- Condensed 2-pyrrolidinone-1,2-oxazines from lithium enolate of 1-benzyl-5-oxo-3-pyrrolidinecarboxylic acid and β-aryl, β-nitroenamines
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The reaction of the lithium enolate of 1-benzyl-5-oxo-3-pyrrolidinecarboxylic acid 3 with a series of β-aryl, β-nitroenamines unexpectedly afforded 6-aryl-2-benzyl-4-oxa-1-oxo-3a-methoxycarbonyl-2,5-diazaindenes 9a-d, whose structure was determined by analytical and NMR spectroscopical analysis. The structure of 9b was further confirmed by X-ray analysis. A reasonable mechanism for their formation is given.
- Felluga, Fulvia,Gombac, Valentina,Pitacco, Giuliana,Valentin, Ennio,Zangrando, Ennio,Morganti, Stefano,Rizzato, Egon,Spinelli, Domenico,Petrillo, Giovanni
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- Reductive Alkylation of Tertiary Lactams via Addition of Organocopper (RCu) Reagents to Thioiminium Ions
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A simple procedure for the conversion of tertiary lactams to 2-monoalkylated cyclic amines is described. The reaction sequence involves conversion of a lactam to a thioiminium ion followed by reaction with an organocopper (RCu) reagent and final reduction with triacetoxyborohydride. The reaction is high yielding and shows an excellent functional group tolerance. Its utility is demonstrated by a rapid synthesis of indolizidine 167B. The excellent chemoselectivity of the process, where only monoalkylation products are formed, is rationalized by a mechanism involving the formation of a transient enamine.
- Mateo, Pierre,Cinqualbre, Joséphine E.,Meyer Mojzes, Melinda,Schenk, Kurt,Renaud, Philippe
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supporting information
p. 12318 - 12327
(2017/12/08)
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- Borinic Acid Catalysed Reduction of Tertiary Amides with Hydrosilanes: A Mild and Chemoselective Synthesis of Amines
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A reduction of various aryl, alkyl, and α,β-unsaturated amides with phenylsilane, catalysed by a borinic acid, is reported. The unprecedented reaction was carried out under very mild conditions and led to useful amines. Furthermore, the reaction tolerates a variety of functional groups. Initial investigations implicated that an intermediate diarylhydroborane is involved in the reaction mechanism.
- Chardon, Aurélien,Mohy El Dine, Tharwat,Legay, Rémi,De Paolis, Micha?l,Rouden, Jacques,Blanchet, Jér?me
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supporting information
p. 2005 - 2009
(2017/02/19)
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- A method for preparing west Naira Tanzania
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The invention discloses a preparation method for nebracetam, and belongs to the technical field of medical chemistry. The key points of the technical scheme of the invention are as follows: the preparation method for the nebracetam comprises the following steps: performing Michael addition reaction and intramolecular cyclization on dimethyl itaconate and benzylamine serving as raw materials to obtain 1-benzyl-5-oxopyrrolidin-3-carboxylic methyl ester; reducing the 1-benzyl-5-oxopyrrolidin-3-carboxylic methyl ester by sodium borohydride to obtain 1-benzyl-4-hydroxymethyl-pyrrolidine-2-keton; performing methyl sulfonylation on the 1-benzyl-4-hydroxymethyl-pyrrolidine-2-keton to obtain 1-benzyl-5-oxopyrrolidin-3-carboxylic methanesulfonate; finally, performing ammonification and reduction on the 1-benzyl-5-oxopyrrolidin-3-carboxylic methanesulfonate by using ammonia water to obtain the nebracetam. The preparation method is simple in preparation process, easy to control and high in target product yield, and meets the requirement for green chemistry.
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Paragraph 0030; 0031; 0032; 0033
(2017/08/25)
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- Inhibition of noroviruses by piperazine derivatives
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There is currently an unmet need for the development of small-molecule therapeutics for norovirus infection. The piperazine scaffold, a privileged structure embodied in many pharmacological agents, was used to synthesize an array of structurally-diverse derivatives which were screened for anti-norovius activity in a cell-based replicon system. The studies described herein demonstrate for the first time that functionalized piperazine derivatives possess anti-norovirus activity. Furthermore, these studies have led to the identification of two promising compounds (6a and 9l) that can be used as a launching pad for the optimization of potency, cytotoxicity, and drug-like characteristics.
- Dou, Dengfeng,He, Guijia,Mandadapu, Sivakoteswara Rao,Aravapalli, Sridhar,Kim, Yunjeong,Chang, Kyeong-Ok,Groutas, William C.
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supporting information; experimental part
p. 377 - 379
(2012/02/16)
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- Concise synthesis of bicyclic aminals by way of catalytic intramolecular C-H amination and evaluation of their reactivity as iminium precursors
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The concise synthesis of fused bicyclic aminals by way of intramolecular rhodium-catalyzed C-H amination is reported as well as the evaluation of their reactivity as iminium precursors. In contrast to the well-studied N,O-acetal systems, the aminals synthesized were found to be particularly stable under reaction conditions used for nucleophilic addition.
- Rodriguez-Lucena, David,Morin, Marie S.T.,Compain, Philippe
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scheme or table
p. 155 - 162
(2012/04/04)
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- Synthesis of new β-trifluoromethyl containing GABA and β-fluoromethyl containing N-benzylpyrrolidinones
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A whole series of 3-(mono-, di-, trifluoro)methyl-substituted N-benzylpyrrolidinones 5a-c was synthesized by deoxyfluorination of corresponding 3-functionalized N-benzylpyrrolidinones. New β-trifluoromethyl containing GABA 4a was obtained in two alternative ways: by successive hydrolysis and hydrogenolysis of 3-trifluoromethyl N-benzylpyrrolidinone 5a and from trifluoroacetone as starting compound.
- Gerus, Igor I.,Mironets, Roman V.,Shaitanova, Elena N.,Kukhar, Valery P.
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experimental part
p. 224 - 228
(2010/04/30)
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- Intramolecular 1,6-addition to 2-pyridones. Mechanism and synthetic scope
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Figure presented The scope and limitations of the intramolecular 1,6-addition of an enolate to a 2-pyridone moiety, a reaction that has found application in the synthesis of the lupin alkaloids, have been probed. This nucleophilic addition process has been shown to be reversible and favored in the case of (less stabilized) amide and lactam enolates, which readily form five- and six-membered bi-/tricyclic products. Alternative enolates (ketone, ester, thiolactam) and a variety of different acceptors (isoquinolinone, pyrimidinone, pyrazinone, pyridopyrazinone) have been evaluated, and a range of competing side reactions have been identified and characterized using various techniques, including in situ IR.
- Gallagher, Timothy,Derrick, Ian,Durkin, Patrick M.,Haseler, Claire A.,Hirschhaeuser, Christoph,Magrone, Pietro
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supporting information; experimental part
p. 3766 - 3774
(2010/08/20)
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- Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor
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Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by 1a and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings.
- Iserloh,Pan,Stamford,Kennedy,Zhang,Zhang,Parker,McHugh,Favreau,Strickland,Voigt
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p. 418 - 422
(2008/09/18)
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- Synthesis of pyrrolo[2,3-d][1,2,3]thiadiazole-6-carboxylates via the Hurd-Mori reaction. Investigating the effect of the N-protecting group on the cyclization
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A route to methyl pyrrolo[2,3-d][1,2,3]thiadiazole-6-carboxylates as potential plant activators and inducers of systemic acquired resistance (SAR) is reported. A synthetic strategy based on cyclization of the thiadiazole ring system utilizing thionyl chloride via the Hurd-Mori protocol as key step was developed. Success of the ring closure reaction turned out to be highly dependent on the nature of the N-protecting group of the pyrrolidine precursor. While electron donors such as alkyl gave only poor conversion to the required 1,2,3-thiadiazoles, an electron withdrawing substituent such as methyl carbamate gave superior yields.
- Stanetty, Peter,Turner, Martin,Mihovilovic, Marko D.
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p. 367 - 375
(2007/10/03)
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- Synthesis of functionalized nitrogen heterocycles by radical decarboxylation of β- and γ-amino acids
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Iodinated or oxygenated nitrogen heterocycles are obtained by radical decarboxylation of β- and γ-amino acids. This mild, versatile reaction is applied to the synthesis of bioactive products, such as 4-arylpiperidines, hydroxylated piperidines, and new antifungal agents.
- Boto, Alicia,Hernandez, Rosendo,De Leon, Yolanda,Murguia, Jose R.,Rodriguez-Afonso, Abigail
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p. 673 - 682
(2007/10/03)
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- A chemoenzymatic approach to the synthesis of enantiomerically pure aza analogues of paraconic acid methyl ester and both enantiomers of methyl β-proline
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Enantiopure methyl esters of 1-alkyl-5-oxo-3-pyrrolidinecarboxylic acids were obtained by enzymatic resolution of the corresponding chiral racemic mixtures. A particularly favourable interaction, also supported by molecular mechanics calculations, was observed between the 1-benzyl derivative and α-chymotrypsin, for which the enantiomeric ratio, E, exceeded 200. The absolute configurations of the lactams were determined by means of CD spectroscopy. From the resulting enantiomerically pure (99% e.e.) (S)-(+)-1-benzyl-3-pyrrolidinecarboxylic acid and methyl (R)-(-)-1-benzyl-3-pyrrolidinecarboxylate, the methyl esters of (+) and (-)-β-proline were synthesised in 99% e.e. and 18 and 22% overall yield, respectively.
- Felluga, Fulvia,Pitacco, Giuliana,Prodan, Massimo,Pricl, Sabrina,Visintin, Marco,Valentin, Ennio
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p. 3241 - 3249
(2007/10/03)
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- Arylalkylheterocyclic amines,N-substituted by aryloxyalkyl group in a method for allergy treatment
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A method of inhibiting Type 1 allergic responses in a living animal body with substituted heterocyclic amines is disclosed wherein the active agents are expressed generally by the formula which includes certain known and certain known compounds: STR1 wherein P is zero, one or two; m is one to six inclusive; A is selected from hydrogen, hydroxy or cyano; d is zero or one; Q is --CH--, CH2 -- or STR2 n is zero or one and when Q is --CH-- and n is one, a double bond is formed with one of the adjacent carbons but not both at the same time, and when n and d are zero at the same time, a double bond is formed between the α carbon and a carbon of the central heterocyclic amine ring; Ar, D and R are selected from phenyl, substituted phenyl, pyridinyl, thienyl, furanyl or naphthyl and in addition, R may have the values benzyl, substituted benzyl, cycloalkyl or loweralkyl and D may additionally have the values: 2H-1-benzopyran-2-one,4-oxo-4H-1-benzopyran-2-carboxylic acid loweralkyl ester, 2,3-dihydro-4H-1-benzopyran-4-one, 1,4-benzodioxanloweralkyl-2-yl or 1,1'-biphenyl-4-yl and the pharmaceutically acceptable salts thereof.
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- Synthetic Versatility of N(Silylmethyl)imines: Water-Induced Generation of N-Protonated Azomethine Ylides of Nonstabilized Type and Fluoride-Induced Generation of 2-Azallyl Anions
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N-(Silylmethyl)imines generate N-protonated azomethine ylides of nonstabilized type when treated with water in HMPA, which undergo stereospecific and regioselective cycloadditions with electron-poor olefins affording N-unsubstituted pyrrolidines.On the other hand, fluoride-induced desilylation of the imines leads to 2-azallyl anions which are found to be synthetic equivalents of aminomethyl anion in the Michael additions with electron-poor olefins and nucleophilic additions with carbonyl compounds.
- Tsuge, Otohiko,Kanemasa, Shuji,Hatada, Akira,Matsuda, Koyo
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p. 2537 - 2546
(2007/10/02)
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- Pyrrolidones and process for preparing them
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The present invention relates to pyrrolidone derivatives which are analogous to natural prostaglandins and to a process for preparing the same. The compounds according to the present invention have prostaglandin-like properties and may be used as pharmaceuticals.
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