WO1999019314A1 - Process for preparing substituted pyrazine compounds - Google Patents
Process for preparing substituted pyrazine compounds Download PDFInfo
- Publication number
- WO1999019314A1 WO1999019314A1 PCT/US1998/021245 US9821245W WO9919314A1 WO 1999019314 A1 WO1999019314 A1 WO 1999019314A1 US 9821245 W US9821245 W US 9821245W WO 9919314 A1 WO9919314 A1 WO 9919314A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- added
- amino
- phenyl
- stirred
- azadiene
- Prior art date
Links
Classifications
-
- 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
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D295/02—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 containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—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 containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—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 containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- 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
- C07D295/04—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
Definitions
- Pyrazine compounds are widely used in the pharmaceutical, chemical, and agricultural fields. Condensation reactions involving reacting malononitrile oximinotosylate with an enamine followed by quenching with ammonia to form 2-amino-3-cyano-6-substituted pyrazines has been reported. Fleury et al., Tetrahedron Letters. 1974, 3967. However, the enamines used in such reactions were prepared from ketones in the presence of ammonia. This preparation lead to synthesis of 6-substituted 2-aminopyrazine compounds. There still is a need for a process of forming 6-unsubstituted 2-substituted pyrazine heterocycles.
- the present invention relates to a process of producing 6-unsubstituted 2-substituted pyrazine heterocycles involving the reaction of an oxime with an enamine.
- the present invention also relates to producing novel intermediates which are useful in producing pyrazine compounds as well as novel substituted pyrazine compounds.
- a pyrazine heterocycle is formed by reacting a secondary amine with an aldehyde to form an enamine.
- the enamine compound is then reacted with an oxime to produce a novel 2-azadiene compound.
- Subsequent quenching with ammonia provides a 2-aminopyrazine.
- the pyrazine may be formed by reacting the 2-azadiene compound with a thiol bearing compound, such as but not intended to be limited to, thioalkyls, thioalkenyls, thioalkynyls, and thioaryls to produce 2-thioalkyl substituted pyrazines and 2-thioaryl substituted pyrazines.
- pyrrolidine (2) is added to phenylacetaldehyde (1) to form the a novel enamine (3).
- Malononitrile oximinotosylate (4) is added to the enamine (3) to form a 2-azadiene intermediate (5).
- the 2-azadiene intermediate (5) is then subsequently quenched with ammonia to provide a 2-amino-3-cyano- hydridopyrazine (8).
- pyrrolidine (2) is added to phenylacetaldehyde (1) to form the a novel enamine (3).
- Malononitrile oximinotosylate (4) is added to the enamine (3) to form a 2-azadiene intermediate (5).
- the 2-azadiene intermediate (5) is then reacted with a thioaryl such as thiophenol (6) to form a novel 3-cyano-5- phenyl-2-phenyIthiopyrazine (7).
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000515887A JP2001519423A (en) | 1997-10-10 | 1998-10-08 | Method for preparing substituted pyrazine compounds |
EP98951005A EP1023278A1 (en) | 1997-10-10 | 1998-10-08 | Process for preparing substituted pyrazine compounds |
CA002305770A CA2305770A1 (en) | 1997-10-10 | 1998-10-08 | Process for preparing substituted pyrazine compounds |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US94905197A | 1997-10-10 | 1997-10-10 | |
US08/949,051 | 1997-10-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999019314A1 true WO1999019314A1 (en) | 1999-04-22 |
Family
ID=25488526
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1998/021245 WO1999019314A1 (en) | 1997-10-10 | 1998-10-08 | Process for preparing substituted pyrazine compounds |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP1023278A1 (en) |
JP (1) | JP2001519423A (en) |
CA (1) | CA2305770A1 (en) |
WO (1) | WO1999019314A1 (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0249775A (en) * | 1988-05-19 | 1990-02-20 | Nippon Soda Co Ltd | Heterocyclic compound having 6-membered or 7-membered ring and production thereof |
WO1998024791A1 (en) * | 1996-12-06 | 1998-06-11 | Abbott Laboratories | Benzopyranopyrrole and benzopyranopyridine alpha-1 adrenergic compounds |
-
1998
- 1998-10-08 WO PCT/US1998/021245 patent/WO1999019314A1/en not_active Application Discontinuation
- 1998-10-08 JP JP2000515887A patent/JP2001519423A/en not_active Withdrawn
- 1998-10-08 EP EP98951005A patent/EP1023278A1/en not_active Withdrawn
- 1998-10-08 CA CA002305770A patent/CA2305770A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0249775A (en) * | 1988-05-19 | 1990-02-20 | Nippon Soda Co Ltd | Heterocyclic compound having 6-membered or 7-membered ring and production thereof |
WO1998024791A1 (en) * | 1996-12-06 | 1998-06-11 | Abbott Laboratories | Benzopyranopyrrole and benzopyranopyridine alpha-1 adrenergic compounds |
Non-Patent Citations (3)
Title |
---|
EDWARD C. TAYLOR: "Pteridines. XXIX. An Unequivocal Route to 2,4-Diamino-6-substituted Pteridines", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY., vol. 95, no. 19, 19 September 1973 (1973-09-19), DC US, pages 6413 - 64118, XP002089656 * |
JOHN E. CRAGG ET AL.: "Phenanthroindozilidine and Related Alkaloids: Synthesis of Tylophorine, Septicine, and Deoxytylophorinine", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1., 1982, LETCHWORTH GB, pages 2477 - 2485, XP002089655 * |
PATENT ABSTRACTS OF JAPAN vol. 014, no. 215 (C - 0716) 8 May 1990 (1990-05-08) * |
Also Published As
Publication number | Publication date |
---|---|
EP1023278A1 (en) | 2000-08-02 |
JP2001519423A (en) | 2001-10-23 |
CA2305770A1 (en) | 1999-04-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5411161B2 (en) | N- {1- [3- (2-Ethoxy-5- (4-ethylpiperazinyl) sulfonylphenyl) -4,5-dihydro-5-oxo-1,2,4-triazin-6-yl] ethyl } Butyramide, its preparation method and use | |
CN114805314A (en) | Synthesis method of Ensaitevir | |
EP0483204B1 (en) | Process for preparing 2,5-diamino-4,6-dichloropyrimidine | |
JPH0245442A (en) | Production of alpha, beta-unsaturated ketone | |
WO1999019314A1 (en) | Process for preparing substituted pyrazine compounds | |
JP2782698B2 (en) | Novel method for producing 9-amino-1,2,3,4-tetrahydroacridine | |
CS203172B2 (en) | Method of producing 2-/4-furoylpiperazin-1-yl-/4-amino-6,7-dimethoxyquinazoline derivatives | |
JP3031279B2 (en) | Method for producing 2-alkoxy-6- (trifluoromethyl) pyrimidin-4-ol | |
MXPA00003506A (en) | Process for preparing substituted pyrazine compounds | |
JP2006528655A (en) | Methods and intermediate compounds useful in the preparation of statins, particularly atorvastatin | |
JPS5949221B2 (en) | Method for producing 3-acylamino-4-homoisotwistane | |
NO783775L (en) | 2,4-DIAMINO-5-BENZYLPYRIMIDINES AND PROCEDURES FOR THE PREPARATION OF THESE | |
JP3602796B2 (en) | Preparation of thiobarbituric acid derivatives | |
JP5396563B1 (en) | N- [1- [3- (2-Ethoxy-5- (4-ethylpiperazinyl) sulfonylphenyl) -4,5-dihydro-5-oxo-1,2,4-triazin-6-yl] ethyl ] Butyramide, its preparation and use | |
WO1990006918A1 (en) | A process for the preparation of 2,4- or 2,4,5-substituted 6-hydroxypyrimidines | |
HU207718B (en) | Process for producing 3,5,6-trichloropyridin-2-ol | |
RU2333908C1 (en) | Method for obtaining 2-ethyl-3,5-dimethylpiridin | |
NO315157B1 (en) | 1-cyano-1-acylaminocyclopentane compounds and process for their preparation | |
US5216160A (en) | Process for the production of 4-amino-2-chloro-5-cyano-6-(methylthio)pyrimidine | |
Campaigne et al. | Synthesis of some amino‐substituted furanopyrimidines and styrylpyrimidines | |
Nishio et al. | Reaction of β-Sulfinyl and β-Sulfenyl α, β-Unsaturated Ketones with Diimines; Preparation of 1, 2-Dihydro-Pyrimidines | |
JPS6210500B2 (en) | ||
SU671726A3 (en) | Method of producing 4-a-aryl-transdecahydro-isoquinolines | |
KR100580940B1 (en) | Process for preparing 2-amino-4-chloro-5-nitro-61H-pyrimidinone | |
EP0163506B1 (en) | Process for the preparation of a pyridil-propanoic acid |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA JP MX |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
ENP | Entry into the national phase |
Ref country code: JP Ref document number: 2000 515887 Kind code of ref document: A Format of ref document f/p: F |
|
ENP | Entry into the national phase |
Ref document number: 2305770 Country of ref document: CA Ref country code: CA Ref document number: 2305770 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1998951005 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2000/003506 Country of ref document: MX |
|
WWP | Wipo information: published in national office |
Ref document number: 1998951005 Country of ref document: EP |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1998951005 Country of ref document: EP |