A simple, efficient method for regioselective synthesis of 7-aminomethyl-7,8-dihydro-6H-quinolin-5-ones, new potential CNS agents

Pita, Beatriz; Masaguer, Christian F.; Raviña, Enrique

doi:10.1016/s0040-4039(00)01780-9

Cited by 18 publications

(18 citation statements)

References 17 publications

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“…We found that the reaction of 1 a with acrolein in the presence of 10 % Pd/C as dehydrogenating agent [12] at 100 8C in toluene afforded the desired unsubstituted pyridosultone system 13 in 18 % yield. This method did not prove to be regioselective when a substituted acrolein was used, in contrast to the results observed in the reaction of 1 a,b with b-keto aldehydes under the aforementioned basic conditions.…”

Section: Chemistrymentioning

confidence: 90%

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From β‐Amino‐γ‐sultone to Unusual Bicyclic Pyridine and Pyrazine Heterocyclic Systems: Synthesis and Cytostatic and Antiviral Activities

et al. 2011

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Herein we describe the first successful application of the β-amino-γ-sultone system as an intermediate for the synthesis of hitherto virtually unknown 3H-[1,2]-oxathiole [4,3-b]pyridine and pyrazine 1,1-dioxide bicyclic heterocyclic systems. All novel compounds were evaluated for their antiviral and cytostatic activities. Compounds 3 a, 15 a, and 21 a inhibited HIV-1-induced cytopathicity. Compound 7 showed remarkable cytostatic activity, and can be regarded as a potential antitumor candidate for further exploration.

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Section: Chemistrymentioning

confidence: 90%

“…Other reaction conditions such as the palladium-catalyzed reaction of 1 a with (E)-but-2-enal in the presence of Pd(PPh 3 ) 4 , 10 % Pd/C, and potassium carbonate [12] did neither improve the yield nor the regioselectivity of the reaction.…”

Section: Chemistrymentioning

confidence: 93%

From β‐Amino‐γ‐sultone to Unusual Bicyclic Pyridine and Pyrazine Heterocyclic Systems: Synthesis and Cytostatic and Antiviral Activities

et al. 2011

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“…When the reaction of 64 take place at C-6, the two tautomers are formed at the same ratio, whereas the condensation at C-3 gives a product for which the equilibrium is shifted towards the enaminone form. 1 H NMR data showed that the keto-enamine form predominated at equilibrium (76%) [47].A convenient method for the synthesis of a series of butyrophenone quinoline derivatives, which were potential CNS agents, includes the preparation of 3-amino-5-methoxymethyl-2-cyclohexen-1-one a potentially useful synthon for the synthesis of other β-substituted cycloalkanones with fused heterocycles containing N as practical ambident nucleophiles [48]. Methylation of hydroxyl group in 1,4-dihydro-3,5-dimethoxy benzyl alcohol, followed by mild acidic hydrolysis of the resulting enolether 67 provided the β-methoxyenone 68.…”

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confidence: 99%

Recent development in preparation reactivity and biological activity of enaminoketones and enaminothiones and their utilization to prepare heterocyclic compounds

Negri

Kascheres

2004

Journal of Heterocyclic Chem

179

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Enaminoketones and esters are gaining increased interest, particularly cyclic-β-enaminoesters, which are known as important intermediates for the synthesis of heterocycles and natural products, because the enantioselective preparation of highly functionalized compounds is of central importance in synthetic chemistry. Enaminones are versatile synthetic intermediates that combine the ambident nucleophilicity of enamines with the ambident eletrophilicity of enones. Enaminoketones and enaminonitriles have proven to be versatile building blocks for the synthesis of various heterocycles such as pyridine, pyrimidine and pyrrole derivatives. Enaminones systems have "enone" character, and may act as acceptors in both 1,2 and 1,4-additions. In this way the enaminone serves as a scaffold for annulation, and can gain access to systems such as pyrroles indolizidines, quinolizidines and perhydroindoles, all of which are common motifs in alkaloid structures. Enaminones are frequently employed as building blocks for the preparation of a variety of bicyclic compounds of biological interest and have been recently recognized as potential anticonvulsant compounds. Since a large number of developments in the use of enaminones in heterocyclic synthesis have occurred, a review of the recent developments in the synthetic approaches, covering the literature since 1995 until 2004, to these interesting molecules and their useful chemical transformations and biological activity can be considered of considerable value.J. Heterocyclic Chem., 41, 461 (2004).Enaminoketones. Introduction.The term enaminone was introduced by Greenhill to define the enamine of a 1,3-diketone, β-ketoester or similar 1,3-difunctional reagents, and is used to indicate any compound containing the conjugated system N-C=C-C=O [1]. Enaminones are versatile synthetic intermediates that combine the ambident nucleophilicity of enamines with the ambident eletrophilicity of enones. The chemistry of the enaminocarbonyl group 1 is potentially an area of considerable scope when one considers that there are present in this moiety, three nucleophilic sites (a, c and e) and two electrophilic sites (b and d) [2][3][4] (Figure 1).Theorically, primary and secondary acyclic enaminones can exist in three tautomeric forms: ketamino form, iminoenol form and oxoimino form [1][2][3]. There is also evidence that cyclic enaminones exist primarily in the enaminoketo form. A study of cyclic enaminoketones shows that these compounds have a significant steric fator in the six-membered ring. The six-membered ring enaminoketones are only slightly stronger bases than the saturated amines, whereas five-and-seven membered rings are much stronger bases than saturated amines. This has been attributed to a large steric strain present in six-membered enaminoketones [5].β-Aminoenones or enaminoketones can exist in four conformations owing to restricted rotations around the C=C double and C-C=O single bonds [3]. Enaminones with primary or secondary amino groups can exist in both Z-and E-forms. If there is a...

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“…The substitution of ÀCH by ÀN in aromatic rings has been one of the most-successful applications of classical isosterism [17]. Thus, as a continuation of our previous work in the synthesis of aza analogues in the pyridine series [18], i.e., bio-isosteric replacement of the benzene ring by a pyrimidine or pyridazine system, was raised. In this paper, we report the synthesis of four novel diaza analogues of 5 and 6, and evaluate their activity against several dopamine and serotonin receptors.…”

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confidence: 99%

“…Synthesis. The synthesis of the cyclohexanedione derivative 7, a key intermediate in our synthetic strategy, has been reported before from 3,5-dimethoxybenzoic acid in a four-step procedure [18]. Our initial purpose was to develop a more-convenient preparation of this intermediate.…”

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confidence: 99%

Synthesis and Biological Evaluation of New Quinazoline and Cinnoline Derivatives as Potential Atypical Antipsychotics

Alvarado

Barceló

Carro

et al. 2006

C&B

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Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophenone derivatives QF0104B (5) and QF0108B (6) were synthesized (Schemes 2 and 3), and evaluated for their binding affinities (Table) towards the serotonin 5-HT2A and 5-HT2C, and the dopamine D2 receptors. Among the new compounds, the quinazoline derivative 15 (= 7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydroquinazolin-5-one) exhibited the highest affinities towards the serotonin 5-HT2A and dopamine D2 receptors, and it is in the borderline of potential atypical antipsychotics. The cinnoline derivative 23 (= 7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydro-3-methylcinnolin-5-one) displayed high selectivity in its binding profile towards the 5-HT2C compared to both the 5-HT2A and D2 receptors.

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A simple, efficient method for regioselective synthesis of 7-aminomethyl-7,8-dihydro-6H-quinolin-5-ones, new potential CNS agents

Cited by 18 publications

References 17 publications

From β‐Amino‐γ‐sultone to Unusual Bicyclic Pyridine and Pyrazine Heterocyclic Systems: Synthesis and Cytostatic and Antiviral Activities

From β‐Amino‐γ‐sultone to Unusual Bicyclic Pyridine and Pyrazine Heterocyclic Systems: Synthesis and Cytostatic and Antiviral Activities

Recent development in preparation reactivity and biological activity of enaminoketones and enaminothiones and their utilization to prepare heterocyclic compounds

Synthesis and Biological Evaluation of New Quinazoline and Cinnoline Derivatives as Potential Atypical Antipsychotics

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