WO2013117610A1 - Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives - Google Patents
Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives Download PDFInfo
- Publication number
- WO2013117610A1 WO2013117610A1 PCT/EP2013/052362 EP2013052362W WO2013117610A1 WO 2013117610 A1 WO2013117610 A1 WO 2013117610A1 EP 2013052362 W EP2013052362 W EP 2013052362W WO 2013117610 A1 WO2013117610 A1 WO 2013117610A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pyridine
- phenyl
- triazolo
- mmol
- formula
- Prior art date
Links
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
- C07D471/04—Ortho-condensed systems
Definitions
- the invention relates to a novel process for the preparation of 2-phenyl-[l,2,4]triazolo[l,5- a]pyridine derivatives of formula I or of a salt thereof
- R stands for hydrogen, a halogen, for an optionally protected hydroxyl group or for an optionally protected amino group and
- R is hydrogen or a halogen.
- Object of the present invention therefore was to find a synthesis which is applicable on large scale and which is free from the drawbacks encountered in the synthesis known from the state of the art.
- R stands for hydrogen, a halogen, for an optionally protected hydroxyl group or for an optionally protected amino group and
- R is hydrogen or a halogen, the process which comprises the conversion of a pyridine compound of formula II or of a salt thereof,
- R 1 and 2 are as above, with benzonitrile in the presence of a Cu-catalyst, a 1,10- phenanthroline derivative and of a mixture 0 2 /N 2 , characterized in that no other solvent than the reactant benzonitrile is present in the process.
- salt embraces salts of the compounds of formula I with inorganic or organic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulphuric acid, phosphoric acid, citric acid, formic acid, maleic acid, acetic acid, fumaric acid, succinic acid, tartaric acid, methanesulphonic acid, salicylic acid, p-toluenesulphonic acid, trifluoroacetic acid and the like.
- Preferred salts with acids are formates, maleates, citrates, hydrochlorides, hydrobromides and methanesulfonic acid salts, with hydrochlorides and hydrobromides being especially preferred.
- protected amino group refers to an amino group protected with any substituents conventionally used to hinder the reactivity of the amino group.
- Suitable amino protecting groups are described in Green T., “Protective Groups in Organic Synthesis", 4 th Ed. by Wiley Interscience, 2007, Chapter 7, 696 ff..
- Suitable amino protecting groups can be selected from Boc, Fmoc, Cbz, Moz, Troc, Teoc or Voc, more particularly Boc is used.
- protected hydroxyl group refers to a hydroxyl group protected with any substituents conventionally used to hinder the reactivity of the hydroxyl group. Suitable hydroxy protecting groups are described in Green T., “Protective Groups in Organic Synthesis", 4th Ed. by Wiley Interscience, 2007, Chapter 2, 16 ff.. Suitably trifluoromethylsulfonyl (Tf),
- TMS trimethylsilyl
- Bn benzyl
- halogen refers to chlorine, bromine or iodine.
- R 1 and R 2 are as above are as a rule commercially available compounds, otherwise they are accessible with synthetic methods well known to the skilled in the art.
- R 1 stands for a halogen and R 2 for hydrogen, more particularly R 1 stands for bromine.
- the process of the present invention is characterized in that the reactant benzonitrile is the sole solvent and that no additional solvent is used.
- the reaction is further characterized in that the reaction temperature is selected between
- 80°C and 170°C in a more particular embodiment between 110°C and 150°C and even more particular at about 130°C.
- the reaction pressure can be selected between 1 and 100 bar. In a more particular embodiment the pressure is selected between 1 and 60 bar and even more particular between 1 and 20 bar.
- the concentration of the pyridine compound of formula II in benzonitrile can be chosen between 2 wt. % and 30 wt. %.
- the concentration of the pyridine compound of formula II in benzonitrile is between 5 wt.% and 20 wt.%, even more particular between 7 wt.% and 15 wt.%.
- the process can be performed with mixtures 0 2 /N 2 having an 0 2 content of 1 Vol % to 21 Vol % 0 2 . It is hereby understood that the mixtures 0 2 /N 2 as defined before include air. In a more particular embodiment the 0 2 content in the mixture 0 2 /N 2 is between 3 Vol % and 8 Vol % 0 2 , even more particular between 5 Vol % and 8 Vol % 0 2 .
- the process of the present invention is characterized in that a Cu-catalyst is present.
- CuBr is selected in case R 1 in the pyridine compound of formula II stands for bromine, for an optionally protected hydroxyl group or for an optionally protected amino group. CuBr is also selected in case R 1 in the pyridine compound of formula II stands for hydrogen and R for bromine or hydrogen.
- CuCl is selected in case R 1 in the pyridine compound of formula II stands for chlorine and Cul is selected in case R 1 in the pyridine compound of formula II stands for iodine.
- R in the pyridine compound of formula II stands for bromine the Cu-catalyst is CuBr.
- the Cu-catalyst is as a rule applied in amounts of 0.1 mol % to 20 mol , more
- the process of the present invention is further characterized in that a 1,10 phenanthroline derivative is present.
- a 1,10 phenanthroline derivative is present.
- the commercially available monohydrate of 1,10 phenanthroline is used.
- the 1,10 phenanthroline derivative is as a rule applied in amounts of 0.1 mol to 20 mol , more particularly in amounts of 1 mol % to 5 mol % related to the pyridine compound of formula II.
- reaction time can vary with the reaction parameters selected, as a rule the reaction is completed after about 20h to 30h.
- Isolation of the desired 2-phenyl-[l,2,4]triazolo[l,5-a]pyridine derivative of formula I from the reaction mixture can as a rule happen by filtration. Further purification of the crude product may happen by charcoal treatment of a solution of the product e.g. in a suitable solvent like ethylacetate and by subsequent crystallization.
- Retention time 2.25 min (2-amino-4-bromopyridine), 3.00 min (N-(4-bromo-pyridin-2-yl)-benzamidine), 6.40 min (7- bromo-2-phenyl-[l,2,4]triazolo[l,5-a]pyridine), 6.62 min (7-iodo-2-phenyl-[l,2,4]triazolo[l,5- a]pyridine)).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MX2014008814A MX348447B (en) | 2012-02-09 | 2013-02-07 | Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyr idine derivatives. |
CA2858778A CA2858778A1 (en) | 2012-02-09 | 2013-02-07 | Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives |
KR1020147022111A KR20140128998A (en) | 2012-02-09 | 2013-02-07 | Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives |
RU2014134278A RU2620379C2 (en) | 2012-02-09 | 2013-02-07 | Method for prepairing derivatives of 2-phenyl [1,2,4] triazolo [1,5-a] pyridine |
JP2014556039A JP6122034B2 (en) | 2012-02-09 | 2013-02-07 | Method for preparing 2-phenyl- [1,2,4] triazolo [1,5-a] pyridine derivative |
CN201380006265.6A CN104093718B (en) | 2012-02-09 | 2013-02-07 | Be used for the method for the preparation of 2-phenyl-[1,2,4] triazols [1,5-a] pyridine derivate |
BR112014016427A BR112014016427A8 (en) | 2012-02-09 | 2013-02-07 | Process for the preparation of 2-phenyl- [1,2,4] triazolo [1,5-a] pyridine derivatives |
ES13702648.0T ES2558618T3 (en) | 2012-02-09 | 2013-02-07 | Process for the preparation of 2-phenyl- [1,2,4] triazolo [1,5-A] pyridine derivatives |
EP13702648.0A EP2812330B1 (en) | 2012-02-09 | 2013-02-07 | Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives |
US14/455,773 US9115130B2 (en) | 2012-02-09 | 2014-08-08 | Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives |
HK14110819.2A HK1197244A1 (en) | 2012-02-09 | 2014-10-29 | Process for the preparation of 2-phenyl-[1,2,4] triazolo [1,5-a] pyridine derivatives 2--[124][15-a] |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP12154786 | 2012-02-09 | ||
EP12154786.3 | 2012-02-09 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US14/455,773 Continuation US9115130B2 (en) | 2012-02-09 | 2014-08-08 | Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013117610A1 true WO2013117610A1 (en) | 2013-08-15 |
Family
ID=47664298
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2013/052362 WO2013117610A1 (en) | 2012-02-09 | 2013-02-07 | Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives |
Country Status (12)
Country | Link |
---|---|
US (1) | US9115130B2 (en) |
EP (1) | EP2812330B1 (en) |
JP (1) | JP6122034B2 (en) |
KR (1) | KR20140128998A (en) |
CN (1) | CN104093718B (en) |
BR (1) | BR112014016427A8 (en) |
CA (1) | CA2858778A1 (en) |
ES (1) | ES2558618T3 (en) |
HK (1) | HK1197244A1 (en) |
MX (1) | MX348447B (en) |
RU (1) | RU2620379C2 (en) |
WO (1) | WO2013117610A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20170032329A (en) | 2014-07-30 | 2017-03-22 | 모찌다 세이야쿠 가부시끼가이샤 | Pyrazole derivative manufacturing method |
KR20170032328A (en) | 2014-07-30 | 2017-03-22 | 모찌다 세이야쿠 가부시끼가이샤 | Pyrazole derivative manufacturing method |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011032225A (en) * | 2009-08-03 | 2011-02-17 | Gifu Ichi | Method for producing 1,2,4-triazole derivative |
WO2012076430A1 (en) * | 2010-12-07 | 2012-06-14 | F. Hoffmann-La Roche Ag | Triazolopyridine compounds |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4358454A (en) * | 1982-01-08 | 1982-11-09 | Schering Corporation | 1,3,4-Triazolo[1,5-a]pyridines |
PL370067A1 (en) * | 2001-10-08 | 2005-05-16 | F.Hoffmann-La Roche Ag | 8-amino-[1,2,4]triazolo[1,5-a]pyridine-6-carboxylic acid amide |
-
2013
- 2013-02-07 ES ES13702648.0T patent/ES2558618T3/en active Active
- 2013-02-07 CA CA2858778A patent/CA2858778A1/en not_active Abandoned
- 2013-02-07 EP EP13702648.0A patent/EP2812330B1/en not_active Not-in-force
- 2013-02-07 CN CN201380006265.6A patent/CN104093718B/en not_active Expired - Fee Related
- 2013-02-07 RU RU2014134278A patent/RU2620379C2/en not_active IP Right Cessation
- 2013-02-07 WO PCT/EP2013/052362 patent/WO2013117610A1/en active Application Filing
- 2013-02-07 JP JP2014556039A patent/JP6122034B2/en active Active
- 2013-02-07 KR KR1020147022111A patent/KR20140128998A/en not_active Application Discontinuation
- 2013-02-07 MX MX2014008814A patent/MX348447B/en active IP Right Grant
- 2013-02-07 BR BR112014016427A patent/BR112014016427A8/en not_active Application Discontinuation
-
2014
- 2014-08-08 US US14/455,773 patent/US9115130B2/en not_active Expired - Fee Related
- 2014-10-29 HK HK14110819.2A patent/HK1197244A1/en not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011032225A (en) * | 2009-08-03 | 2011-02-17 | Gifu Ichi | Method for producing 1,2,4-triazole derivative |
WO2012076430A1 (en) * | 2010-12-07 | 2012-06-14 | F. Hoffmann-La Roche Ag | Triazolopyridine compounds |
Non-Patent Citations (6)
Title |
---|
GREEN T.: "Protective Groups in Organic Synthesis", 2007, WILEY INTERSCIENCE, pages: 16 FF |
GREEN T.: "Protective Groups in Organic Synthesis", 2007, WILEY INTERSCIENCE, pages: 696 FF |
J.AM.CHEM.SOC., vol. 131, 2009, pages 15080 - 15081 |
JACS, vol. 131, 2009, pages 15080 - 15081 |
NAGASAWA ET AL., J.AM.CHEM.SOC., vol. 131, 2009, pages 15080 - 15081 |
SATOSHI UEDA AND HIDEKO NAGASAWA: "Facile Synthesis of 1,2,4-Triazoles via a Copper-Catalyzed Tandem Addition-Oxidative Cyclization", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 131, no. 42, 2009, pages 15080 - 15081, XP055055624, ISSN: 0002-7863, DOI: 10.1021/ja905056z * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20170032329A (en) | 2014-07-30 | 2017-03-22 | 모찌다 세이야쿠 가부시끼가이샤 | Pyrazole derivative manufacturing method |
KR20170032328A (en) | 2014-07-30 | 2017-03-22 | 모찌다 세이야쿠 가부시끼가이샤 | Pyrazole derivative manufacturing method |
JPWO2016017711A1 (en) * | 2014-07-30 | 2017-06-01 | 持田製薬株式会社 | Method for producing pyrazole derivative |
US20170210740A1 (en) * | 2014-07-30 | 2017-07-27 | Mochida Pharmaceutical Co., Ltd. | Pyrazole derivative manufacturing method |
US9879009B2 (en) | 2014-07-30 | 2018-01-30 | Mochida Pharmaceutical Co., Ltd. | Pyrazole derivative manufacturing method |
US9902723B2 (en) | 2014-07-30 | 2018-02-27 | Mochida Pharmaceutical Co., Ltd. | Pyrazole derivative manufacturing method |
US10174025B2 (en) | 2014-07-30 | 2019-01-08 | Mochida Pharmaceutical Co., Ltd. | Pyrazole derivative manufacturing method |
Also Published As
Publication number | Publication date |
---|---|
EP2812330A1 (en) | 2014-12-17 |
ES2558618T3 (en) | 2016-02-05 |
CN104093718B (en) | 2016-05-04 |
HK1197244A1 (en) | 2015-01-09 |
EP2812330B1 (en) | 2015-12-02 |
MX2014008814A (en) | 2014-10-24 |
KR20140128998A (en) | 2014-11-06 |
CA2858778A1 (en) | 2013-08-15 |
US20140350259A1 (en) | 2014-11-27 |
MX348447B (en) | 2017-06-13 |
BR112014016427A8 (en) | 2017-07-04 |
RU2014134278A (en) | 2016-03-27 |
CN104093718A (en) | 2014-10-08 |
US9115130B2 (en) | 2015-08-25 |
RU2620379C2 (en) | 2017-05-25 |
JP2015511235A (en) | 2015-04-16 |
JP6122034B2 (en) | 2017-04-26 |
BR112014016427A2 (en) | 2017-06-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102026059B1 (en) | Method for producing substituted 5-fluoro-1h-pyrazolopyridines | |
AU2008298943B2 (en) | Process and intermediates for preparing integrase inhibitors | |
JP6061158B2 (en) | Synthesis intermediate of 6- (7-((1-aminocyclopropyl) methoxy) -6-methoxyquinolin-4-yloxy) -N-methyl-1-naphthamide, or a pharmaceutically acceptable salt thereof, and its use | |
US9133188B2 (en) | Methods for preparing naphthyridines | |
WO2013119328A1 (en) | Solid state forms of apixaban | |
RU2663834C2 (en) | Palladium-catalysed coupling of pyrazole amides | |
US9115130B2 (en) | Process for the preparation of 2-phenyl-[1,2,4]triazolo[1,5-a]pyridine derivatives | |
BG99490A (en) | 5-vinyl(ethynyl)quinolon(naphthyrridon)carboxylic acids | |
EP3706740A1 (en) | Processes to produce acalabrutinib | |
AU2007228939A1 (en) | Process for preparing l-halo-2,7-naphthyridinyl derivatives | |
KR20230026411A (en) | Method for producing aromatic ether compounds | |
CN111808121A (en) | Novel high-B-ring berberine analogue containing heteroatom and C-H activation synthesis method thereof | |
JP7279134B2 (en) | Method for producing prolinamide compound | |
JP6997769B2 (en) | Method for producing 2- (6-nitropyridin-3-yl) -9H-dipyrido [2,3-b; 3', 4'-d] pyrrole | |
KR20220101702A (en) | Manufacturing process of chroman compounds | |
CN111349044A (en) | Aromatic amine derivative synthesized by deconstruction of azaarene, and method and application thereof | |
JP2023100917A (en) | Method for producing prolinamide compound | |
KR20240007121A (en) | Synthetic methods and intermediates for producing compounds for treating KIT- and PDGFRA-mediated diseases | |
EP1179532A1 (en) | Process for the production of indole derivatives and intermediates therefor | |
CN107365299A (en) | A kind of Preparation Method And Their Intermediate of dabigatran etcxilate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 201380006265.6 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 13702648 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 2858778 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2013702648 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: MX/A/2014/008814 Country of ref document: MX |
|
ENP | Entry into the national phase |
Ref document number: 20147022111 Country of ref document: KR Kind code of ref document: A Ref document number: 2014556039 Country of ref document: JP Kind code of ref document: A |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112014016427 Country of ref document: BR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2014134278 Country of ref document: RU |
|
ENP | Entry into the national phase |
Ref document number: 112014016427 Country of ref document: BR Kind code of ref document: A2 Effective date: 20140702 |