[3H]UR‐DE257: Development of a Tritium‐Labeled Squaramide‐Type Selective Histamine H2 Receptor Antagonist

A series of new piperidinomethylphenoxypropylamine‐type histamine H₂ receptor (H₂R) antagonists with different substituted “urea equivalents” was synthesized and characterized in functional in vitro assays. Based on these data as selection criteria, radiosynthesis of N‐[6‐(3,4‐dioxo‐2‐{3‐[3‐(piperidin‐1‐ylmethyl)phenoxy]propylamino}cyclobut‐1‐enylamino)hexyl]‐(2,3‐³H₂)propionic amide ([³H]UR‐DE257) was performed. The radioligand (specific activity: 63 Ci mmol^?1) had high affinity for human, rat, and guinea pig H₂R (hH₂R, Sf9 cells: K_d, saturation binding: 31 nM , kinetic studies: 20 nM ). UR‐DE257 revealed high H₂R selectivity on membranes of Sf9 cells, expressing the respective hH_xR subtype (K_i values: hH₁R: >10 000 nM , hH₂R: 28 nM , hH₃R: 3800 nM , hH₄R: >10 000 nM ). In spite of insurmountable antagonism, probably due to rebinding of [³H]UR‐DE257 to the H₂R (extended residence time), the title compound proved to be a valuable pharmacological tool for the determination of H₂R affinities in competition binding assays.     

Manganese‐Catalyzed ortho‐C−H Alkenylation of Aromatic N−H Imidates with Alkynes: Versatile Access to Mono‐Alkenylated Aromatic Nitriles

So far, the direct C−H alkenylation of aromatic nitriles with alkynes has not been achieved. Herein, we discribe the first manganese‐catalyzed C−H alkenylation of aromatic N−H imidates to access mono‐alkenylated aromatic nitriles. The reaction is accelerated by the presence of a catalytic amount of sodium pivalate. This protocol is also highlighted by the simple catalytic system, good compatibility of functional groups, and excellent mono‐/dialkenylation selectivity as well as E/Z stereoselectivity.

     

Ligand‐Free Copper‐Manganese Spinel Oxide‐Catalyzed Tandem One‐Pot C–H Amidation and N‐Arylation of Benzylamines: A Facile Access to 2‐Arylquinazolin‐4(3H)‐ones

An efficient ligand‐free copper‐manganese (Cu‐Mn) spinel oxide‐catalyzed direct tandem C−H oxygenation and N‐arylation of benzylamines has been developed. The method has been utilized for the synthesis of medicinally important 2‐arylquinazolin‐4(3H)‐ones. Salient features of this method include recyclable catalyst, no ligand, excellent product yields, shorter reaction times and a broad substrate scope.

     

Tritium‐Labeled N1‐[3‐(1H‐imidazol‐4‐yl)propyl]‐N2‐propionylguanidine ([3H]UR‐PI294), a High‐Affinity Histamine H3 and H4 Receptor Radioligand

Histamine mediates its various functions through four histamine receptor subtypes. The H₃ subtype is mainly found in the central nervous system, where it modulates the release of histamine and other neurotransmitters, whereas the H₄ subtype plays a crucial role in inflammatory and immunological processes. Herein, the synthesis and characterization of a conveniently accessible tritiated radioligand is reported that proved to be a versatile pharmacological probe.

     

Palladium‐Catalyzed Selective Aryl Ring C–H Activation of N‐Acyl‐2‐aminobiaryls: Efficient Access to Multiaryl‐Substituted Naphthalenes

Palladium‐catalyzed cycloaromatization of N‐acyl‐2‐aminobiaryls, through a sequence of ortho C−H bond activation/alkyne insertion/meta C−H bond activation/alkyne insertion, was developed. An efficient synthesis of multiaryl‐substituted naphthalenes, N‐[2‐(5,6,7,8‐tetraarylnaphthalen‐1‐yl)aryl]acetamides, was demonstrated using molecular oxygen as the sole oxidant. Furthermore, through Buchwald's synthetic protocol, two compounds were converted into corresponding fluorescent carbazoles in 30–40% yield by intramolecular C−N bond formation.

     

Copper‐Catalyzed Aryltrifluoromethylation of N‐Phenylcinnamamides: Access to Trifluoromethylated 3,4‐Dihydroquinolin‐2(1 H)‐ones

A method for copper‐catalyzed aryltrifluoromethylation of N‐phenylcinnamamides is reported. This method provides a straightforward route to a variety of CF₃‐containing 3,4‐dihydroquinolin‐2(1 H)‐ones with excellent regioselectivity and diastereoselectivity.

     

Copper‐Mediated Oxidative Radical Addition/Cyclization Cascade: Synthesis of Trifluoromethylated and Sulfonated Quinoline‐2,4(1H,3H)‐diones

A copper‐mediated oxidative radical addition/cyclization cascade of o‐cyanoarylacrylamides with sodium trifluoromethanesulfonate (Langlois’ reagent) has been achieved. The reaction proceeds through radical addition, cyclization, and imine hydrolysis, in which the cyclization was accomplished by an intramolecular addition of the carbon radical to the nitrile. This transformation exhibits a wide substrate scope and good functional group tolerance, thus providing a highly efficient and practical access to a variety of trifluoromethylated quinoline‐2,4(1H,3H)‐diones. Furthermore, using other sulfinic acid sodium salts as sulfonylating agents, sulfonated quinolinediones were also obtained through a similar radical cascade.

     

Nickel‐Catalyzed C–H Trifluoromethylation of Electron‐Rich Heteroarenes

The first example of a nickel‐catalyzed C–H trifluoromethylation of electron‐rich heteroarenes, including imidazopyridines, indoles and thiophenes, has been developed with the commercially available and relatively inexpensive industrial raw material iodotrifluoromethane (CF₃I) as the trifluoromethylating reagent. The synthetic potential of this method is demonstrated by its successful application to the direct trifluoromethylation of the biologically active molecules melatonin and zolmitriptan.

     

Copper(I)‐Catalysed Multicomponent Reaction: Straightforward Access to 5‐Hydroxy‐1H‐pyrrol‐2(5H)‐ones

A copper‐catalysed multicomponent coupling reaction between readily available (Z)‐3‐iodoacrylic acids, terminal alkynes, and primary amines was developed to smoothly access a small library of 5‐hydroxy‐1H‐pyrrol‐2(5H)‐ones in good yields. This practical and general process was applied to a short‐steps synthesis of the natural product pulchellalactam.

     

Enantioselective Copper‐Catalyzed Intramolecular N−H Bond Insertion: Synthesis of Chiral 2‐Carboxytetrahydroquinolines

The first highly enantioselective intramolecular N−H bond insertion was realized by using copper catalysts modified with chiral spirobisoxazoline ligands, which provides a novel strategy for the synthesis of chiral 2‐carboxytetrahydroquinolines. This reaction features fast reaction rate, high yield, high enantioselectivity, and mild reaction conditions.

     

Ionic polymer‐metal composites made from radiation grafted FEP‐g‐styrene‐SO3H membranes

Ionic polymer‐metal composites have been made from radiation grafted fluorinated ethylene propylene (FEP) membranes. Membranes have been synthesized by grafting of styrene on FEP films followed by sulfonation. These membranes were then used to fabricate IPMCs. Chemical plating of silver has been done to form the microelectrodes. Influence of degree of grafting on actuation, surface resistance, and tensile properties of the IPMC have been evaluated. It has been observed that on increasing the degree of grafting surface resistance, tensile strength, and elongation of IPMC decrease while degree of actuation and modulus increase. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Multi‐fuel scaled‐down autothermal pure H2 generator: Design and proof of concept

This article presents experimental results of an autothermal scaled‐down system for H₂ production. Pure atmospheric pressure H₂, separated in situ by Pd–Ag membranes, is produced by steam reforming (SR) of methane, ethanol, or glycerol. Oxidizing the SR effluents in a separate compartment supplies the heat. The oxidation feed is axially distributed to avoid hotspots. The 1.3 L system, comprises 100 cm² of membrane area, and generates H₂ flow rate equivalent to 0.15 kW at an efficiency of ～25%. This process leads to comparable performance when different fuels are used. A mathematical model, validated by the measurements, predicts that increasing the membrane area relative to the outer surface area will substantially increase the efficiency and power output. This design serves as proof of concept for on‐board pure H₂ generators, with flexible fuel sources, and holds a great promise to reduce the need for special H₂ transport and storage technologies for portable or stationary applications. © 2016 American Institute of Chemical Engineers AIChE J, 62: 2112–2125, 2016     

Copper‐Catalyzed Allenylation‐Isomerization Sequence of Penta‐1,4‐diyn‐3‐yl Acetates with P(O)H Compounds: Facile Synthesis of 1‐Phosphonyl 2,4‐Diynes

The copper‐catalyzed reaction of 5‐substituted penta‐1,4‐diyn‐3‐yl acetates with P(O)H compounds to efficiently give a new class of phosphonyl diynes is reported. The reaction may take place through a regioselective nucleophilic attack of phosphorus nucleophiles on Cu‐allenylidene intermediates to form allenyl intermediates followed by a rapid allene‐alkyne isomerization process. The synthetic utility of the obtained products is demonstrated.

     

Silver‐Catalyzed Intramolecular Cyclization of o‐(1‐Alkynyl)benzamides: Efficient Synthesis of (1H)‐Isochromen‐1‐imines

An efficient avenue for the facile and atom‐economic synthesis of (1H)‐isochromen‐1‐imines has been developed, and a broad spectrum of substrates can participate in the process effectively to produce the desired products in good yields. Significantly, this is the first report of the synthesis of (1H)‐isochromen‐1‐imines that involves a silver(I)‐catalyzed, regiocontrolled intramolecular addition of the carbonyl group of the amide moiety towards an alkyne.     

Copper‐Nitrene Triggered Annulation of α‐Acyl Cinnamides: Access to Isoxazol‐3(2H)‐ones

A facile and efficient one‐pot synthesis of isoxazol‐3(2H)‐ones has been developed starting from α‐acyl cinnamides and tosyliminophenyliodinane catalyzed by copper(II) acetate [Cu(OAc)₂] under very mild conditions involving a tandem aza‐Michael addition and intramolecular cyclization sequence.

     

Catalyst‐Free Domino Reaction of 1‐Acryloyl‐1‐N‐arylcarbamylcyclopropanes with Amines: One‐Pot Approach to 2,3,6,7‐Tetrahydro‐1H‐pyrrolo[3,2‐c]pyridin‐4(5H)‐ones

A facile one‐pot, catalyst‐free reaction has been developed for the synthesis of 2,3,6,7‐tetrahydro‐1H‐pyrrolo[3,2‐c]pyridin‐4(5H)‐ones from readily available 1‐acryloyl‐1‐N‐arylcarbamylcyclopropanes and amines using a domino ring‐opening/cyclization/aza‐addition sequence.

     

Functionalisation of lyocell. Part 2: Synthesis of 6‐p‐aminoanilino‐4‐p‐(β‐sulphatoethylsulphonyl)anilino‐1,3,5‐triazin‐2(1H)‐one†

A new water‐soluble monomeric agent for the aminisation of lyocell has been designed and synthesised. The agent, which contains a sulphatoethylsulphonyl group, an s‐triazinyl keto–enol tautomeric system and a primary aromatic amine was prepared in acidic media, in good yield from cyanuric chloride, p‐aminophenyl‐β‐sulphatoethylsulphone and p‐phenylenediamine, via a triazinyl betaine intermediate.