1093759-68-2

Upstream product

• 123855-51-6 tert-butyl 4-(hydroxymethyl)piperidin-1-carboxylate 
• 6457-49-4 4-piperidinemethanol 
• 24424-99-5 di-tert-butyl dicarbonate 
• 7226-23-5 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone 
• 301673-14-3 tert-butyl 4-iodopiperidine-1-carboxylate 
• 1048970-17-7 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)piperidine-1-carboxylic acid tert-butyl ester 
• 137076-22-3 tert butyl 4-formylpiperidine-1-carboxylate 
• 87120-72-7 1-(tert-butoxycarbonyl)-4-aminopiperidine 
• 1872262-73-1 1-(tert-butyl) 4-(1,3-dioxoisoindolin-2-yl) piperidine-1,4-dicarboxylate 

Relevant academic research and scientific papers

Decarboxylative and Deaminative Alkylation of Difluoroenoxysilanes via Photoredox Catalysis: A General Method for Site-Selective Synthesis of Difluoroalkylated Alkanes

A general method for site-selective difluoroalkylation of alkyl carboxylic redox esters with difluoroenoxysilanes through photoredox-catalyzed decarboxylative reaction has been developed. The reaction can also be extended to aliphatic amine derived pyridinium salts. This method has the advantages of high efficiency, mild reaction conditions, and broad substrate scope, including primary, secondary, and sterically hindered tertiaryl alkyl substrates, providing a general and practical route for applications in organic synthesis and pharmaceutical studies.

Visible light promoted deaminative difluoroalkylation of aliphatic amines with difluoroenoxysilanes

A visible light promoted deaminative strategy for the difluoroalkylation reaction utilizing pyridinium-activated aliphatic primary amines and difluoroenoxysilane as substrates has been developed. This protocol is characteriazed by its mild reaction conditions and broad substrate scope, which converted a diverse array of amine-containing molecules to the alkyl-CF2COPh products. Moreover, the resulting products can be easily transformed into a vast array of structurally novel and interesting difluoro-containing moieties, therefore providing a facile route for applications in medicinal chemistry and the life sciences. This journal is

Copper-Catalyzed Decarboxylative Difluoromethylation

We report herein a highly efficient Cu-catalyzed protocol for the conversion of aliphatic carboxylic acids to the corresponding difluoromethylated analogues. This robust, operationally simple and scalable protocol tolerates a variety of functional groups and can convert a diverse array of acid-containing complex molecules to the alkyl-CF2H products. Mechanistic studies support the involvement of alkyl radicals.

Divergent, Stereospecific Mono- and Difluoromethylation of Boronic Esters

There is considerable interest in incorporating fluorine into agrochemicals and pharmaceuticals to improve their biological properties. Whilst a number of methods have been reported for installing CH2F and CHF2 groups, they are mainly limited to radical reactions, which are invariably racemic. Herein, we report the divergent, stereospecific reaction of fluoroiodomethyllithium with boronic esters to give α-fluoro-boronic esters. These unique intermediates can be readily transformed into the corresponding mono- or difluoromethylated compounds through proto- or fluorodeboronation, respectively. The use of the highly unstable fluoroiodomethyllithium was key to allowing rapid 1,2-migration over competing decomposition of the carbanion. DFT calculations informed and supported the experimental findings.

Copper-Catalyzed Difluoromethylation of Alkyl Iodides Enabled by Aryl Radical Activation of Carbon–Iodine Bonds

The engagement of unactivated alkyl halides in copper-catalyzed cross-coupling reactions has been historically challenging, due to their low reduction potential and the slow oxidative addition of copper(I) catalysts. In this work, we report a novel strategy that leverages the halogen abstraction ability of aryl radicals, thereby engaging a diverse range of alkyl iodides in copper-catalyzed Negishi-type cross-coupling reactions at room temperature. Specifically, aryl radicals generated via copper catalysis efficiently initiate the cleavage of the carbon–iodide bonds of alkyl iodides. The alkyl radicals thus generated enter the copper catalytic cycles to couple with a difluoromethyl zinc reagent, thus furnishing the alkyl difluoromethane products. This unprecedented Negishi-type difluoromethylation approach has been applied to the late-stage modification of densely functionalized pharmaceutical agents and natural products.

Method for difluoroalkylation after fatty amine deamination

The invention discloses a method for difluoroalkylation after fatty amine deamination in the field of organic synthesis. Particularly the method comprises the following steps: by taking simple and easily available fatty amine represented by a formula A as a raw material, reacting the fatty amine with pyranyl tetrafluoroborate represented by a formula B under a heating or room temperature conditionto obtain alkyl pyridinium represented by a formula C; and under the illumination condition, obtaining various difluoroalkyl substituted alkanes, cycloalkanes and derivatives thereof with high yieldby selecting commercially available [Ir(dtbbpy)(ppy)2]PF6 as a catalyst and difluoroenol silyl ether D as a difluoroalkylation reagent. According to the invention, the method is simple and convenientto operate, simple and mild in reaction condition, excellent in functional group compatibility and suitable for large-scale production and synthesis; and fluorine-containing amino acid with potentialapplication value can be obtained through the catalytic synthesis method, and various difluoroalkyl-containing compounds with novel structures and important significance in the fields of medicines, pesticides and materials can be easily obtained through further conversion of the obtained product.

Copper-Catalyzed Deaminative Difluoromethylation

The difluoromethyl group (CF2H) is considered to be a lipophilic and metabolically stable bioisostere of an amino (NH2) group. Therefore, methods that can rapidly convert an NH2 group into a CF2H group would be of great value to medicinal chemistry. We report herein an efficient Cu-catalyzed approach for the conversion of alkyl pyridinium salts, which can be readily synthesized from the corresponding alkyl amines, to their alkyl difluoromethane analogues. This method tolerates a broad range of functional groups and can be applied to the late-stage modification of complex amino-containing pharmaceuticals.

TETRAHYDROISOQUINOLINE KAPPA OPIOID ANTAGONISTS

Potent opioid receptor antagonists of formula (I) and their use as pharmacotherapies for treating depression, anxiety, schizophrenia, eating disorders, and addiction to cocaine, methamphetamine, nicotine, alcohol, and opiates are disclosed. More specifically, the disclosure provides potent and selective kappa opioid receptor antagonist compounds, pharmaceutical compositions of those compounds and uses of those compounds to ameliorate or treat addictions, eating disorders, etc.

BENZOXAZEPINES AS INHIBITORS OF P13K/MTOR AND METHODS OF THEIR USE AND MANUFACTURE

The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds. 9936396.1

BENZOXAZEPINES AS INHIBITORS OF MTOR AND METHODS OF THEIR USE AND MANUFACTURE

The invention is directed to inhibitors of mTOR and pharmaceutically acceptable salts or solvates thereof, as well as methods of using them. The inhibitors are generally of structural formula wherein the combination of R1 and R2 are