- The design and synthesis of potent cyclic peptide VCAM-VLA-4 antagonists incorporating an achiral Asp-Pro mimetic
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The Asp-Pro sequence of the cyclic peptide Ac-HN-Tyr-Cys*-Asp-Pro-Cys*-OH (1) could be replaced with the achiral dipeptide mimetic 1-(2-aminoethyl)cyclpentylcarboxylic acid with retention of potent inhibition of the VCAM-VLA-4 interaction. (C) Elsevier Science Ltd. All rights reserved.
- Fotouhi, Nader,Joshi, Pramod,Fry, David,Cook, Charles,Tilley, Jefferson W.,Kaplan, Gerry,Hanglow, Angela,Rowan, Karen,Schwinge, Virginia,Wolitzky, Barry
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Read Online
- SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE
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The present invention provides novel heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof. They are useful in preventing, managing, treating or lessening the severity of a protein kinase-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of protein kinase-mediated disease.
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Paragraph 0433
(2017/04/14)
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- Substituted heteroaryl compound and composition thereof, and uses of substituted heteroaryl compound and composition thereof
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The present invention provides a substituted heteroaryl compound and a composition thereof, and uses of the substituted heteroaryl compound and the composition, wherein the compound is a compound represented by a formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug of the compound represented by the formula (I). The present invention further provides a pharmaceutical composition containing the compound, wherein the pharmaceutical composition can regulate activity of protein kinases, particularly Aurora kinases and JAK kinases, and can be used for prevention, treatment, therapy and alleviation of protein kinases, particularly Aurora kinases and JAK kinase activity mediated diseases or disorders.
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Paragraph 0897; 0898; 0899
(2017/04/29)
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- Urea Derivatives of 2-Aryl-benzothiazol-5-amines: A New Class of Potential Drugs for Human African Trypanosomiasis
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A previous publication from this lab (Patrick, et al. Bioorg. Med. Chem. 2016, 24, 2451-2465) explored the antitrypanosomal activities of novel derivatives of 2-(2-benzamido)ethyl-4-phenylthiazole (1), which had been identified as a hit against Trypanosoma brucei, the causative agent of human African trypanosomiasis. While a number of these compounds, particularly the urea analogues, were quite potent, these molecules as a whole exhibited poor metabolic stability. The present work describes the synthesis of 65 new analogues arising from medicinal chemistry optimization at different sites on the molecule. The most promising compounds were the urea derivatives of 2-aryl-benzothiazol-5-amines. One such analogue, (S)-2-(3,4-difluorophenyl)-5-(3-fluoro-N-pyrrolidylamido)benzothiazole (57) was chosen for in vivo efficacy studies based upon in vitro activity, metabolic stability, and brain penetration. This compound attained 5/5 cures in murine models of both early and late stage human African trypanosomiasis, representing a new lead for the development of drugs to combat this neglected disease.
- Patrick, Donald A.,Gillespie, J. Robert,McQueen, Joshua,Hulverson, Matthew A.,Ranade, Ranae M.,Creason, Sharon A.,Herbst, Zackary M.,Gelb, Michael H.,Buckner, Frederick S.,Tidwell, Richard R.
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supporting information
p. 957 - 971
(2017/02/19)
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- A new synthesis of bicyclic N,O- and N,S-enaminals by the anionic cyclization of alk-4-ynals with amino alcohols and amino thiols
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A reaction of alk-4-ynals with aliphatic amino alcohols or 2-aminoethanethiol in the system DMSO - KOH gives bicyclic N,O- and N,S-enaminals: 6-methylidenehexahydro-2H-pyrrolo[2,1-b][1,3]oxazines, 5-methylidenehexahydropyrrolo[2,1-b]oxazoles, or 5-methyl-
- Gvozdev,Shavrin,Nefedov
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p. 409 - 415
(2015/02/02)
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- Synthesis of oxazolidin-2-ones and imidazolidin-2-ones directly from 1,3-diols or 3-amino alcohols using iodobenzene dichloride and sodium azide
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A general and efficient method for the synthesis of oxazolidin-2-ones and imidazolidin-2-ones directly from 1,3-diols and 3-amino alcohols has been developed using the same reagent combination of iodobenzene dichloride (PhICl2) and sodium azide (NaN3).
- He, Tian,Gao, Wen-Chao,Wang, Wei-Kun,Zhang, Chi
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supporting information
p. 1113 - 1118
(2014/04/03)
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- USE OF CONDENSED BENZO[B]THIAZINE DERIVATIVES AS CYTOPROTECTANTS
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The present invention relates to arylthiazine compounds, metabolites, N-oxides, amides, esters,pharmaceutically acceptable salts, hydrates and solvates thereof and their use as cytoprotectants in the treatment or prophylaxis of diseases or states, either acute or chronic, involving aberrant cellular lipid peroxidation in the central nervous system or in the periphery of the body. The present invention also relates to a method for their preparation and to pharmaceutical composition comprising as an active ingredient one or more of the aforementioned compounds.
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Page/Page column 64
(2014/12/12)
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- Rhodium-catalyzed asymmetric hydrogenation of olefins with PhthalaPhos, a new class of chiral supramolecular ligands
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A library of 19 binol-derived chiral monophosphites that contain a phthalic acid diamide group (Phthala- Phos) has been designed and synthesized in four steps. These new ligands were screened in the rhodium-catalyzed enantioselective hydrogenation of prochiral dehydroamino esters and enamides. Several members of the library showed excellent enantioselectivity with methyl 2-acetamido acrylate (6 ligands gave >97% ee), methyl (Z)-2- acetamido cinnamate (6 ligands gave >94% ee), and N-(1-phenylvinyl)acetamide (9 ligands gave >95% ee), whilst only a few representatives afforded high enantioselectivities for challenging and industrially relevant substrates N-(3,4-dihydronaphthalen-1- yl)-acetamide (96% ee in one case) and methyl (E)-2-(acetamidomethyl)-3- phenylacrylate (99% ee in one case). In most cases, the new ligands were more active and more stereoselective than their structurally related monodentate phosphites (which are devoid of functional groups that are capable of hydrogen-bonding interactions). Control experiments and kinetic studies were carried out that allowed us to demonstrate that hydrogen-bonding interactions involving the diamide group of the PhthalaPhos ligands strongly contribute to their outstanding catalytic properties. Computational studies carried out on a rhodium precatalyst and on a conceivable intermediate in the hydrogenation catalytic cycle shed some light on the role played by hydrogen bonding, which is likely to act in a substrate-orientation effect.
- Pignataro, Luca,Boghi, Michele,Civera, Monica,Carboni, Stefano,Piarulli, Umberto,Gennari, Cesare
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supporting information; experimental part
p. 1383 - 1400
(2012/03/27)
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- β-aryl nitrile construction via palladium-catalyzed decarboxylative benzylation of α-cyano aliphatic carboxylate salts
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The palladium-catalyzed decarboxylative benzylation of α-cyano aliphatic carboxylate salts with benzyl electrophiles was discovered. This reaction exhibits good functional group compatibility and proceeds under relatively mild conditions. A diverse range of quaternary, tertiary and secondary β-aryl nitriles can be conveniently prepared by this method. Copyright
- Shang, Rui,Huang, Zheng,Xiao, Xiao,Lu, Xi,Fu, Yao,Liu, Lei
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supporting information
p. 2465 - 2472,8
(2020/08/31)
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- PROCESS FOR PREPARING ALISKIREN AND ITS INTERMEDIATES
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The present application relates to a process for the preparation of aliskiren and its pharmaceutically acceptable salts. In particular, the present application relates to a process for the preparation of intermediates for aliskiren, and their conversion to aliskiren or its salts.
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Page/Page column 29
(2012/03/09)
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- BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS
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Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.
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Page/Page column 61
(2011/02/24)
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- TASK CHANNEL ANTAGONISTS
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This invention relates to TASK-1 and/or TASK-3 antagonists and/or their pharmaceutically acceptable salts, compositions and methods for treating and preventing disorders which are caused by activation or by an activated TASK-1 and/or TASK-3, and disorders
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Page/Page column 52
(2011/09/21)
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- PROCESS FOR THE PREPARATION OF (2S,4S,5S,7S)-N-(2-CARBAMYL-2- METHYLPROPYL)-5-AMINO-4-HYDROXY-2,7-DIISOPROPYL-8-[4-METHOXY-3-(3- METHOXYPROPOXY)PHENYL]-OCTANAMIDE HEMIFUMARATE AND ITS INTERMEDIATES THEREOF
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The present invention relates to a process for the preparation of (2S,4S,5S,7S)-N-(2- Carbamoyl-2-methylpropyl)-5-amino-4-hydroxy-2,7-diisopropyl-8-[4-methoxy-3-(3-methoxy propoxy )phenyl]-octanamide compound of formula- 1 and its pharmaceutically acceptable salts thereof. Further, relates to the processes for the preparation of (R)-4-(2-(halomethyl)-3- methylbutyl)-l-methoxy-2-(3-methoxypropoxy) benzene and (R)-2-(4-methoxy-3-(3-methoxy propoxy) benzyl)-3-methyIbutan-l-ol useful intermediates in the synthesis of compound of formula- 1.
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Page/Page column 63-64
(2011/12/14)
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- TASK CHANNEL ANTAGONISTS
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This invention relates to TASK-1 and/or TASK-3 antagonists and/or their pharmaceutically acceptable salts, compositions and methods for treating and preventing disorders which are caused by activation or by an activated TASK-1 and/or TASK-3, and disorders
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Page/Page column 52
(2011/09/30)
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- A PROCESS FOR DIMETHYLATION OF ACTIVE METHYLENE GROUPS
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The present invention discloses a process for dimethylation of active methylene groups. Specifically, the invention discloses aprocess for preparing3-amino-2,2- dimethylpropanamide. Compounds produced by the present dimethylation process such as 3-amino-2,2-dimethylpropanamide can be used as intermediates in the route of synthesis of therapeutic, prophylactic or diagnostic agent, for example aliskiren or cryptophycin. Particularly, the invention relates to embodiments further extending to processesfor preparing pharmaceutical dosage form comprising said therapeutic, prophylactic or diagnostic agents. More specifically, the invention relates to the use of compounds produced by the present dimethylation process for the manufacture of therapeutic, prophylactic or diagnostic agents or for the manufacture of pharmaceutical dosage forms comprising said therapeutic, prophylactic or diagnostic agents. The processes according to the present invention can be beneficially applied for the synthesis of various active pharmaceutical ingredients, such as aliskiren or crypthophycin.
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Page/Page column 29
(2010/11/03)
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- POLO-LIKE KINASE INHIBITORS
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Compounds of the following formula are provided for use with kinases, wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods and intermediates useful
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Page/Page column 207-208
(2009/06/27)
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- FUNGICIDAL HETEROCYCLIC COMPOUNDS
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A compound which can specifically or selectively expresses an antifungal activity with a broad spectrum, based on the functional mechanism of 1,6-β-glucan synthesis inhibition, is provided, and an antifungal agent which comprises such a compound, a salt thereof or a solvate thereof is provided. A compound represented by the following formula (I), a salt thereof or a solvate thereof.
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Page/Page column 60
(2010/11/24)
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- Synthetic intermediate for epothilone derivative and production method thereof
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The β-keto ester compound, β-hydroxy acid compound and acetonide form of a 1,3-diol derivative of the formulas (I), (V) and (VIII) wherein each symbol is as defined in the specification, are useful as a synthetic intermediate for an epothilone derivative being developed as a pharmaceutical agent having an antitumor activity.
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- Heterocyclic-substituted alkylamide acat inhibitors
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Pharmaceutically useful compounds having ACAT inhibitory activity of the formula wherein n is 0, 1, or 2, for X other than tetrazole and n = 2 then R2 = R3 = H; R1 is phenyl, substituted phenyl, naphthyl, substituted naphthyl, a heteroaromatic group or a hydrocarbon group having from one to 18 carbon atoms; R2 and R3 are hydrogen, halo, hydroxy, alkyl, alkenyl, cycloalkyl, phenyl, substituted phenyl, a heteroaryl, or form a spiroalkyl group; x is a 5-membered heteromonocyclic group containing at least one to four heteroatoms selected from the group consisting of isothiazole, oxazole, thiazole, imidazole, furan, thiophene, pyrrole, tetrazole, 1,2,3-triazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, 1,3,4-thiadiazole, 1,2,4-triazole, and 1,2,4-oxadiazole said heteromonocyclic group being unsubstituted or substituted at any available position along the ring,
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- Inhibitors of acyl-CoA:cholesterol O-acyltransferase. Synthesis and pharmacological activity of (±)-2-dodecyl-α-phenyl-N-(2,4,6- trimethoxyphenyl)-2H-tetrazole-5-acetamide and structurally related tetrazole amide derivatives
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A series of tetrazole amide derivatives of (±)-2-dodecyl-α-phenyl-N- (2,4,6-trimethoxyphenyl)-2H-tetrazole-5-acetamide (1) was prepared and evaluated for their ability to inhibit acyl-CoA: cholesterol O- acyltransferase (ACAT) in vitro and to lower plasma total cholesterol in vivo. For this series of compounds, our objective was to systematically replace substituents appended to the amide and tetrazole moieties of 1 with structurally diverse functionalities and assess the effect that these changes have on biological activity. The ensuing structure-activity relationship (SAR) studies identified aryl (7b) and heteroaryl (7f,g) replacements for 2,4,6-trimethoxyphenyl that potently inhibit liver microsomal and macrophage ACAT in vitro and exhibit good cholesterol lowering activity (56-66% decreases in plasma total cholesterol at 30 mg/kg), relative to 1, when compared in the acute rat model of hypercholesterolemia. Replacement of the α-phenyl moiety with electron-withdrawing substituents (13e-h), however, significantly reduced liver microsomal ACAT inhibitory activity (IC50 > 1 μM). This is in contrast to electron-donating substituents (13ij,m-q), which produce IC50 values ranging from 5 to 75 nM in the hepatic microsomal assay. For selected tetrazole amides (1, 7b, 13n,o), reversing the order of substituents appended to the 2- and 5-positions in the tetrazole ring (36a- d), in general, improved macrophage ACAT inhibitory activity and provided excellent cholesterol-lowering activity (ranging from 65% to 77% decreases in plasma total cholesterol at 30 mg/kg) in the acute rat screen. The most potent isomeric pair in this set of unsubstituted methylene derivatives (13n and 36a) caused adrenocortical cell degeneration in guinea pigs treated with these inhibitors. In contrast, adrenal glands taken from guinea pigs treated with the corresponding α-phenyl-substituted analogs (7b and 36c) were essentially unchanged compared to untreated controls. Subsequent evaluation of 7b and 36c in a rabbit bioassay showed that both compounds and/or their metabolites were present in plasma after oral dosing. Unlike 7b and 36c, compound 1 and related 2,4,6-trimethoxyanilides (13j, 30c,d) showed poor oral activity in the rabbit bioassay. Nevertheless, in cholesterol-fed rabbits, both systemically available (7b, 36c) and poorly absorbed inhibitors (1, 36d) were more effective in lowering plasma total cholesterol than the fatty acid amide CI-976.
- O'Brien,Sliskovic,Picard,Lee,Purchase II,Roth,White,Anderson,Mueller,Bocan,Bousley,Hamelehle,Homan,Lee,Krause,Reindel,Stanfield,Turluck
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p. 2354 - 2366
(2007/10/03)
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- Isoxazolyl-substituted alkyl amide ACAT inhibitors
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Pharmaceutically useful compounds having ACAT inhibitory activity of the formula STR1 wherein n is 0, 1, or 2, for X other than tetrazole and n=2 then R2 =R3 =H; R1 is phenyl, substituted phenyl, naphthyl, substituted naphthyl, a heteroaromatic group or a hydrocarbon group having from one to 18 carbon atoms; R2 and R3 are hydrogen, halo, hydroxy, alkyl, alkenyl, cycloalkyl, phenyl, substituted phenyl, a heteroaryl, or form a spiroalkyl group; X is a heteromonocyclic 5-membered ring containing one to four heteroatoms, said heteroatoms being nitrogen, oxygen or sulfur, and combination thereof; and R4 is a hydrocarbon group having from one to 20 carbon atoms are described as well as methods of their manufacture.
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- Electrochemical Carbon-skeleton Rearrangements catalysed by Hydrophobic Vitamin B12 immobilised in a Polymer-coated Electrode
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A glassy carbon electrode was coated with a polymer species derived from a hydrophobic vitamin B12 and Araldite CT-200, and the immobilised cobalt complex catalysed the electrochemical carbon-skeleton rearrangements of alkyl halides having electron-withdrawing groups.
- Murakami, Yukito,Hisaeda, Yoshio,Ozaki, Toshiaki,Matsuda, Yoshihisa
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p. 1094 - 1096
(2007/10/02)
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- Redox Behavior of Simple Vitamin B12 Model Complexes and Electrochemical Catalysis of Carbon-Skeleton Rearrangements
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Various cobalt complexes of 4,10-dipropyl-5,9-diazatrideca-4,9-diene-3,10-dione dioxime, (C2C3)(DOH)2pn, were prepared, and redox behavior of them was investigated by means of cyclic voltammetry; Co(II)/Co(I) redox potentials in the range of -0.69 through -0.7 V vs.Ag/AgCl.The monomethylated complex, which has a cobalt-carbon bond at one axial site of the nuclear cobalt, was disproportionated to the dimethylated complex, involving two cobalt-carbon bonds at both axial sites, and the CoI species by one-electron reduction.The dimethylated complex was inactive for electrochemical reduction, but transformed into the monomethylated complex via cleavage of a cobalt-carbon bond upon electrochemical oxidation.The electrolyses of 1-bromo-2,2-bis(ethoxycarbonyl)propane, 1-bromo-2-cyano-2-ethoxycarbonylpropane, and 2-acetyl-1-bromo-2-ethoxycarbonylpropane in the presence of IIIBr2> in N,N-dimethylformamide did not proceed in a divided cell at -2.0 vs.Ag/AgCl, since the corresponding dialkylated complexes, inactive for electrochemical reduction, were formed in the course of reaction.When imidazole was added to solutions for the electrolysis, the reaction proceeded efficiently by the trans effect arising from the coordinated axial base and the corresponding carbon-skeleton rearrangement products were obtained.On the other hand, the carbon-skeleton rearrangement proceeded in an undivided cell even in the absence of imidazole; the dialkylated complex was decomposed to give the monoalkylated complex and the reduction and rearrangement products by electrochemical ocxidation on the anode.
- Murakami, Yukito,Hisaeda, Yoshio,Fan, Sheng-Di,Matsuda, Yoshihisa
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p. 2219 - 2228
(2007/10/02)
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- Redox Behavior of Simple Vitamin B12 Model Complexes with Cobalt-Carbon Bonds and Catalytic Carbon-Skeleton Rearrangements
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The cobalt complex of 2,10-diethyl-3,9-dipropyl-1,4,8,11-tetraaazaundeca-1,3,8,10-tetraene-1,11-diol catalyzed electrolyses of alkyl halides with electron-withdrawing groups at the β-position to afford rearrangement products via oxidation of the corresponding dialkylated complexes as intermediates.
- Murakami, Yukito,Hisaeda, Yoshio,Fan, Sheng-Di,Matsuda, Yoshihisa
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p. 835 - 838
(2007/10/02)
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- Electrochemical Carbon-Skeleton Rearrangements as Catalyzed by Cyano-Coordinated Hydrophobic Vitamin B12
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Electrochemical carbon-skeleton rearrangements catalyzed by heptamethyl cobyrinate perchlorate proceeded more efficiently upon coordination of the cyanide ion to the central cobalt atom, and such enhanced catalysis was orihinated from facilitated formatio
- Murakami, Yukito,Hisaeda, Yoshio,Ozaki, Toshiaki,Matsuda, Yoshihisa
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p. 469 - 472
(2007/10/02)
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- Hydrophobic Vitamin B12. Part 6. Carbon-skeleton Rearrangement via Formation of Host-Guest Complexes derived from an 'Octopus Azaparacyclophane and hydrophobic Vitamin B12 Derivatives: a Novel Holoenzyme Model System
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The alkylation reactions of a hydrophobic vitamin B12 derivative with alkyl bromides in an 'octopus' azaparacyclophane having eight hydrocarbon chains have been investigated.Molecular discrimination has been shown to originate from electrostatic interaction between the octopus cyclophane and the alkyl bromides.Alkylation was enhanced by desolvation and proximity effects operating on the reacting species via formation of a ternary complex composed of the octopus cyclophane, the hydrophobic vitamin B12 derivative, and an alkyl halide.Carbon-skeleton rearrangement reactions of alkyl ligands bound to the hydrophobic vitamin B12 were found to be markedly favoured in the hydrophobic cavity provided by the octopus cyclophane, relative to the reactions in methanol and benzene, under anaerobic photolysis conditions at ordinary temperatures.The same reactions took place readily in solid benzene below 4 deg C under similar conditions.The central cobalt atom of the hydrophobic vitamin B12 participates in the rearrangement reaction via formation of a tight pair with an alkyl radical species.Non-enzymic rearrangement reactions have been shown here to proceed quite efficiently by employing a relevant apoenzyme model.
- Murakami, Yukito,Hisaeda, Yoshio,Kikuchi, Jun-ichi,Ohno, Teruhisa,Suzuki, Masashi,et al.
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p. 1237 - 1246
(2007/10/02)
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- Hydrophobic Vitamin B12. V. Electrochemical Carbon-Skeleton Rearrangement as Catalyzed by Hydrophobic Vitamin B12: Reaction Mechanisms and Migratory Aptitude of Functional Groups
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The carbon-skeleton rearrangements as catalyzed by heptamethyl cobyrinate perchlorate, 1ester>ClO4, were investigated under electrochemical conditions.The controlled-potential electrolysis of 2,2-bis(ethoxycarbonyl)-1-bromopropane, which is considered to be a model substrate for methylmalonyl-CoA mutase, was catalyzed by 1ester>ClO4 in N,N-dimethylformamide to give the rearrangement product, 1,2-bis(ethoxycarbonyl)propane, as a major one at -1.5 V vs.SCE in the presence of acetic acid and at potentials more cathodic than -1.8 V vs.SCE without acetic acid in the dark.The electrochemical carbon-skeleton rearrangement was postulated to proceed via formation of anionic intermediates.The electrolyses of 1-bromo-2-cyano-2-ethoxycarbonylpropane, 2-acetyl-1-bromo-2-ethoxycarbonylpropane, and 1-bromo-2-propane with 1ester>ClO4 also afforded the corresponding carbon-skeleton rearrangement products.The results indicated that substrates with two electron-withdrawing groups placed on the β-carbon atom with combination of one carboxylic ester and one of carboxylic ester, acetyl, and cyano moieties readily gave the corresponding rearrangement products which were derived from individual migration of the substituent groups.Substrates with only one of the electron-withdrawing groups, carboxylic ester, acetyl, and cyano, did not give any rearrangement product, but a substrate with one thioester group afforded the corresponding rearrangement product.The migratory aptitude of electron-withdrawing groups was found to decrease in the order: COSR>COR>COOR>CN.Both electronic character and steric bulkiness of the migrating groups are apparently reflected on this tendency, even though relative contributions of these effects are much dependent on the nature of β-substituents.
- Murakami, Yukito,Hisaeda, Yoshio,Ozaki, Toshiaki,Tashiro, Takako,Ohno, Teruhisa,et al.
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p. 311 - 324
(2007/10/02)
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- Enamines of 3,3-Dimethylazetidine
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In an improvement over previous procedures, 3,3-dimethylazetidine (3) has been synthesized in 26percent yield from ethyl cyanoacetate.Rates of formation for the enamines of 3 and of pyrrolidine with 2-methylcyclohexanone (1) and 1-tetralone (2) have been studied.The 5- to 10-fold rate increase observed for 3 is attributed to diminished steric hindrance relative to pyrrolidine.Compared to the enamines of pyrrolidine with 1 and 2, those of 3 methylate initially on nitrogen to ggreater degree and are less selective for monomethylation.The enamine formed between 1 and 3 exists at equilibrium as an 83.17 mixture of tri- and tetrasubstituted isomers, in which the less substituted isomer has its vinyl H 1H NMR peak at δ 4.10.These properties are compared to those of other enamines of 1, in which a predictive relationship had previously been suggested.
- Thompson, Hugh W.,Swistok, Joseph
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p. 4907 - 4911
(2007/10/02)
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