3893-23-0Relevant articles and documents
Efficient α-Alkylation of Arylacetonitriles with Secondary Alcohols Catalyzed by a Phosphine-Free Air-Stable Iridium(III) Complex
Panda, Surajit,Saha, Ratnakar,Sethi, Subrat,Ghosh, Rahul,Bagh, Bidraha
, p. 15610 - 15621 (2020/12/01)
A well-defined and readily available air-stable dimeric iridium(III) complex catalyzed α-alkylation of arylacetonitriles using secondary alcohols with the liberation of water as the only byproduct is reported. The α-alkylations were efficiently performed at 120 °C under solvent-free conditions with very low (0.1-0.01 mol %) catalyst loading. Various secondary alcohols including cyclic and acyclic alcohols and a wide variety of arylacetonitriles bearing different functional groups were converted into the corresponding α-alkylated products in good yields. Mechanistic study revealed that the reaction proceeds via alcohol activation by metal-ligand cooperation with the formation of reactive iridium-hydride species.
C-Alkylation of Various Carbonucleophiles with Secondary Alcohols under CoIII-Catalysis
Chakraborty, Priyanka,Garg, Nidhi,Manoury, Eric,Poli, Rinaldo,Sundararaju, Basker
, p. 8023 - 8031 (2020/08/21)
Oxindoles have been successfully α-alkylated under Cp*CoIII catalysis by a vast array of secondary alcohols, including cyclic, acyclic, symmetrical, and unsymmetrical, to produce C-alkylated oxindoles. This protocol was also extended to the α-alkylation of N,N-dimethyl barbituric acid and benzyl cyanides. The kinetic profile and other preliminary mechanistic investigations suggest a first-order reaction rate in oxindoles and catalysts. A plausible catalytic cycle is proposed on the basis of the kinetic profile, of other preliminary mechanistic investigations, and of previous mechanistic studies on similar transformations, whereas density functional theory calculations provide insight into the nature of the active species.
Hydride Reduction by a Sodium Hydride-Iodide Composite
Too, Pei Chui,Chan, Guo Hao,Tnay, Ya Lin,Hirao, Hajime,Chiba, Shunsuke
supporting information, p. 3719 - 3723 (2016/03/26)
Sodium hydride (NaH) is widely used as a Br?nsted base in chemical synthesis and reacts with various Br?nsted acids, whereas it rarely behaves as a reducing reagent through delivery of the hydride to polar π electrophiles. This study presents a series of reduction reactions of nitriles, amides, and imines as enabled by NaH in the presence of LiI or NaI. This remarkably simple protocol endows NaH with unprecedented and unique hydride-donor chemical reactivity.
Enantioselective Rhodium-Catalyzed Allylic Alkylation of Prochiral α,α-Disubstituted Aldehyde Enolates for the Construction of Acyclic Quaternary Stereogenic Centers
Wright, Timothy B.,Evans, P. Andrew
supporting information, p. 15303 - 15306 (2016/12/09)
A highly enantioselective rhodium-catalyzed allylic alkylation of prochiral α,α-disubstituted aldehyde enolates with allyl benzoate is described. This protocol provides a novel approach for the synthesis of acyclic quaternary carbon stereogenic centers and it represents the first example of the direct enantioselective alkylation of an aldehyde enolate per se. The versatility of the α-quaternary aldehyde products is demonstrated through their conversion to a variety of useful motifs applicable to target-directed synthesis. Finally, mechanistic studies indicate that high levels of asymmetric induction are achieved from a mixture of prochiral (E)- and (Z)-enolates, which provides an exciting development for this type of transformation.
Nitrile synthesis through catalyzed cascades involving acid-nitrile exchange
Cartigny, Damien,Dos Santos, Aurelie,El Kaim, Laurent,Grimaud, Laurence,Jacquot, Roland,Marion, Philippe
, p. 1802 - 1806 (2014/07/08)
Irreversible acid-nitrile exchange reactions using both glutaronitrile and (phenylsulfonyl)acetonitrile may be catalyzed by Lewis acids. Whereas a cyclization towards imides displaces the equilibria in the reaction with dinitriles, a decarboxylation step is involved when using the (phenylsulfonyl)acetonitrile. Georg Thieme Verlag Stuttgart New York.
Synthesis of α-aryl esters and nitriles: Deaminative coupling of α-aminoesters and α-aminoacetonitriles with arylboronic acids
Wu, Guojiao,Deng, Yifan,Wu, Chaoqiang,Zhang, Yan,Wang, Jianbo
supporting information, p. 10510 - 10514 (2016/02/18)
Transition-metal-free synthesis of α-aryl esters and nitriles using arylboronic acids with α-aminoesters and α-aminoacetonitriles, respectively, as the starting materials has been developed. The reaction represents a rare case of converting C(sp3)-N bonds into C(sp3)-C(sp2) bonds. The reaction conditions are mild, demonstrate good functional-group tolerance, and can be scaled up. Touch base: A transition-metal-free protocol for the synthesis of α-aryl esters and nitriles by deaminative coupling is presented. Strong bases and transition-metal catalysts are not needed. The new synthetic method uses readily available starting materials and demonstrates wide substrate scope.
MUSCARINIC RECEPTOR ANTAGONISTS
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Page/Page column 28, (2008/12/04)
The present invention relates to muscarinic receptor antagonists, which are useful, among other uses, for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through muscarinic receptors. The invention also relates to the process for the preparation of disclosed compounds, pharmaceutical compositions containing the disclosed compounds, and the methods for treating diseases mediated through muscarinic receptors. Also provided herein are pharmaceutical compositions comprising one or more muscarinic receptor antagonists and at least one or more therapeutic agent selected from histamine antagonists, corticosteroids, beta agonists, leukotriene antagonists, EGFR kinase inhibitors, PAF antagonists, 5-lipoxygenase inhibitors, chemokine inhibitors, PDE-4 inhibitors or p38 MAP Kinase inhibitors.
Phase transfer alkylation of arylacetonitriles revisited
Barbasiewicz, Micha?,Marciniak, Karolina,Fedoryński, Micha?
, p. 3871 - 3874 (2007/10/03)
Phase transfer alkylations of phenylacetonitrile derivatives carried out in the presence of 60-75% aqueous KOH, instead of the typical 50% NaOH, provide substantial improvements in the overall yields and purity of products. Reactions with simple secondary alkyl halides, as well as cycloalkylations with 1,2- and 1,3-dihaloalkanes proceed with good yields. Increasing the concentration of base diminishes the formation of by-products from competitive β-elimination processes.
Phenyl-substituted normethadones: Synthesis and pharmacology
Mbela,Poupaert,Cumps,Moussebois,Haemers,Borloo,Dumont
, p. 237 - 242 (2007/10/02)
Phenyl-substituted normethadone derivatives were synthesized and their affinity (IC50) for opioid receptors was determined by displacement of the specific binding sites of [3H]sufentanyl on rat brain preparations. Substitution resulted in a decrease of affinity in-vitro. These results suggest that normethadone-like compounds may interact with the P subsite of the μ-opioid receptor and that the P subsite has a well-defined cavity shape of stringent dimensions.
Synthesis and aromatase inhibition of 3-cycloalkyl-substituted 3-(4- aminophenyl)piperidine-2,6-diones
Hartmann,Batzl,Pongratz,Mannschreck
, p. 2210 - 2214 (2007/10/02)
The synthesis of 3-cycloalkyl-substituted 3-(4-aminophenyl)piperidine-2,6- diones is described [cyclopentyl (1), cyclohexyl (2)]. The enantiomers of 2 were separated either by using HPLC on optically active sorbent or by crystallization of the brucine salt of the phthalamic acid of 2. The absolute configuration of the (+)- and (-)-enantiomers of 2 were assigned as S and R, respectively, by comparing the CD spectra to those of the enantiomers of aminoglutethimide (AG, 3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione). The compounds were tested in vitro for inhibition of human placental aromatase, the cytochrome P450-dependent enzyme which is responsible for the conversion of androgens to estrogens. Compounds 1 and 2 inhibited aromatase by 50% at 1.2 and 0.3 μM, respectively (IC50 AG = 37 μM). According to the findings with AG, the (+)-enantiomer of 2 was responsible for the inhibitory activity, being a 240-fold more potent aromatase inhibitor in vitro than racemic AG. On the other hand, (+)-2 displayed a strongly reduced inhibition of desmolase (cholesterol side-chain cleavage enzyme) compared to AG (relative activity = 0.3). Thus (+)-2 is of interest as a potential drug for the treatment of estrogen-dependent diseases, e.g. mammary tumors.
