JP7181896B2 - オメカムティブメカルビルの合成 - Google Patents
オメカムティブメカルビルの合成 Download PDFInfo
- Publication number
- JP7181896B2 JP7181896B2 JP2019561794A JP2019561794A JP7181896B2 JP 7181896 B2 JP7181896 B2 JP 7181896B2 JP 2019561794 A JP2019561794 A JP 2019561794A JP 2019561794 A JP2019561794 A JP 2019561794A JP 7181896 B2 JP7181896 B2 JP 7181896B2
- Authority
- JP
- Japan
- Prior art keywords
- pmec
- solution
- pipn
- fnb
- piperazine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
Description
Claims (16)
- 工程(a)で生成された前記PMECを、メチレンクロリド、ジクロロエタン、2-メチルテトラヒドロフラン、又はこれらの混合物の溶液として単離する工程をさらに含む、請求項2に記載の方法。
- 前記単離する工程は、
(i)前記工程(a)で得られたPMECを有機溶媒で洗浄する工程;
(ii)塩基を加えてpHを8~14に変更することにより、塩基性水溶液を生成する工程;及び
(iii)メチレンクロリド、ジクロロエタン、2-メチルテトラヒドロフラン、又はこれらの混合物によって、前記工程(ii)の塩基性水溶液から前記PMECを抽出する工程
により行われる、請求項3に記載の方法。 - 工程(a)は水溶液中で行われる、請求項2に記載の方法。
- 工程(a)は、20~55℃の温度で1~12時間行われる、請求項2~5のいずれか一項に記載の方法。
- 前記FNBは、チオ硫酸ナトリウム水溶液及び塩化ナトリウム水溶液で洗浄される、請求項7に記載の方法。
- FNBはトルエンで抽出され、水酸化ナトリウム水溶液で洗浄される、請求項9に記載の方法。
- 前記PIPNは塩酸塩として生成される、請求項7~10のいずれか一項に記載の方法。
- 前記PMECリン酸塩水和物は、請求項2~6のいずれか一項に記載の方法によって調製される、請求項7~11のいずれか一項に記載の方法。
- 前記トリアルキルアミン塩基は、ジイソプロピルエチルアミン又はトリエチルアミンを含む、請求項7~12のいずれか一項に記載の方法。
- 前記FNB、前記トリアルキルアミン塩基、及び前記PMECリン酸塩水和物を混合する前に、ジエチルホスファイト及びトリアルキルアミンを加え、得られた混合物を30~65℃の温度で混合することをさらに含む、請求項7~13のいずれか一項に記載の方法。
- メチル4-(3-アミノ-2-フルオロベンジル)ピペラジン-1-カルボキシレート
(a)請求項7の方法によって調製されたメチル4-(2-フルオロ-3-ニトロベンジル)ピペラジン-1-カルボキシレート
(b)パラジウム触媒の存在下、トルエン及びアルコールの混合溶媒中で前記PIPN遊離塩基溶液を水素化して、粗PIPAを生成する工程であって、前記アルコールは、エタノール又はイソプロパノールを含む工程;並びに
(c)ヘプタン及びトルエン中で前記粗PIPAから前記PIPAを結晶化させる工程
を含む方法。 - 前記無機塩基は水酸化ナトリウムを含む、請求項15に記載の方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022130911A JP2022166243A (ja) | 2017-06-30 | 2022-08-19 | オメカムティブメカルビルの合成 |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762527174P | 2017-06-30 | 2017-06-30 | |
US62/527,174 | 2017-06-30 | ||
US201862664363P | 2018-04-30 | 2018-04-30 | |
US62/664,363 | 2018-04-30 | ||
PCT/US2018/040176 WO2019006231A1 (en) | 2017-06-30 | 2018-06-29 | SYNTHESIS OF OMECAMTIV MECARBIL |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP2022130911A Division JP2022166243A (ja) | 2017-06-30 | 2022-08-19 | オメカムティブメカルビルの合成 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2020526476A JP2020526476A (ja) | 2020-08-31 |
JP7181896B2 true JP7181896B2 (ja) | 2022-12-01 |
Family
ID=62976317
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
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JP2019561794A Active JP7181896B2 (ja) | 2017-06-30 | 2018-06-29 | オメカムティブメカルビルの合成 |
JP2022130911A Pending JP2022166243A (ja) | 2017-06-30 | 2022-08-19 | オメカムティブメカルビルの合成 |
Family Applications After (1)
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JP2022130911A Pending JP2022166243A (ja) | 2017-06-30 | 2022-08-19 | オメカムティブメカルビルの合成 |
Country Status (27)
Country | Link |
---|---|
US (3) | US11040956B2 (ja) |
EP (3) | EP4265597A3 (ja) |
JP (2) | JP7181896B2 (ja) |
KR (1) | KR102625774B1 (ja) |
CN (1) | CN110799503B (ja) |
AU (2) | AU2018294254C1 (ja) |
BR (1) | BR112019028205A2 (ja) |
CA (1) | CA3063102A1 (ja) |
CL (2) | CL2019003898A1 (ja) |
CY (1) | CY1124427T1 (ja) |
DK (1) | DK3645518T3 (ja) |
ES (1) | ES2882905T3 (ja) |
GE (1) | GEP20227340B (ja) |
HR (1) | HRP20211290T1 (ja) |
HU (1) | HUE055242T2 (ja) |
IL (2) | IL294834A (ja) |
LT (1) | LT3645518T (ja) |
MD (1) | MD3645518T2 (ja) |
MX (2) | MX2021013326A (ja) |
PL (1) | PL3645518T3 (ja) |
PT (1) | PT3645518T (ja) |
RS (1) | RS62328B1 (ja) |
SG (1) | SG10202111790YA (ja) |
SI (1) | SI3645518T1 (ja) |
TW (2) | TW202235415A (ja) |
UA (1) | UA127517C2 (ja) |
WO (1) | WO2019006231A1 (ja) |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2837038T3 (es) | 2013-03-14 | 2021-06-29 | Amgen Inc | Compuestos heterocíclicos y sus usos |
WO2019006235A1 (en) | 2017-06-30 | 2019-01-03 | Amgen Inc. | METHODS OF TREATING CARDIAC INSUFFICIENCY WITH CARDIAC SARCOMER ACTIVATORS |
PL3645518T3 (pl) | 2017-06-30 | 2021-12-06 | Amgen Inc. | Synteza omekamtywu mekarbilu |
MX2020002696A (es) | 2017-09-13 | 2020-09-25 | Amgen Inc | Compuestos de bisamida que activan el sarcomero y sus usos. |
EP3837009A1 (en) | 2018-08-17 | 2021-06-23 | Amgen, Inc | Salts and crystal forms of omecamtiv mecarbil |
WO2021070123A1 (en) * | 2019-10-09 | 2021-04-15 | Dr. Reddy’S Laboratories Limited | Solid forms of omecamtiv mecarbil dihydrochloride and processes thereof |
US20220411374A1 (en) * | 2019-10-09 | 2022-12-29 | Dr. Reddy's Laboratories Limited | Alternate processes for the preparation of omecamtiv mecarbil |
CA3212491A1 (en) | 2021-03-10 | 2022-09-15 | Sebastien Caille | Synthesis of omecamtiv mecarbil |
WO2023205291A2 (en) * | 2022-04-21 | 2023-10-26 | The Board Of Regents Of The University Of Oklahoma | Targeting myocardial tissue for delivery of therapeutic and imaging agents |
Citations (4)
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JP2009519939A (ja) | 2005-12-19 | 2009-05-21 | サイトキネティクス・インコーポレーテッド | 化合物、組成物および方法 |
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JP2016519071A (ja) | 2013-03-14 | 2016-06-30 | アムジエン・インコーポレーテツド | オメカムチブメカルビルの塩及び塩を調製するプロセス |
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US20070208000A1 (en) | 2005-12-15 | 2007-09-06 | Morgan Bradley P | Certain chemical entities, compositions and methods |
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WO2019006235A1 (en) | 2017-06-30 | 2019-01-03 | Amgen Inc. | METHODS OF TREATING CARDIAC INSUFFICIENCY WITH CARDIAC SARCOMER ACTIVATORS |
PL3645518T3 (pl) | 2017-06-30 | 2021-12-06 | Amgen Inc. | Synteza omekamtywu mekarbilu |
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EP3837009A1 (en) | 2018-08-17 | 2021-06-23 | Amgen, Inc | Salts and crystal forms of omecamtiv mecarbil |
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US20220411374A1 (en) | 2019-10-09 | 2022-12-29 | Dr. Reddy's Laboratories Limited | Alternate processes for the preparation of omecamtiv mecarbil |
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CA3200673A1 (en) | 2020-11-12 | 2022-05-19 | Amgen Inc. | Methods of treating heart failure by administering omecamtiv mecarbil |
CA3212491A1 (en) | 2021-03-10 | 2022-09-15 | Sebastien Caille | Synthesis of omecamtiv mecarbil |
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Patent Citations (4)
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JP2009519939A (ja) | 2005-12-19 | 2009-05-21 | サイトキネティクス・インコーポレーテッド | 化合物、組成物および方法 |
JP2010506896A (ja) | 2006-10-18 | 2010-03-04 | ファイザー・プロダクツ・インク | ビアリールエーテル尿素化合物 |
WO2010141817A1 (en) | 2009-06-05 | 2010-12-09 | Janssen Pharmaceutica Nv | Heteroaryl-substituted spirocyclic diamine urea modulators of fatty acid amide hydrolase |
JP2016519071A (ja) | 2013-03-14 | 2016-06-30 | アムジエン・インコーポレーテツド | オメカムチブメカルビルの塩及び塩を調製するプロセス |
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