61516-73-2Relevant academic research and scientific papers
Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones
De Koning, Charles B.,Klintworth, Robin,Michael, Joseph P.,Morgans, Garreth L.,Scalzullo, Stefania M.,Van Otterlo, Willem A. L.0000-0002-3300-6463
supporting information, p. 2543 - 2552 (2021/11/30)
A wide range of N-(ethoxycarbonylmethyl)enaminones, prepared by the Eschenmoser sulfide contraction between N-(ethoxycarbonylmethyl) pyrrolidine-2-thione and various bromomethyl aryl and heteroaryl ketones, underwent cyclization in the presence of silica gel to give ethyl 6-(hetero)aryl-2,3-dihydro-1H-pyrrolizine-5-carboxylates within minutes upon microwave heating in xylene at 150 °C. Instead of functioning as a nucleophile, the enaminone acted as an electrophile at its carbonyl group during the cyclization. Yields of the bicyclic products were generally above 75%. The analogous microwave-assisted reaction to produce ethyl 2-aryl- 5,6,7,8-tetrahydroindolizine-3-carboxylates from (E)-ethyl 2-[2-(2-oxo-2-arylethylidene)piperidin-1-yl]acetates failed in nonpolar solvents, but occurred in ethanol at lower temperature and microwave power, although requiring much longer time. A possible mechanism for the cyclization is presented, and further functionalization of the newly created pyrrole ring in the dihydropyrrolizine core is described.
COMPOUNDS USEFUL IN HIV THERAPY
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Page/Page column 41, (2019/05/22)
The invention relates to compounds of Formulas (I), (II) and (III) salts thereof, pharmaceutical compositions thereof, as well as methods of treating, curing or preventing HIV in subjects.
Ugi Four-Center Three-Component Reaction as a Direct Approach to Racetams
Cioc, R?zvan C.,Schaepkens van Riempst, Lola,Schuckman, Peter,Ruijter, Eelco,Orru, Romano V. A.
, p. 1664 - 1674 (2017/03/21)
We report the synthesis of racetams, a diverse class of small molecule drugs, by means of the Ugi four-center three-component reaction (U4C-3CR). For the first time, γ-aminobutyric acid is employed as bifunctional input in the Ugi reaction. This protocol is simple, general, and allows one-pot access to a range of drugs and bioactive small molecules.
A method for the preparation of pyrrolidine alkone second grade ester (by machine translation)
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Paragraph 0033; 0034; 0035, (2016/12/12)
The invention discloses a method for the preparation of pyrrolidine alkone second grade acid ester, the method comprising the following steps: a) the 4-amino ding Xianlu alkaliferous with halogenated acetic acid ester in the non-polar solvent in the condensation reaction, to obtain amido acetate; b) the amino-acetic acid ester in the alkaliferous non-proton polar solvents in the ring reaction lactan, pyrrolidine alkone second grade acid ester is obtained; as shown in the following synthetic route: Wherein: X chlorine, bromine or iodine; R is phenyl, benzyl or C1-C3 straight chain paraffin base. Experiment proves that: the method of the invention has the advantages of simple operation, mild reaction conditions, the low requirements for the equipment, the raw materials used are cheap and easily obtained, low production cost, easy large-scale production, and the like, in accordance with industrial preparation of pyrrolidine alkone second grade ester production requirement, has industrial application value. (by machine translation)
Structure dependence in the solvolysis kinetics of amino acid esters
Haseltine, John,Runyon, Jason W.
experimental part, p. 3280 - 3283 (2010/07/18)
To better understand acyl transfer reactions of oligopeptides, seventeen N-acyl amino acid esters were solvolyzed in mildly basic methanol-d4. All show pseudo-first-order kinetics by 1H NMR. The rate constant varies up to 400-fold with the identity of the amino acid and up to 6200-fold with the identity of the N-acyl group. The impact of the N-acyl group on the rate constant is discussed in terms of crowding, amide conformation, and amide C{double bond, long}O bond character.
Triton B-mediated mild, convenient, and efficient method for the selective alkylation of cyclic secondary amines and thiols
Meshram,Reddy, B. Chennakesava,Goud, P. Ramesh
experimental part, p. 2297 - 2303 (2009/12/01)
Alkylation of cyclic secondary amines, thiols, and pyridazinones has been demonstrated with alkyl halides using Triton B as base and reaction medium.
Synthesis and anticonvulsant activity of some 1-substituted-2- oxopyrrolidine derivatives, II
Al-Obaid, Abdulrahman M.,El-Subbagh, Hussein I.,Al-Shabanah, Othman A.,Elmazar, Mohamed M.
, p. 696 - 721 (2007/10/03)
In the present study, as an attempt to locate new antiepileptic agent(s) with less side effects as well as toxicity, a new series of N-substituted-2- oxopyrrolidine derivatives was synthesized as GABA prodrugs and evaluated for their anticonvulsant activity adopting various screening models. N(4- Fluorobenzyl)-2-(2-oxopyrrolidin-1-yl)acetamide (14) proved to possess a potent broad spectrum anticonvulsant activity with wide safety margin, compared with valproic acid. Compound 14 is more potent (ED50 = 0.43 vs 0.71 mmol/kg for valproate) and has a higher protective index against convulsions (PI = 2.81 vs 1.4-2.36 for valproate). Compound 14 with doses up to 0.5 and 1.0 g/kg, i.p., did not produce mortality within 24 h after administration. N-(4-Methoxybenzyl)-2-(2-oxopyrrolidin-1-yl)acetamide (15), N-(phenylethyl)-2-(2-oxopyrrolidin-1-yl)acetamide (16) and N-[2-(4- fluorophenyl)ethyl]-2-(2-oxopyrrolidin-1-yl)acetamide (17) are also among the potent derivatives found in this investigation. Compounds 14-17, however, have lipophilicity Log (p) values of 0.12-0.68 which is lower than that of valproate. The finding that compounds 14-16 protect against bicuculline- induced convulsions, confirms the rationale behind the design of the present series of compounds as GABA prodrugs.
β-Hydroxypiperidinecarboxylates: Additions to the chiral pool from bakers' yeast reductions of β-ketopiperidinecarboxylates
Knight, David W.,Lewis, Neil,Share, Andrew C.,Haigh, David
, p. 3673 - 3683 (2007/10/03)
Reduction of the piperidine keto esters 16-19 using fermenting bakers' yeast provides high yields of the corresponding hydroxy esters 20, 26, 32 and 37 respectively, exclusively as the cis-diastereoisomers and with good levels (≥80%) of enantiomeric enrichment. The relative stereochemistries of the products were deduced from NMR data while the absolute configurations were determined by degradation to known piperidinemethanol derivatives or, in the case of hydroxy ester 37, by homologation to (R)-3-quinuclidinol 41b.
Lactam & amide acetals XXI. Use of pyroglutamic acid and proline in chiral synthesis of conformationally constrained piperazinones
Jain, Sanjay,Sujatha,Rama Krishna,Roy, Raja,Singh, Jujhar,Anand, Nitya
, p. 4985 - 4998 (2007/10/02)
Making use of amide activation chiral synthesis of (+)-(1S,5R)- and (-)-(1R,5S)-3,8-diazabicyclo [3.2.1]octan-2-ones (1 and 2) has been achieved from L- and D-pyroglutamates, and of (-)-(2R,6S)-, (-)-(2S,6S)-, (+)-(2s,6R)- and (+)-(2R,6R)-2-methyl-1,4-diazabicyclo[4.3.0]nonan-5-ones (3a,3b,4a and 4b) from L & D-proline methyl esters respectively. The key step of the synthesis involves a stereo-selective catalytic hydrogenation, accompanied with spontaneous cyclisation, o the nitroenamines 11, 14, 17 and 19. While this reaction was stereospecific in the case of pyro-Glu derived nitroenamines ( 11 and 14), with N-acetyl-proline derived nitroenamines (17 and 19) both 2R and 2S diastereoisomers were obtained with 40% d.e. of the diastereomer with 2-CH3 oriented cis to the 6-H. The piperazinones 1 and 2 on treatment with methanolic HCl at room temperature yielded the corresponding optically pure 5-aminomethylprolines 12 and 15 respectively.
