Title:
PROCESS FOR THE PRODUCTION OF COMPOUNDS HAVING 5- TO 10-MEMBERED AROMATIC HETEROCYCLES WITH ALKYLMAGNESIUM MONOAMIDES
Document Type and Number:
WIPO Patent Application WO/2005/030714
Kind Code:
A1
Abstract:
The invention aims at providing an anionizing agent for heteroaromatic compounds which has the following advantages: (1) the reactivity (degree of anionization) is high, (2) the reaction can be conducted at relatively high temperatures and the formed anion is stable at the relatively high temperatures, (3) the formation of by-products is inhibited, and (4) the safety is satisfactory even in the use on an industrial scale; and a process for the production of heteroaromatic compounds which comprises converting a heteroaromatic compound into an anion by the use of the anionizing agent and reacting the anion with an electrophile to conduct electrophilic substitution. The above aim is attained by reacting a compound having a 5- to 10-membered aromatic heterocycle which may have one to three substituents (such as R10), e.g., a compound [(2)-4’] with a compound represented by the general formula (1) (wherein R1 is C1-6 alkyl; A1 is a group represented by the general formula: -NR2R3 or the like; and R2 and R3 are each C1-6 alkyl having piperazinyl or di(C1-6 alkyl)amino) and reacting the obtained anion with an electrophile. (X)
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Inventors:
KAMADA ATSUSHI (JP)
KUBOTA MANABU (JP)
KUBOTA MANABU (JP)
Application Number:
PCT/JP2004/013910
Publication Date:
April 07, 2005
Filing Date:
September 24, 2004
Export Citation:
Assignee:
EISAI CO LTD (JP)
KAMADA ATSUSHI (JP)
KUBOTA MANABU (JP)
KAMADA ATSUSHI (JP)
KUBOTA MANABU (JP)
International Classes:
C07D209/12; (IPC1-7): C07D209/08; C07D209/12; C07D213/64; C07D213/65; C07D213/69; C07D239/52; C07D241/18; C07D241/44; C07D471/04
Foreign References:
| JPH01275570A | 1989-11-06 |
Other References:
COMINS, D.L. ET AL.: "Ortho lithiation of 2-, 3-, and 4-methoxypyridines", TETRAHEDRON LETTERS, vol. 29, no. 7, 1988, pages 773 - 776, XP002984241
GROS, P. ET AL.: "Lithiation of 2-Chloro-and 2-Methoxypyridine with Lithium Dialkylamides: Initial Ortho-Direction or Subsequent Lithium Ortho-Stabilization?", JOURNAL OF ORGANIC CHEMISTRY, vol. 68, no. 6, March 2003 (2003-03-01), pages 2243 - 2247, XP002984242
LEE, L.F. ET AL.: "Synthesis of 2,4-Dialkoxy-6-(trifluoromethyl)-3,5-pyridinedicarboxylates via a Novel Cyclocondensation of Dialkyl 3-Oxopentanedioates with Trifluoroacetonitrile", JOURNAL OF ORGANIC CHEMISTRY, vol. 55, no. 9, 1990, pages 2964 - 2967, XP002109411
PARRY, P.R. ET AL.: "New shelf-stable halo- and alkoxy-substituted pyridylboronic acids and their Suzuki cross-coupling reactions to yield heteroarylpyridines", SYNTHESIS, no. 7, July 2003 (2003-07-01), pages 1035 - 1038, XP002903323
SCHLECKER, W. ET AL.: "Regioselective Metalation of Pyridinylcarbamates and Pyridinecarboxamides with (2,2,6,6-Tetramethylpiperidino)magnesium Chloride", JOURNAL OF ORGANIC CHEMISTRY, vol. 60, 1995, pages 8414 - 8416, XP000983659
SCHLECKER, W. ET AL.: "Regioselective Monometalation of 2,5-Pyridinedicarboxamides with (2,2,6,6-Tetramethylpiperidino)magnesium Chloride (TMPMgC1)", LIEBIGS ANN, 1995, pages 1441 - 1446, XP000942101
MATTSON, R.J. ET AL.: "Ortho-Directed Lithiation in pi-Deficient Diazinyl Heterocycles", JOURNAL OF ORGANIC CHEMISTRY, vol. 55, no. 10, 1990, pages 3410 - 3412, XP002984243
ZHANG, M. ET AL.: "BuMgNiPr2: A New Base for Stoichiometric, Position-Selective Deprotonation of Cyclopropane Carboxamides and Other Weak CH Acids", ANGEW.CHEM.INT.ED., vol. 41, no. 12, 2002, pages 2169 - 2171, XP002984244
KANAI, M. ET AL.: "Catalytic Enantioselective Conjugate Addition of Grignard Reagents to Cyclic alpha,beta-Unsaturated Carbonyl Compounds", TETRAHEDRON, vol. 55, 1999, pages 3843 - 3854, XP004161050
ASHBY, E.C. ET AL.: "Stereoselective Alkylation of Cyclic Ketones by Dialkylamino- and Arylozy(methyl)magnesium Compounds", JOURNAL OF ORGANIC CHEMISTRY, vol. 43, no. 21, 1978, pages 4094 - 4098, XP002984245
ASHBY, E.C. ET AL.: "A New, Convenient, and Steospecific Method for the Conversion of Secondary Amines to Primary Amines and Olefins. Thermal Decomposition of Magnesium, Zinc, and Aluminum Amides", JOURNAL OF ORGANIC CHEMISTRY, vol. 43, no. 25, 1978, pages 4750 - 4758, XP002984246
GROS, P. ET AL.: "Lithiation of 2-Chloro-and 2-Methoxypyridine with Lithium Dialkylamides: Initial Ortho-Direction or Subsequent Lithium Ortho-Stabilization?", JOURNAL OF ORGANIC CHEMISTRY, vol. 68, no. 6, March 2003 (2003-03-01), pages 2243 - 2247, XP002984242
LEE, L.F. ET AL.: "Synthesis of 2,4-Dialkoxy-6-(trifluoromethyl)-3,5-pyridinedicarboxylates via a Novel Cyclocondensation of Dialkyl 3-Oxopentanedioates with Trifluoroacetonitrile", JOURNAL OF ORGANIC CHEMISTRY, vol. 55, no. 9, 1990, pages 2964 - 2967, XP002109411
PARRY, P.R. ET AL.: "New shelf-stable halo- and alkoxy-substituted pyridylboronic acids and their Suzuki cross-coupling reactions to yield heteroarylpyridines", SYNTHESIS, no. 7, July 2003 (2003-07-01), pages 1035 - 1038, XP002903323
SCHLECKER, W. ET AL.: "Regioselective Metalation of Pyridinylcarbamates and Pyridinecarboxamides with (2,2,6,6-Tetramethylpiperidino)magnesium Chloride", JOURNAL OF ORGANIC CHEMISTRY, vol. 60, 1995, pages 8414 - 8416, XP000983659
SCHLECKER, W. ET AL.: "Regioselective Monometalation of 2,5-Pyridinedicarboxamides with (2,2,6,6-Tetramethylpiperidino)magnesium Chloride (TMPMgC1)", LIEBIGS ANN, 1995, pages 1441 - 1446, XP000942101
MATTSON, R.J. ET AL.: "Ortho-Directed Lithiation in pi-Deficient Diazinyl Heterocycles", JOURNAL OF ORGANIC CHEMISTRY, vol. 55, no. 10, 1990, pages 3410 - 3412, XP002984243
ZHANG, M. ET AL.: "BuMgNiPr2: A New Base for Stoichiometric, Position-Selective Deprotonation of Cyclopropane Carboxamides and Other Weak CH Acids", ANGEW.CHEM.INT.ED., vol. 41, no. 12, 2002, pages 2169 - 2171, XP002984244
KANAI, M. ET AL.: "Catalytic Enantioselective Conjugate Addition of Grignard Reagents to Cyclic alpha,beta-Unsaturated Carbonyl Compounds", TETRAHEDRON, vol. 55, 1999, pages 3843 - 3854, XP004161050
ASHBY, E.C. ET AL.: "Stereoselective Alkylation of Cyclic Ketones by Dialkylamino- and Arylozy(methyl)magnesium Compounds", JOURNAL OF ORGANIC CHEMISTRY, vol. 43, no. 21, 1978, pages 4094 - 4098, XP002984245
ASHBY, E.C. ET AL.: "A New, Convenient, and Steospecific Method for the Conversion of Secondary Amines to Primary Amines and Olefins. Thermal Decomposition of Magnesium, Zinc, and Aluminum Amides", JOURNAL OF ORGANIC CHEMISTRY, vol. 43, no. 25, 1978, pages 4750 - 4758, XP002984246
Attorney, Agent or Firm:
Inami, Minoru (INABA & INAMI Hanabishi Imas Hirakawacho
Building 4th Floor, 3-11, Hirakawacho 2-chome, Chiyoda-k, Tokyo 93, JP)
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