-16 | 2022-02-08 | 上海再启生物技术有限公司 | 一种制备瑞马唑仑关键中间体的方法 |
WO2023194945A1 (en) | 2022-04-08 | 2023-10-12 | Fresenius Kabi Oncology Ltd. | An improved process for the preparation of remimazolam |
CN115385891A (zh) * | 2022-09-06 | 2022-11-25 | 上海药坦药物研究开发有限公司 | 一种瑞马唑仑中间体的制备方法 |
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JP2012505843A (ja) | 2008-10-16 | 2012-03-08 | パイオン ユーケー リミテッド | 術後疼痛管理のための極性オピオイドの投与スキーム |
JP4669584B2 (ja) | 2009-03-30 | 2011-04-13 | 日本製紙株式会社 | N−オキシル化合物の回収・再利用方法 |
EP2305647A1 (en) | 2009-09-18 | 2011-04-06 | PAION UK Limited | Process for preparing 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4 H-imidazo[1,2-a][1,4]benzodiazepine-4-yl] propionic acid methyl ester or the benzene sulfonate salt thereof, and compounds useful in that process |
JP5635275B2 (ja) | 2010-01-28 | 2014-12-03 | 日清紡ホールディングス株式会社 | アルコールの酸化方法 |
EP2450039A1 (en) | 2010-11-08 | 2012-05-09 | PAION UK Ltd. | Dosing regimen for sedation with CNS 7056 (Remimazolam) |
MA37581B1 (fr) | 2012-05-22 | 2016-07-29 | Paion Uk Ltd | Compositions comprenant des benzodiazépines à action rapide |
SG11201501358SA (en) | 2012-08-31 | 2015-04-29 | Paion Uk Ltd | Method for administering hypnotic/sedative agent |
AR094963A1 (es) | 2013-03-04 | 2015-09-09 | Ono Pharmaceutical Co | Reacción de oxidación excelente en el índice de conversión |
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HUE028298T2 (en) | 2016-12-28 |
HRP20151316T1 (hr) | 2016-01-15 |
KR20120102603A (ko) | 2012-09-18 |
AU2010294873A1 (en) | 2012-04-12 |
KR101801735B1 (ko) | 2017-11-27 |
US20120330007A1 (en) | 2012-12-27 |
CA2774018A1 (en) | 2011-03-24 |
US10000464B2 (en) | 2018-06-19 |
JP5801309B2 (ja) | 2015-10-28 |
AU2010294873B2 (en) | 2014-11-13 |
MX337683B (es) | 2016-03-15 |
WO2011032692A1 (en) | 2011-03-24 |
PL2477967T3 (pl) | 2016-04-29 |
BR112012006053B1 (pt) | 2021-11-16 |
CA2774018C (en) | 2018-01-30 |
CN102753525B (zh) | 2015-09-02 |
HK1173437A1 (zh) | 2013-05-16 |
US20170044135A1 (en) | 2017-02-16 |
JP2013505207A (ja) | 2013-02-14 |
PT2477967E (pt) | 2016-01-07 |
BR112012006053A2 (pt) | 2020-11-03 |
EP2477967B1 (en) | 2015-11-11 |
US20150368199A1 (en) | 2015-12-24 |
US9512078B2 (en) | 2016-12-06 |
DK2477967T3 (en) | 2015-12-21 |
EP2305647A1 (en) | 2011-04-06 |
RU2551848C2 (ru) | 2015-05-27 |
MX341093B (es) | 2016-08-08 |
US9156842B2 (en) | 2015-10-13 |
MX2012003183A (es) | 2012-05-08 |
ES2555233T3 (es) | 2015-12-29 |
EP2477967A1 (en) | 2012-07-25 |
CN102753525A (zh) | 2012-10-24 |
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