JP6543330B2 - ベンゾジアゼピンの合成 - Google Patents
ベンゾジアゼピンの合成 Download PDFInfo
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- JP6543330B2 JP6543330B2 JP2017506266A JP2017506266A JP6543330B2 JP 6543330 B2 JP6543330 B2 JP 6543330B2 JP 2017506266 A JP2017506266 A JP 2017506266A JP 2017506266 A JP2017506266 A JP 2017506266A JP 6543330 B2 JP6543330 B2 JP 6543330B2
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- mixture
- diabetes
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- hydroxy
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- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/554—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
国際特許公開WO2011/137,135は、本化合物を調製するための一般的な方法を開示している。さらに、本化合物の詳細な合成は、実施例26に開示されている。J.Med.Chem、Vol 56、pp5094〜5114(2013年)はまた、本化合物を合成するための方法を開示している。
1)改善された合成において、合成ステップの数が減る。
2)改善された合成は、有意に、より費用効率が高い。
3)改善された合成は、いかなるクロマトグラフの精製も必要としない。
Bz ベンゾイル
TfOH トリフルオロメタンスルホン酸
PhCOCl 塩化ベンゾイル
Tf2O 無水トリフルオロ酢酸
Py ピリジン
DME ジメトキシエタン
MTBE メチルt-ブチルエーテル
EtOAc 酢酸エチル
HOAc 酢酸
EtOH エタノール
MeCN アセトニトリル
DCM ジクロロメタン
(付記)
(付記1)
化合物
(付記2)
前記3-ヒドロキシ-4-メトキシチオフェノールが、2-メトキシフェニルアセテートから調製される、付記1に記載の方法。
(付記3)
前記3-ヒドロキシ-4-メトキシチオフェノールが、
(付記4)
示された構造が、対応するジベンゾイル-L-酒石酸塩として調製される、付記3に記載の方法。
(付記5)
示された構造が、対応するジ-p-トルオイル-L-酒石酸塩として調製される、付記3に記載の方法。
(付記6)
前記3-ヒドロキシ-4-メトキシチオフェノールが、
次いで、リッター反応によって、
(付記7)
前記リッター反応が、ClCH 2 CNを用いる、付記6に記載の方法。
(付記8)
前記3-ヒドロキシ-4-メトキシチオフェノールが、
(付記9)
前記転換が、前記3-ヒドロキシ-4-メトキシチオフェノールの(R)-2-アンモニオ-2-エチルヘキシルスルフェートとの反応を含む、付記8に記載の方法。
(付記10)
前記3-ヒドロキシ-4-メトキシチオフェノールが、
Claims (8)
- 化合物
3-ヒドロキシ-4-メトキシチオフェノールが、
- 前記3-ヒドロキシ-4-メトキシチオフェノールが、2-メトキシフェニルアセテートから調製される、請求項1に記載の方法。
- 前記化合物
- 前記化合物
- 前記3-ヒドロキシ-4-メトキシチオフェノールが、
次いで、リッター反応によって、
- 前記リッター反応が、ClCH2CNを用いる、請求項5に記載の方法。
- 前記3-ヒドロキシ-4-メトキシチオフェノールが、
- 前記転換が、前記3-ヒドロキシ-4-メトキシチオフェノールの(R)-2-アンモニオ-2-エチルヘキシルスルフェートとの反応を含む、請求項7に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462033181P | 2014-08-05 | 2014-08-05 | |
US62/033,181 | 2014-08-05 | ||
PCT/IB2015/055584 WO2016020785A1 (en) | 2014-08-05 | 2015-07-23 | Synthesis of benzothiazepines |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017523212A JP2017523212A (ja) | 2017-08-17 |
JP6543330B2 true JP6543330B2 (ja) | 2019-07-10 |
Family
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Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017506266A Active JP6543330B2 (ja) | 2014-08-05 | 2015-07-23 | ベンゾジアゼピンの合成 |
Country Status (11)
Country | Link |
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US (1) | US9834529B2 (ja) |
EP (1) | EP3177600B1 (ja) |
JP (1) | JP6543330B2 (ja) |
KR (1) | KR20170039195A (ja) |
CN (1) | CN106687451B (ja) |
AU (1) | AU2015298377B2 (ja) |
BR (1) | BR112017002139B1 (ja) |
CA (1) | CA2956833C (ja) |
ES (1) | ES2682171T3 (ja) |
RU (1) | RU2017105217A (ja) |
WO (1) | WO2016020785A1 (ja) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
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RU2019100575A (ru) * | 2016-06-27 | 2020-07-28 | ГлаксоСмитКлайн Интеллекчуал Проперти (N2) Лимитед | Способы синтеза |
CN114096268A (zh) | 2019-02-12 | 2022-02-25 | 米鲁姆制药公司 | 用于增加患有胆汁淤积性肝病的儿科受试者的生长的方法 |
WO2022084212A1 (en) | 2020-10-20 | 2022-04-28 | Glaxosmithkline Intellectual Property (No.2) Limited | Methods for treating cholestatic pruritus |
JP2024501814A (ja) | 2020-12-23 | 2024-01-16 | グラクソスミスクライン、インテレクチュアル、プロパティー、(ナンバー2)、リミテッド | リネリキシバットの形態 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL108634A0 (en) | 1993-02-15 | 1994-05-30 | Wellcome Found | Hypolipidaemic heterocyclic compounds, their prepatation and pharmaceutical compositions containing them |
ZA956647B (en) | 1994-08-10 | 1997-02-10 | Wellcome Found | Hypolipidaemic compounds. |
JO3131B1 (ar) | 2010-04-27 | 2017-09-20 | Glaxosmithkline Llc | مركبات كيميائية |
-
2015
- 2015-07-23 AU AU2015298377A patent/AU2015298377B2/en not_active Ceased
- 2015-07-23 BR BR112017002139-0A patent/BR112017002139B1/pt active IP Right Grant
- 2015-07-23 CA CA2956833A patent/CA2956833C/en active Active
- 2015-07-23 CN CN201580042013.8A patent/CN106687451B/zh active Active
- 2015-07-23 KR KR1020177004500A patent/KR20170039195A/ko unknown
- 2015-07-23 RU RU2017105217A patent/RU2017105217A/ru not_active Application Discontinuation
- 2015-07-23 JP JP2017506266A patent/JP6543330B2/ja active Active
- 2015-07-23 US US15/500,619 patent/US9834529B2/en active Active
- 2015-07-23 EP EP15745248.3A patent/EP3177600B1/en active Active
- 2015-07-23 ES ES15745248.3T patent/ES2682171T3/es active Active
- 2015-07-23 WO PCT/IB2015/055584 patent/WO2016020785A1/en active Application Filing
Also Published As
Publication number | Publication date |
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EP3177600A1 (en) | 2017-06-14 |
CA2956833C (en) | 2022-08-30 |
BR112017002139B1 (pt) | 2021-02-09 |
JP2017523212A (ja) | 2017-08-17 |
US20170210717A1 (en) | 2017-07-27 |
AU2015298377A1 (en) | 2017-02-23 |
US9834529B2 (en) | 2017-12-05 |
CN106687451B (zh) | 2018-11-16 |
BR112017002139A2 (pt) | 2017-11-21 |
AU2015298377B2 (en) | 2017-11-02 |
EP3177600B1 (en) | 2018-05-23 |
RU2017105217A (ru) | 2018-09-06 |
KR20170039195A (ko) | 2017-04-10 |
CA2956833A1 (en) | 2016-02-11 |
RU2017105217A3 (ja) | 2018-11-30 |
WO2016020785A1 (en) | 2016-02-11 |
ES2682171T3 (es) | 2018-09-19 |
CN106687451A (zh) | 2017-05-17 |
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