59223-74-4

Upstream product

• 332-42-3 (2-bromoethyl)-4-fluorobenzene 
• 105-53-3 diethyl malonate 
• 790-53-4 diethyl 2-(4-fluorobenzylidene)malonate 
• 459-46-1 4-Fluorobenzyl bromide 
• 352-11-4 1-chloromethyl-4-fluorobenzene 
• 996-82-7 sodium diethylmalonate 

Downstream Products

• 502769-42-8 2-[2-(dimethylamino)ethyl]-2-(4-fluorobenzyl)malonic acid diethyl ester 
• 1282061-23-7 C₁₉H₁₈FNO 
• 78573-76-9 2-(4-fluorobenzyl)malonic acid 
• 191930-41-3 (±)-ethyl 2-amino-3-(4-fluorophenyl)propanoate 
• 1353886-54-0 ethyl 3-(4-fluorophenyl)-2-(hydroxyimino)propanoate 
• 287212-45-7 monoethyl (4-fluorobenzyl)malonate 
• 1597430-55-1 C₁₈H₂₂FN₃O₆ 

Relevant academic research and scientific papers

Ball-Milling-Enabled Reactivity of Manganese Metal**

Efforts to generate organomanganese reagents under ball-milling conditions have led to the serendipitous discovery that manganese metal can mediate the reductive dimerization of arylidene malonates. The newly uncovered process has been optimized and its mechanism explored using CV measurements, radical trapping experiments, EPR spectroscopy, and solution control reactions. This unique reactivity can also be translated to solution whereupon pre-milling of the manganese is required.

COMPOUNDS, SALTS THEREOF AND METHODS FOR TREATMENT OF DISEASES

The present disclosure relates to compounds according to Formula (I), treating diseases.

Anodic benzylic C(sp3)-H amination: Unified access to pyrrolidines and piperidines

An electrochemical aliphatic C-H amination strategy was developed to access the important heterocyclic motifs of pyrrolidines and piperidines within a uniform reaction protocol. The mechanism of this unprecedented C-H amination strategy involves anodic C-H activation to generate a benzylic cation, which is efficiently trapped by a nitrogen nucleophile. The applicability of the process is demonstrated for 40 examples comprising both 5- and 6-membered ring formations.

Biocatalytic Desymmetrization of Prochiral 3-Aryl and 3-Arylmethyl Glutaramides: Different Remote Substituent Effect on Catalytic Efficiency and Enantioselectivity

Catalyzed by an amidase-containing Rhodococcus erythropolis AJ270 microbial whole cell catalyst in neutral phosphate buffer at 30 °C, desymmetric hydrolysis of a series of prochiral 3-aryl and 3-arylmethylglutaramides efficiently afforded 3-substituted glutaric acid monoamides in up to 95% yield and >99.5% ee. Even far away from the reaction site, the substituents on the aryl still have a significant effect on the catalytic activity and enantioselectivity and different remote substituent effect was observed for the two types of substrates. The synthetic application of biocatalytic desymmetrization was demonstrated by the facile transformation of the obtained enantiopure (R)-3-substituted 4-carbamoylbutanoic acid products to chiral dihydroquinolinone and δ-lactone compounds. (Figure presented.).

Synthesis and insecticidal activity of mesoionic pyrido[1,2-α]pyrimidinone derivatives containing a neonicotinoid moiety

Mesoionic pyrido[1,2-α]pyrimidinone derivatives containing a neonicotinoid moiety were designed, synthesized, and evaluated for their insecticidal activity. Some of the title compounds showed remarkable insecticidal properties against Aphis craccivora. Compound I13 exhibited satisfactory insecticidal activity against A. craccivora. Meanwhile, label-free proteomics analysis of compound I13 treatment identified a total of 821 proteins. Of these, 35 proteins were up-regulated, whereas 108 proteins were down-regulated. Differential expressions of these proteins reflected a change in cellular structure and metabolism.

4-alkyloxyimino derivatives of uridine-5′-triphosphate: Distal modification of potent agonists as a strategy for molecular probes of P2Y 2, P2Y4, and P2Y6 receptors

Extended N4-(3-arylpropyl)oxy derivatives of uridine-5′-triphosphate were synthesized and potently stimulated phospholipase C stimulation in astrocytoma cells expressing G protein-coupled human (h) P2Y receptors (P2YRs) activated by UTP (P2Y2/4R) or UDP (P2Y6R). The potent P2Y4R-selective N4-(3- phenylpropyl)oxy agonist was phenyl ring-substituted or replaced with terminal heterocyclic or naphthyl rings with retention of P2YR potency. This broad tolerance for steric bulk in a distal region was not observed for dinucleoside tetraphosphate agonists with both nucleobases substituted. The potent N 4-(3-(4-methoxyphenyl)-propyl)oxy analogue 19 (EC50: P2Y2R, 47 nM; P2Y4R, 23 nM) was functionalized for chain extension using click tethering of fluorophores as prosthetic groups. The BODIPY 630/650 conjugate 28 (MRS4162) exhibited EC50 values of 70, 66, and 23 nM at the hP2Y2/4/6Rs, respectively, and specifically labeled cells expressing the P2Y6R. Thus, an extended N4-(3- arylpropyl)oxy group accessed a structurally permissive region on three G q-coupled P2YRs, and potency and selectivity were modulated by distal structural changes. This freedom of substitution was utilized to design of a pan-agonist fluorescent probe of a subset of uracil nucleotide-activated hP2YRs.

Tuning the lewis acidity of boranes in frustrated lewis pair chemistry: Implications for the hydrogenation of electron-poor alkenes

An analysis of the metal-free reduction of electron deficient olefins by frustrated Lewis pairs indicates that the rate-determining step might be either the heterolytic cleavage of H2 to form an -onium borohydride salt, or the subsequent transfer of the hydride moiety to the substrate following a Michael-type addition reaction. While the use of strong Lewis acids such as B(C6F5)3 facilitates the first of these processes, hydride transfer to the olefin should be contrarily favoured by the use of weak Lewis acids which, for this very same reason, might be unable to promote the prior H2 split. After systematic testing of several boranes of different Lewis acidity (assessed by using the Childs' method) and steric demand, an optimal situation that employs tris(2,4,6-trifluorophenyl) borane was reached. Mixtures of this borane with 1,4-diazabicyclo[2.2.2]octane (DABCO) exhibited excellent catalytic activity for the hydrogenation of alkylidene malonates. In fact, this transformation could be achieved under milder conditions than those we reported previously. Moreover, the reaction scope could be expanded to other electron deficient olefins containing esters, sulfones or nitro functionalities as electron-withdrawing substituents.

Metal-free hydrogenation of electron-poor allenes and alkenes

The poorer, the better: A metal-free catalytic procedure for the reduction of electron-poor allenes and alkenes has been developed. The method employs a frustrated Lewis pair based catalyst. 1,4-Diazabicyclo[2.2.2]octane (DABCO)/B(C6F5)3 was shown to be the best combination in optimization studies. Copyright

Pd(II)-catalyzed intramolecular amidoarylation of alkenes with molecular oxygen as sole oxidant

Stereoselective palladium-catalyzed synthesis of structurally versatile indoline derivatives, using molecular oxygen as the sole oxidant, is described. New C-N and C-C bonds form across an alkene in an intramolecular manner. The C-N bond-forming step proceeds via a syn-amidopalladation pathway. The moderate kinetic isotope effects (intramolecular KIE = 3.56) suggest that electrophilic aromatic substitution occurs in the arylation step.

Structure-activity relationships of dimethindene derivatives as new M2-selective muscarinic receptor antagonists

A series of 2,3-disubstituted indenes, which are analogues of the widely used histamine H1 receptor antagonist dimethindene, have been synthesized and studied as muscarinic and histamine receptor antagonists. The affinities of these compounds for the five human muscarinic receptor subtypes (M1-M5) and for human histamine H1 receptors were determined in radioligand binding studies using membranes from transfected Chinese hamster ovary (CHO) cells and [3H]N-methylscopolamine ([3H]NMS). The results demonstrate that the diisopropyl analogue 19 has a similar high affinity as (S)-dimethindene at M2 receptors ((S)-dimethindene: pKi = 7.52; (-)-19: pKi = 7.37) with an improved selectivity pattern ((S)-dimethindene: M2/M1 = 6-fold, M2/M3 = 5-fold, M2/M4 = 10-fold, M2/M5 = 25-fold; (-)-19: M2/M1 = 36-fold, M2/M3 = 96-fold, M2/M4 = 42-fold, M2/M5 = 275-fold). In addition, compound (-)-19 showed 35-fold lower affinity at histamine H1 receptors (pKi = 5.61) than (S)-dimethindene (pKi = 7.16). Another interesting compound is the fluoroethyl derivative 20 (pKi/M2 = 7.49), which also exhibits a higher M2 selectivity (M2/M1 = 19-fold; M2/M3 = 22-fold; M2/M4 13-fold; M2/M5 = 62-fold) than (S)-dimethindene. Unfortunately, compound 20 also shows a high affinity for histamine H1 receptors (pKi = 8.14). The compound with the highest affinity for M2 receptors (pKi = 7.91), the dimethylaminomethylene analogue 31, displayed only a small preference for M2 receptors. In conclusion, compound (-)-19 might be useful to test the hypothesis that blockade of muscarinic M2 receptors in the brain is a viable mechanism by which to produce improved cognition. This second-generation dimethindene analogue might also be the starting point for the development of M2-selective muscarinic antagonists useful for quantifying M2 receptors in the central nervous system with positron emission tomography imaging.