2901-29-3Relevant academic research and scientific papers
One-Pot Reaction of Carboxylic Acids and Ynol Ethers for the Synthesis of β-Keto Esters
Zeng, Linwei,Lai, Zhencheng,Cui, Sunliang
, p. 14834 - 14841 (2018/12/14)
An one-pot reaction of carboxylic acids and ynol ethers for the synthesis of β-keto esters has been developed. Under promotion of Ag2O, various carboxylic acids and ynol ethers could transform to α-acyloxy enol esters, which undergo a following DMAP-catalyzed rearrangement to deliver β-keto esters rapidly. This method provides a direct approach to β-keto esters from carboxylic acids without any preactivation. The protocol features mild reaction conditions, broad substrate scope, and the products could be transformed to an array of compounds.
One-pot tandem Hurtley-retro-Claisen-cyclisation reactions in the synthesis of 3-substituted analogues of 5-aminoisoquinolin-1-one (5-AIQ), a water-soluble inhibitor of PARPs
Woon, Esther C.Y.,Sunderland, Peter T.,Paine, Helen A.,Lloyd, Matthew D.,Thompson, Andrew S.,Threadgill, Michael D.
, p. 5218 - 5227 (2013/09/02)
Poly(ADP-ribose)polymerase-1 (PARP-1) is an important target for drug design for several therapeutic applications. 5-Aminoisoquinolin-1-one (5-AIQ) is a highly water-soluble lead compound; synthetic routes to 3-substituted analogues were explored. Tandem Hurtley coupling of β-diketones with 2-bromo-3-nitrobenzoic acid, retro-Claisen acyl cleavage and cyclisation gave the corresponding 3-substituted 5-nitroisocoumarins. Treatment with ammonia at high temperature and reduction with tin(II) chloride gave eleven target 3-substituted 5-AIQs, which were all soluble in water (>1% w/v) as their HCl salts. Most were more potent than 5-AIQ as inhibitors of PARP-1 and of PARP-2 in vitro, the most active being 5-amino-3-methylisoquinolin-1-one (PARP-1: IC 50 = 0.23 μM vs IC50 = 1.6 μM for 5-AIQ). Some rationalisation of the SAR was achieved through molecular modelling.
Studies with 3-Oxoalkanenitriles: Synthesis of new Pyrazolopyrimidines and Pyrazolotriazines and Reactivity of 4-Phenyl-3-oxobutanenitrilke Derivatives
Khalik, Mervat Mohammed Abdel
, p. 1377 - 1389 (2007/10/03)
4-Phenyl-3-oxobutanenitrile 6 could be synthesized via reacting ethyl phenylacetate with acetonitrile in presence of sodium hydride.Although this product could not be isolated in pure form, it was identified via isolating its 2-phenylhydrazone derivative 4 and its dimethylaminomethylidene derivative 5.Both the hydrazone and the dimethylaminomethylidene derivatives proved versatile starting materials for synthesis of a variety of polyfunctionally substituted heterocycles.The reaction of 4 with hydrazine hydrate afforded 3-benzyl-4- phenylazo-1H-pyrazolo-5-amine 1.Compound 5 reacted with 3-amino-5- methylpyrazole to yield 5-benzyl-2-methylpyrazolopyrimidine-6-carbonitrile 2.The reaction of 4 with a variety of reagents enabled synthesis of a pyridazinone 10 and a benzocinnoline derivative 14.Compound 1 could be converted into pyrazolopyrimidine derivatives 17,19 by reaction with bifunctional electrophiles.In addition, compound 1 was diazotized then coupled with active methylene, β-naphthol or resorcinol affording phenylazopyrazolotriazine derivatives 22-24.
Ester Homologation Revisited: A Reliable, Higher Yielding and Better Understood Procedure
Kowalski, Conrad J.,Reddy, Rajarathnam E.
, p. 7194 - 7208 (2007/10/02)
Enolate anions 3 and 6, prepared via enolization of α-bromo and dibromo ketones 4 and 5 were converted in high yield to ynolate anions 10 by respective addition of lithium tetramethylpiperidide (to effect deprotonation, 3 --> 7) or butyllithium (to effect metal-halogen exchange, 6 --> 7).Mixtures of such enolates were also obtainable from esters 1 on a large-scale (25 mmol) via in situ formation and addition of lithiodibromomethane (from methylene bromide and lithium tetramethylpiperidide), followed by treatment of the resulting adducts with lithiumhexamethyldisilazide to ensure complete enolization.Addition of sec-butyllithium and n-butyllithium to effect ynolate anion formation, followed by quenching of the reaction mixtures into acidic ethanol, reproducibly afforded homologated esters 8 in 67-90percent yield.Demonstrated for ethyl esters 1 having the carbethoxy moiety attached to primary, secondary, tertiary, aryl, and alkenyl groups, this general procedure provides a convenient, large-scale alternative to the classical Arndt-Eistert sequence.
ELECTRON TRANSFER REACTIONS OF ALIPHATIC ESTERS TO THE CORRESPONDING ALIPHATIC KETONES BY LITHIUM 4,4'-DI-T-BUTYLBIPHENYL RADICAL ANION
Karaman, Rafik,Fry, James L.
, p. 4935 - 4938 (2007/10/02)
Sonication of some representative aliphatic esters with lithium in the presence of catalytic amounts of 4,4'-di-t-butylbiphenyl (DBB) in dry THF under N2 afforded the corresponding aliphatic ketones in good yields.Monitoring studies by GC/MS and 1H-NMR spectroscopy after quenching indicate the intermediacy of the corresponding β-ketoesters.
Pyrazole Chemistry I: Efficient Syntheses of Aryl or Benzyl 4-Pyrazolyl Ketones and Carbinols
Heinisch, Gottfried,Holzer, Wolfgang,Huber, Thierry
, p. 1267 - 1272 (2007/10/02)
Dilithiation of 4-bromopyrazole followed by reaction with appropriate electrophiles provides an improved access to 4-benzoylpyrazole (3) and the corresponding alcohol 4a.In a similar manner the homologous compounds 5 and 7 are conveniently available.
