- Visible-Light-Induced Cycloaddition of α-Ketoacylsilanes with Imines: Facile Access to β-Lactams
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We report the synthesis of β-lactams from α-ketoacylsilanes and imines, which proceeds via a formal [2+2] photochemical cycloaddition with in situ generation of siloxyketene. This mild and operationally simple reaction proceeds in an atom-economic fashion with broad substrate scope, including aldimines, ketimines, hydrazones, and fused nitrogen heterocycles, affording a variety of important β-lactams with satisfactory diastereoselectivities in most cases. This reaction also features good functional-group tolerance, facile scalability and product diversification. Experimental and computational studies suggest that α-ketoacylsilanes can serve as photochemical precursors by engaging in a 1,3 silicon shift to the distal carbonyl group.
- Ye, Jian-Heng,Bellotti, Peter,Paulisch, Tiffany O.,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 13671 - 13676
(2021/05/11)
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- Direct C(sp3)-N Radical Coupling: Photocatalytic C-H Functionalization by Unconventional Intermolecular Hydrogen Atom Transfer to Aryl Radical
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An unconventional approach for intermolecular direct C(sp3)-N radical coupling has been developed by photocatalytic C(sp3)-H activation of simple alkyl substrates using O-benzoyl oximes. The selective photocatalytic energy-transfer-driven homolysis followed by decarboxylation generates the persistent iminyl radical and aryl radical, which would undergo an unprecedented intermolecular hydrogen atom abstraction from the alkyl substrate to provide the key C(sp3) radical. Selective radical-radical C-N cross-coupling furnishes imines which are valuable amine building blocks.
- Cho, Eun Jin,Hwang, Ho Seong,Kang, Jihee,Soni, Vineet Kumar
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- Catalytic asymmetric 1,3-dipolar cycloaddition of α-iminonitriles
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(Figure Presented) Improving the structural scope: A catalytic asymmetric 1,3-dipolar cycloaddition involving α-iminonitriles as azomethine precursors has been developed. In the presence of AgOAc/ Taniaphos as the catalyst system the reaction of α-iminonitriles with dimethyl fumarate and N-methyl maleimide affords 2-cyanopyrrolidines with good endo selectivity and enantioselectivity (68-≥99% ee; see scheme).
- Robles-Machín, Rocío,Alonso, Inés,Adrio, Javier,Carretero, Juan C.
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supporting information; experimental part
p. 5286 - 5291
(2010/10/01)
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- HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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Page/Page column 51-52
(2010/06/15)
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- DI-FLUORO CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S, and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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Page/Page column 38-39
(2009/10/30)
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- DI-FLUORO CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S, and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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Page/Page column 34
(2008/06/13)
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- HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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Page/Page column 49
(2008/06/13)
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- SULFONAMIDE COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds of formula ( I ) that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them. Wherein R3 is-alkylene-SO2NR5R6.
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Page/Page column 72-73
(2008/06/13)
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- PROCESSES AND INTERMEDIATES FOR PREPARING CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to a novel process for preparing certain cysteine protease inhibitors.
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Page/Page column 62-63
(2010/10/20)
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- SULFONYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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Page/Page column 58
(2010/11/24)
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- HALOALKYL CONTAINING COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is directed to pharmaceutical compositions comprising these compounds and processes for preparing them.
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Page/Page column 61-62
(2008/06/13)
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- SILINANE COMPOUNDS AS CYSTEINE PROTEASE INHIBITORS
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The present invention is directed to compounds that are inhibitors of cysteine proteases, in particular, cathepsins B, K, L, F, and S and are therefore useful in treating diseases mediated by these proteases. The present invention is also directed to pharmaceutical compositions comprising these compounds and processes for preparing them. The present invention is also directed to the use of these inhibitors in combination with a therapy that causes a deleterious immune response in patients receiving the therapy.
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Page/Page column 63
(2008/06/13)
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- The synthesis of alkyl aryl nitriles from N-(1-arylalkylidene)-cyanomethyl amines: Some mechanistic conclusions
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A mechanistic investigation of the rearrangement of N-(1-arylalkylidene)cyanomethylamines [1, ArC(=NCH2CN)R; R = alkyl, aryl] to alkyl aryl nitriles [2, ArCH(R)CN] in refluxing DMF in the presence of a base is reported. Under these conditions, p-phenyl substituted N-(1-arylethylidene)cyanomethylamines (Ar = p-BrC6H4, p-ClC6H4, p-CH3C6H4 and p-CH3OC6H4; R = CH3) follow the Hammett linear free-energy relationship, with a large positive p value (1.86), implying that electron-withdrawing substituents enhance the reaction rate by an initial deprotonation step. However, C-alkylated imines [Ph2C=NCH(R′)CN; R′ = Me, n-Bu] do not yield the corresponding nitriles [Ph2C(R′)CN], indicating the need for both methylene protons in order for the reaction to begin. Different mechanistic pathways are then discussed. A base-catalysed imine double bond isomerisation, considered plausible, is excluded, since N-alkylformimidoyl cyanides [ArCH(N=CHCN)R] interconvert quantitatively to imines 1 prior to the formation of nitriles 2. The photochemical activation of the reaction is also ruled out. The results of isotope labelling experiments, using 13C- and 15N-labelled N-(1-phenylethylidene)cyanomethylamines [PhC(=NCH2-13CN)CH3 and PhC(=15NCH2CN)CH3] are consistent with a mechanism based upon an intramolecular nucleophilic substitution reaction, since the cyano groups of the products 2 appear to come in preference from the methyleneiminic fragment (=NCH2-) of the reagents. The mechanism is proposed to proceed via an intermediate three-membered nitrogen heterocycle, generated by a nucleophilic intramolecular attack, which eliminates cyanide to afford the product nitrile.
- Perosa, Alvise,Selva, Maurizio,Tundo, Pietro
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p. 2485 - 2492
(2007/10/03)
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- Efficient synthesis of N-alkylformimidoyl cyanides
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N-Alkylformimidoyl cyanides (RRCHN=CHCN, 1) were obtained through a very efficient oxidation of N-alkylaminoacetonitriles (RRCHNHCH2CN, 2) by aq. NaOCl. The reaction was run under very mild and simple conditions and afforded products (as E/Z isomer mixtures; E/Z ratio of 70-99%) in short reaction times (30-180 min), and in good to excellent yields (67-97%).
- Perosa, Alvise,Selva, Maurizio,Tundo, Pietro
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p. 7573 - 7576
(2007/10/03)
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- Synthesis of alkylaryl-and diarylnitriles from ketones via N-(1- arylalkylidene)-cyanomethyl amines
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Alkylaryl- and diarylketones (Arcor; R= alkyl, aryl, 1) can be converted into nitriles [ArCH(CN)R, 2] containing an additional carbon atom through a base-promoted reaction of N-(1-arylalkylidene)-cyanomethyl amines [ArC(=NCH2CN)R, 3].
- Selva, Maurizio,Bomben, Andrea,Tundo, Pietro
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p. 1561 - 1569
(2007/10/03)
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- A simple one-pot synthesis of functionalized ketimines from ketones and amine hydrochloride salts
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Functionalized ketimines of the general formula RR'C (= NCH2Y) [R and R' = Ph, alkyl; Y = CN (1), CH2CI (2), COOMe (3)] have been prepared by the condensation of ketones with the corresponding primary amine hydrochloride salts [NH2CH2CN·HCl (4), NH2CH2CH2Cl·HCl (5) and NH2CH2COOMe·HCl (6), respectively]. The reported reaction proceeds mildly in a single step without the need of a previous isolation of the free amine from its salt. N,N-Dimethylformamide (DMF) is used as the solvent and TiCl4 as the drying agent.
- Selva,Tundo,Marques
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p. 369 - 378
(2007/10/02)
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- 1,1-Diphenyl-2-azaallenium Ions as Intermediates
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Under elimination of trimethylamine and formation of 1,1-diphenyl-2-azaallenium ion intermediates 2d from trimethylammonium iodide (5) on heating with sodium methanolate the N-(diphenylmethylene)methoxymethylamine (6) is obtained.With sodium methanethiolate the N-(diphenylmethylene)methylthiomethylamine (7), with sodium cyanide the acetonitrile (8) are formed.
- Boehme, Horst,Braun, Guenther,Ingendoh, Axel
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p. 717 - 719
(2007/10/02)
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- The Timing of the Proton-Transfer Process in Carbonyl Additions and Related Reactions. General-Acid-Catalyzed Hydrolysis of Imines and N-Acylimines of Benzophenone
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Observed general-acid-catalyzed hydrolysis of benzophenone imines, Ph2C=NR, or the kinetically equivalent general-base-catalyzed hydrolysis of the conjugate acids Ph2C=N+HR, corresponds mechanistically to general-base-catalyzed amine expulsion from the conjugate acid (T+) of the tetrhedral intermediate from water addition to Ph2C=NR.Broensted β values for this catalysis by carboxylate and cacodylate ions are 0.96 (for R = H), 0.93 (for R = C2H4CN), and 0.76 (for R = CH2CN).These results, combined with calculations that suggest that amine expulsion from the zwitterionic intermediate, T+/-, from ammonia is slower than diffusion processes involving T+/- and catalyst, are consistent with a mechanism in which a simple proton transfer process is not rate determining.Because of the stability of T+/- it is likely that catalysis in this system is "enforced" by the lifetime of this intermediate.We suggest that catalysis of these reactions is observed because hydrogen bonding of T+/- to the conjugate acid of the catalyst provides an energetic advantage by stabilizing both T+/- and the transition state for amine expulsion from this species.Hydrolysis of N-acyl benzophenone imines, Ph2C=NC(O)CH2X (X = H, OCH3, or Cl), involves a rapid, favorable equilibrium for addition of water across the C=N bond, followed by amide expulsion from the carbinolamide.The latter process, analogous to amine expulsion from carbinolamines, is subject to weak general acid catalysis with Broensted α values of 0.5-0.6.This catalysis probably corresponds mechanistically either to (1) bifunctional or "one-encounter" catalysis in which one or both of the proton-transfer processes is "concerted" with C-N cleavage, or (2) general base catalysis of the expulsion of the O-protonated amide from Ph2C(OH)N+HC(OH)CH2X.For uncatalyzed carbinolamide cleavage a cyclic transition state with intramolecular proton transfer to the acyl oxygen is suggested to explain the observed insensitivity to substituents, X, of amide expulsion from the neutral carbinolamides, Ph2C(OH)NHC(O)CH2X.
- Sayer, J. M.,Conlon, Patrick
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p. 3592 - 3600
(2007/10/02)
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