JP5458093B2 - 3,6−ジヒドロ−1,3,5−トリアジン誘導体の合成法 - Google Patents
3,6−ジヒドロ−1,3,5−トリアジン誘導体の合成法 Download PDFInfo
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- JP5458093B2 JP5458093B2 JP2011509869A JP2011509869A JP5458093B2 JP 5458093 B2 JP5458093 B2 JP 5458093B2 JP 2011509869 A JP2011509869 A JP 2011509869A JP 2011509869 A JP2011509869 A JP 2011509869A JP 5458093 B2 JP5458093 B2 JP 5458093B2
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- 0 C*C1=NC(C)(*)N=C(N)N1 Chemical compound C*C1=NC(C)(*)N=C(N)N1 0.000 description 2
- GFICWFZTBXUVIG-UHFFFAOYSA-N CC(N=C(N)N1)N=C1N(C)C Chemical compound CC(N=C(N)N1)N=C1N(C)C GFICWFZTBXUVIG-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/10—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
で示される化合物、ならびにその薬学的な塩、互変異性体および立体異性体を製造する方法であって、式II:
で示される化合物と、無機および/または有機塩基の存在もしくは不在下、極性溶媒または溶媒混合物中で反応させ、ここで、該塩基がK2CO3、NaHCO3、NaOMe、Na2CO3、ピペリジン、モルホリンの群から選択されることを特徴とする方法に関する。
で示される化合物、ならびにその薬学的な塩、互変異性体および立体異性体を製造する方法であって、式II:
で示される化合物と、無機および/または有機塩基の存在下、極性溶媒または溶媒混合物中で反応させ、該塩基がK2CO3、NaHCO3、NaOMe、Na2CO3、ピペリジン、モルホリンの群から選択されることを特徴とする方法である。
2−アミノ−3,6−ジヒドロ−4−ジメチルアミノ−6−メチル−1,3,5−トリアジンの製造:
メタノール50ml中のN,N−ジメチルビグアニド塩酸塩10g(60mmol)の懸濁液を0〜−5℃に冷却した。NaOMe溶液(メタノール中30%)5.3g(120mmol)および10.9g(60mmol)を加えた。20時間後のHPLCは、所望の生成物への転換を示した。
1H NMR (300 MHz, CDCl3) δ 1.37 (d, J = 6.0 Hz, 3H), 2.98 (s, 6H), 3.46 (s, 1H), 4.83 (q, J = 6.0 Hz, 1H)。13C NMR (300 MHz, CDCl3) δ 24.5, 36.4, 63.0。
2−アミノ−3,6−ジヒドロ−4−ジメチルアミノ−6−(4−ヒドロキシフェニル)−1,3,5−トリアジンの製造:
イソプロパノール300ml中のN,N−ジメチルビグアニド30.42g(0.235mol)、p−ヒドロベンズアルデヒド30.2g(0.246mol)およびピペリジン3mlの懸濁液を、還流にて20時間撹拌した。冷却すると固体の沈殿を生じ、これを回収し、冷イソプロパノールで洗浄した。収量:42g、2−アミノ−3,6−ジヒドロ−4−ジメチルアミノ−6−(4−ヒドロキシフェニル)−1,3,5−トリアジン。
Claims (11)
- Rが、メチルまたは4−ヒドロキシフェニルである、請求項1記載の方法。
- 塩基が、NaOMeまたはピペリジンの群から選択される、請求項1または2記載の方法。
- 溶媒が、水、メタノール、エタノール、イソプロパノール、n−ブタノール、2−ブタノール、i−ブタノール、t−ブタノール、N,N−ジメチルホルムアミドの群から単独の溶媒または溶媒混合物として選択される、請求項1〜3のいずれか1項記載の方法。
- 式IIの化合物の濃度が、0.1〜4mol/Lである、請求項1〜4のいずれか1項記載の方法。
- 式IIIの化合物が、式IIの化合物に対して1〜10当量である、請求項1〜5のいずれか1項記載の方法。
- 塩基が、式IIの化合物に対して0.9〜10当量である、請求項1〜6のいずれか1項記載の方法。
- 式IIIの化合物が、アセトアルデヒドである、請求項1〜7のいずれか1項記載の方法。
- 反応が、周囲圧力下、−10〜80℃の温度で実施される、請求項1〜8のいずれか1項記載の方法。
- 反応が、周囲圧力下、−5〜60℃の温度で実施される、請求項1〜9のいずれか1項記載の方法。
- 反応が、周囲圧力下、−5〜20℃の温度で実施される、請求項1〜10のいずれか1項記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP08009483 | 2008-05-23 | ||
EP08009483.2 | 2008-05-23 | ||
PCT/EP2009/002997 WO2009141040A2 (en) | 2008-05-23 | 2009-04-24 | Process for the synthesis of 3,6-dihydro-1,3,5-triazine derivatives |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2011520930A JP2011520930A (ja) | 2011-07-21 |
JP2011520930A5 JP2011520930A5 (ja) | 2012-05-24 |
JP5458093B2 true JP5458093B2 (ja) | 2014-04-02 |
Family
ID=40791625
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011509869A Expired - Fee Related JP5458093B2 (ja) | 2008-05-23 | 2009-04-24 | 3,6−ジヒドロ−1,3,5−トリアジン誘導体の合成法 |
Country Status (21)
Country | Link |
---|---|
US (1) | US20110124860A1 (ja) |
EP (1) | EP2300444B1 (ja) |
JP (1) | JP5458093B2 (ja) |
KR (1) | KR101618198B1 (ja) |
CN (1) | CN102036970A (ja) |
AU (1) | AU2009250149B2 (ja) |
BR (1) | BRPI0912512B1 (ja) |
CA (1) | CA2725011A1 (ja) |
CY (1) | CY1117855T1 (ja) |
DK (1) | DK2300444T3 (ja) |
EA (1) | EA018921B1 (ja) |
ES (1) | ES2571793T3 (ja) |
HR (1) | HRP20160414T1 (ja) |
HU (1) | HUE027532T2 (ja) |
IL (1) | IL209198A (ja) |
MX (1) | MX2010012741A (ja) |
PL (1) | PL2300444T3 (ja) |
RS (1) | RS54736B1 (ja) |
SI (1) | SI2300444T1 (ja) |
WO (1) | WO2009141040A2 (ja) |
ZA (1) | ZA201009160B (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EA022300B1 (ru) | 2010-12-01 | 2015-12-30 | Поксел | Разделение энантиомеров 2-амино-3,6-дигидро-4-диметиламино-6-метил-1,3,5-триазина с использованием винной кислоты |
CN105753801B (zh) * | 2016-03-25 | 2018-06-01 | 浙江工业大学 | 一种均三嗪类化合物的制备方法 |
KR20200102982A (ko) | 2017-10-02 | 2020-09-01 | 폭셀 | 보존된 박출률을 갖는 심부전의 치료 방법 |
CA3103324A1 (en) | 2018-06-14 | 2019-12-19 | Poxel | Film-coated tablet comprising a triazine derivative for use in the treatment of diabetes |
CN114681464A (zh) * | 2020-12-28 | 2022-07-01 | 南京理工大学 | 二甲双胍类似物在制备脑缺血再灌注损伤预防和治疗药物中的应用 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2804113B1 (fr) * | 2000-01-26 | 2004-06-18 | Lipha | Derives animes de dihydro-1,3,5-triazine et leurs applications en therapeutique |
JP4391422B2 (ja) * | 2002-12-17 | 2009-12-24 | 浜理薬品工業株式会社 | 新規2,4−ジアミノ−1,3,5−トリアジン誘導体 |
FR2853650B1 (fr) * | 2003-04-10 | 2006-07-07 | Merck Sante Sas | Procede de dedoublement d'amines utiles pour le traitement de desordres associes au syndrome d'insulino-resistance |
DE102007054416A1 (de) * | 2007-11-13 | 2009-05-14 | Studiengesellschaft Kohle Mbh | Verfahren zur Herstellung von 3,6-Dihydro-1,3,5- Triazin-Derivaten für die Behandlungen von Erkrankungen, die mit dem Insulinresistenz-Syndrom assoziiert sind |
-
2009
- 2009-04-24 US US12/736,856 patent/US20110124860A1/en not_active Abandoned
- 2009-04-24 EP EP09749530.3A patent/EP2300444B1/en active Active
- 2009-04-24 BR BRPI0912512A patent/BRPI0912512B1/pt not_active IP Right Cessation
- 2009-04-24 CA CA2725011A patent/CA2725011A1/en not_active Abandoned
- 2009-04-24 RS RS20160296A patent/RS54736B1/sr unknown
- 2009-04-24 DK DK09749530.3T patent/DK2300444T3/en active
- 2009-04-24 SI SI200931424A patent/SI2300444T1/sl unknown
- 2009-04-24 ES ES09749530T patent/ES2571793T3/es active Active
- 2009-04-24 CN CN2009801188956A patent/CN102036970A/zh active Pending
- 2009-04-24 JP JP2011509869A patent/JP5458093B2/ja not_active Expired - Fee Related
- 2009-04-24 PL PL09749530T patent/PL2300444T3/pl unknown
- 2009-04-24 MX MX2010012741A patent/MX2010012741A/es active IP Right Grant
- 2009-04-24 AU AU2009250149A patent/AU2009250149B2/en not_active Ceased
- 2009-04-24 HU HUE09749530A patent/HUE027532T2/en unknown
- 2009-04-24 WO PCT/EP2009/002997 patent/WO2009141040A2/en active Application Filing
- 2009-04-24 KR KR1020107028733A patent/KR101618198B1/ko active IP Right Grant
- 2009-04-24 EA EA201001828A patent/EA018921B1/ru not_active IP Right Cessation
-
2010
- 2010-11-08 IL IL209198A patent/IL209198A/en active IP Right Grant
- 2010-12-21 ZA ZA2010/09160A patent/ZA201009160B/en unknown
-
2016
- 2016-04-20 HR HRP20160414TT patent/HRP20160414T1/hr unknown
- 2016-05-11 CY CY20161100394T patent/CY1117855T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
CY1117855T1 (el) | 2017-05-17 |
AU2009250149A1 (en) | 2009-11-26 |
WO2009141040A3 (en) | 2010-01-21 |
KR20110013498A (ko) | 2011-02-09 |
EA201001828A1 (ru) | 2011-04-29 |
AU2009250149B2 (en) | 2013-05-23 |
EA018921B1 (ru) | 2013-11-29 |
RS54736B1 (sr) | 2016-10-31 |
EP2300444B1 (en) | 2016-04-13 |
SI2300444T1 (sl) | 2016-10-28 |
DK2300444T3 (en) | 2016-05-23 |
BRPI0912512B1 (pt) | 2018-09-11 |
EP2300444A2 (en) | 2011-03-30 |
BRPI0912512A2 (pt) | 2015-07-28 |
KR101618198B1 (ko) | 2016-05-04 |
IL209198A (en) | 2013-11-28 |
MX2010012741A (es) | 2010-12-21 |
ZA201009160B (en) | 2011-10-26 |
US20110124860A1 (en) | 2011-05-26 |
WO2009141040A2 (en) | 2009-11-26 |
JP2011520930A (ja) | 2011-07-21 |
HRP20160414T1 (hr) | 2016-05-20 |
PL2300444T3 (pl) | 2016-08-31 |
ES2571793T3 (es) | 2016-05-26 |
IL209198A0 (en) | 2011-01-31 |
HUE027532T2 (en) | 2016-10-28 |
CA2725011A1 (en) | 2009-11-26 |
CN102036970A (zh) | 2011-04-27 |
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