- A convenient synthesis of 4(5)-alkylacyl-1H-imidazoles from 4(5)-imidazolecarboxaldehyde
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A convenient synthesis of 4(5)-acyl-1H-imidazoles from 4(5)-imidazolecarboxaldehyde without N-protecting group is described. 4(5)-Cyanoimidazole could be synthesized from commercially available 4(5)-imidazolecarboxaldehyde in one-pot. Treatment of 4(5)-cyanoimidazole with various alkylmagnesium bromides followed by addition of aqueous sulfuric acid afforded 4(5)-acyl-1H-imidazoles in good yield.
- Kawakami, Jun-Ichi,Kimura, Kazuhiro,Yamaoka, Masayoshi
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- Cyano-substituted 2-carboxyimidazoles: Synthesis of 4-cyano-1-{[2- (trimethylsilyl)ethoxy]methyl}-1H-imidazole-2-carboxylate potassium salt
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The first example of a monocyano-substituted 2-carboxyimidazole is reported. A synthesis of potassium 4-cyano-1-{[2-(trimethylsilyl)ethoxy]methyl}- 1H-imidazole-2-carboxylate (2) is demonstrated where the carboxylate group is introduced via bromine-magnesium exchange on a SEM-protected cyanoimidazole followed by reaction with ethyl cyanoformate. The synthesis includes the equilibration of a regioisomeric mixture of SEM-protected imidazoles to give a single product. Georg Thieme Verlag Stuttgart.
- Wall, Mark J.,Schubert, Carsten,Illig, Carl R.
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- Synthesis, ocular effects, and nitric oxide donation of imidazole amidoximes
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Novel 1-R-imidazole-5-amidoximes and 1-R-5-cyano-imidazole-4-amidoximes (R: H, Me, Bn) were prepared from their corresponding nitriles and were tested for their efficacy to lower intraocular pressure (IOP) in rabbits. The ability of these compounds to donate nitric oxide (NO) was studied by observing the stimulation of formation of cyclic guanosine-3′,5′-monophosphate (cGMP) in the incubation of porcine iris-ciliary body. In the incubation experiments, 1-methylimidazole-5-amidoxime and 1(H)-imidazole-4(5)-amidoxime stimulated formation of cGMP indicating NO donating ability of these compounds. 1-Methylimidazole-5-amidoxime lowered IOP significantly after intravitreal injection.
- Oresmaa,Kotikoski,Haukka,Oksala,Pohjala,Vapaatalo,Moilanen,Vainiotalo,Aulaskari
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- ORGANOMETALLIC COMPLEXES, ORGANIC ELECTROLUMINESCENCE DEVICE USING THE SAME AND DISPLAY
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The present invention relates to an organic metal complex, an organic electroluminescence device using the same and a display device, and provided is an organic metal complex indicated as chemical formula 1 below. [Chemical Formula 1] Definition of the chemical formula 1 exists in the application.
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Paragraph 0122; 0123; 0126; 0127
(2020/03/17)
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- Method for preparing 1H-imidazole-4-carbonitrile
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The invention discloses a method for preparing 1H-imidazole-4-carbonitrile, and particularly relates to the technical field of fine chemical product preparation. The method for preparing 1H-imidazole-4-carbonitrile comprises the following steps: step (1) oxidation reaction: performing oxidation on 4-hydroxymethylimidazole to obtain 1H-imidazole-4-carboxaldehyde; step (2) oximation reaction: performing oximation reaction on the 1H-imidazole-4-carboxaldehyde prepared in the step (1) to obtain 4-formaldoximido imidazole; and step (3) dehydration reaction: performing dehydration reaction on the 4-formaldoximido imidazole prepared in the step (2) to obtain 1H-imidazole-4-carbonitrile. The method provided by the invention has the advantages of reducing many steps due to intermediates are not purified from the beginning of the reaction to the end of the process, reducing energy consumption due to high and low temperature equipment is not used, reducing environmental pollution due to acidic wastewater is not generated, and having a high yield of products; the invention proposes a complete process route for synthesizing 1H-imidazole-4-carbonitrile by using 4-hydroxymethylimidazole as a rawmaterial; and the method is simple in process and easy to realize industrial production.
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Paragraph 0032; 0037; 0038
(2019/02/26)
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- A general, practical palladium-catalyzed cyanation of (hetero)aryl chlorides and bromides
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Playing it safe: The nontoxic cyanide source K4[Fe(CN) 6]×3 H2O can be used for the cyanation of (hetero)aryl halides. The application of palladacycle catalysts prevents poisoning during catalyst formation, thereby allowing for low catalyst loadings, fast reaction times, and wide heterocyclic substrate scope.
- Senecal, Todd D.,Shu, Wei,Buchwald, Stephen L.
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supporting information
p. 10035 - 10039
(2013/10/01)
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- PROCESS FOR THE PREPARATION OF CYANO-SUBSTITUTED-NITROGEN-CONTAINING HETEROARYL COMPOUNDS
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The present invention provides compounds and methods that can be used to convert nitrogen-containing-heteroaryl carboxamides to the corresponding nitrogen-containing-heteroaryl nitriles reliably in one step, with high yields and without the need for elaborate purification.
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Page/Page column 12
(2009/12/05)
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- METHOD OF INHIBITING C-KIT KINASE
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A method of reducing or inhibiting kinase activity of C-KIT in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to C-KIT using a compound of the present invention: or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.
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Page/Page column 74-75
(2008/06/13)
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- SUBSTITUTED BIARYLS, PROCESS FOR THEIR MANUFACTURE AND USE THEREOF AS MEDICAMENTS
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The present invention relates to compounds of general formula (I) wherein A, B, L, R1, R2, R3a and R3b are defined as in the specification, the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties.
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Page/Page column 48
(2010/11/30)
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- METHOD OF INHIBITING FLT3 KINASE
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A method of reducing or inhibiting kinase activity of FLT3 in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 using a compound of the present invention (I), or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.
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Page/Page column 146-147
(2010/11/27)
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- A concise synthesis of racemic 1-(6,7-dimethoxy-2-naphthyl)-1-(1H-imidazol- 4-yl)-2-methylpropan-1-ol for a potent C17,20-lyase inhibitor
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The development of a practical and scaleable synthesis of 1-(6,7-dimethoxy-2-naphthyl)-1-(1H-imidazol-4-yl)-2-methylpropan-1-ol (2) is described. Racemate 2 was synthesized from commercially available 4(5)-imidazolecarboxyaldehyde (7) in three steps excluding chromatography. 4(5)-Cyanoimidazole (10) was prepared from 7 in good yield in a one-pot reaction. A Grignard reaction of cyanoimidazole 10 with isopropylmagnesium bromide followed by the addition of aqueous sulfuric acid formed acylimidazole 9. The final racemate 2 was obtained by the direct Grignard reaction of acylimidazole 9 without N-protection. This process was accomplished efficiently to produce 2 in 70% overall yield from 7 in a large-scale synthesis.
- Kawakami, Jun-Ichi,Kimura, Kazuhiro,Yamaoka, Masayoshi
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p. 206 - 209
(2012/12/26)
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- AROMATIC AMIDES AS INHIBITORS OF C-FMS KINASE
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The invention relates to compounds of Formula (I), wherein A, X, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula (I), are also provided.
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Page/Page column 146-147
(2008/06/13)
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- SYNERGISTIC MODULATION OF FLT3 KINASE USING A FLT3 INHIBITOR AND A FARNESYL TRANSFERASE INHIBITOR
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The invention is directed to a method of inhibiting FLT3 tyrosine kinase activity or expression or reducing FLT3 kinase activity or expression in a cell or a subject comprising the administration of a farnesyl transferase inhibitor and a FLT3 kinase inhibitor selected from compounds of Formula I′: Included within the present invention is both prophylactic and therapeutic methods for treating a subject at risk of (or susceptible to) developing a cell proliferative disorder or a disorder related to FLT3.
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Page/Page column 88-89
(2008/06/13)
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- INHIBITORS OF C-FMS KINASE
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The invention is directed to compounds of Formula (I): wherein A, X, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula (I), are also provided.
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Page/Page column 130-131
(2008/06/13)
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- The Synthesis of Heterocycles via Addition-Elimination Reactions of 4- and 5-Aminoimidazoles
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4-Aminoimidazoles 1 undergo addition-elimination reactions with the electrophilic reagents 5-12 to give exclusively N-adducts, which are useful intermediates for further synthetic transformations to novel heterocyclic systems.Diethyl ethoxymethylenemalonate 5 and 4-amino-1-benzylimidazole 1g give the adduct 13g and subsequent acid-catalysed cyclisation gives the imidazopyridine 25 and the heterocyclic mesomeric betaine 26 which undergoes 1,3-dipolar cycloaddition with dimethyl acetylenedicarboxylate to give two products 29 and 30.When the 2-alkyl-4-aminoimidazoles 1b-d are generated in situ in the presence of the reagent 5, signi ficant products are the 5,5'-diimidazoles 15 and a mechanism for this novel transformation is proposed. 4-Amino-3-cyano-imidazopyrimidines 40 and 41 are formed by cyclisation of the N-adducts prepared using ethoxymethylenemalononitriles 6 and 7.Ethoxymethyleneurethane 9 gives the adducts 66 and cyclisation of the parent adduct 66a gives the novel imidazo-1,3,5-triazin-4-one 68a, the potassium salt of which undergoes N-alkylation.The use of the reagents 10-12 leads to novel 4-aminoimidazo-1,3,5-triazine derivatives 72 whose chemical reactions with both electrophilic and nucleophilic reagents are reported. 5-Aminoimidazoles 3 undergo addition-elimination reactions with the electrophilic reagents 5-12 to give N-adducts and/or C-adducts, depending upon the structure of the reagent.These stable addition-elimination products are usually obtained in good yield and are useful intermediates for further synthesis.Reaction of the amines 3 with diethyl ethoxymethylenemalonate 5 gives mainly N-adducts 17 which can be cyclised using phosphoryl chloride to give the versatile 7-chloroimidazopyridines 31.With ethoxymethylenemalononitrile 6 the amines 3 give C-adducts 42.Thermal cyclisa tion of these adducts 42 gives 5-amino-6-cyanoimidazopyridines 43 which are transformed into novel heterocyclic systems including the tricyclic imidazopyridopyrimidines 55.Cyclisation of the adducts obtained using ethoxymethyleneurethane 9 and the N-cyano analogues 10 and 12 provides new synthetic routes to amino-purine derivatives 86 and 87 and hypoxanthines 70.The preference of electrophilic reagents for N- or C-addition to 5-aminoimidazoles 3 is rationalised using Frontier Molecular Orbital theory.
- Al-Shaar, Adnan H. M.,Chambers, Robert K.,Gilmour, David W.,Lythgoe, David J.,McClenaghan, Ian,Ramsden, Christopher A.
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p. 2789 - 2812
(2007/10/02)
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- AN EFFICIENT METHOD FOR THE PREPARATION OF 4(5)- CYANOIMIDAZOLES
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We report herein a direct, cost-effective process for the preparation of 4(5)-cyanoimidazoles from the corresponding 4(5)-imidazolecarboxylates.
- Leone-Bay, Andrea,Glaser, Laurel
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p. 1409 - 1412
(2007/10/02)
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- Reactions of 4-Cyano- and 4-Methylimidazoles with Isocyanates
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4-Cyano- and 4-methylimidazoles reacted with methyl and aryl isocyanates to give exclusively 1-(substituted carbamoyl)-4-cyano- and 4-methylimidazoles, respectively.Refluxing of 1-carbamoyl-4-methylimidazoles in nitrobenzene yielded 2-carbamoyl-4-methylimidazoles through a known migration, whereas the 4-cyano analogues could not be caused to migrate.On the other hand, the treatment of 4-cyano-1-(methylcarbamoyl)imidazole with methyl isocyanate under the basic conditions resulted in the formation of 2-methyl-1-(methylcarbamoylimino)-2,3-dihydro-1H-imidazoimidazol-3-one which must be formed via the migration of the carbamoyl group to another nitrogen followed by the intramolecular cyclization of the newly introduced carbamoyl group with its vic cyano group.
- Mitsuhashi, Keiryo,Itho, Ei-ichi,Kawahara, Takeo,Tanaka, Kiyoshi
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p. 1103 - 1106
(2007/10/02)
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