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Palladium-Catalyzed Directed C(sp3)-H Arylation of Saturated Heterocycles at C-3 Using a Concise Optimization Approach

Saturated heterocycles, such as THFs, pyrrolidines, piperidines and THPs, are essential components of many biologically active compounds. Examples of C-H functionalization on these important ring systems remain scarce, especially at unactivated positions. Here we report the development of conditions for the palladium-catalyzed stereoselective C(sp3)-H arylation at unactivated 3-positions of 5- and 6-membered N- and O-heterocycles with aminoquinoline directing groups. Subtle differences in substrate structures altered their reactivity significantly; and different conditions were required to achieve high yields in each case. Successful conditions were developed using a short empirical optimization approach to cover reaction space with a limited set of variables. Excellent cis-selectivity was achieved in all cases, except for the THP substrate where minor trans-products were formed through a different palladacyclic intermediate. Here, differences in reactivity and selectivity with other directing groups were examined.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Synthesis and SAR of arylaminoethyl amides as noncovalent inhibitors of cathepsin S: P3 cyclic ethers

The synthesis and structure-activity relationship of a series of arylaminoethyl amide cathepsin S inhibitors are reported. Optimization of P3 and P2 groups to improve overall physicochemical properties resulted in significant improvements in oral bioavailability over early lead compounds. An X-ray structure of compound 37 bound to the active site of cathepsin S is also reported.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Catalyst-Free Decarboxylation of Carboxylic Acids and Deoxygenation of Alcohols by Electro-Induced Radical Formation

Electro-induced reduction of redox active esters and N-phthalimidoyl oxalates derived from naturally abundant carboxylic acids and alcohols provides a sustainable and inexpensive approach to radical formation via undivided electrochemical cells. The resulting radicals are trapped by an electron-poor olefin or hydrogen atom source to furnish the Giese reaction or reductive decarboxylation products, respectively. A broad range of carboxylic acid (1, 2, and 3) and alcohol (2 and 3) derivatives are applicable in this catalyst-free reaction, which tolerated a diverse range of functional groups. This method features simple operation, is a sustainable platform, and has broad application.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Tuning the chiral cavity of macrocyclic receptor for chiral recognition and discrimination

(Chemical Equation Presented) The size and shape of the chiral cavity of a macrocyclic receptor were tuned by the alteration of the binaphthyl moiety to improve the chiral recognition/discrimination ability. For example, host 3 with the 3,5-bis(trifluoromethyl)phenyl group at the 3,3?-positions showed improved enantioselectivity for small molecules such as 2-chloropropionic acid and methyl lactate as evaluated by the binding constants. This host 3 also had an excellent ability as an NMR chiral solvating agent.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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THERAPEUTIC COMPOUNDS

Compounds disclosed herein including compounds of Formula I: and salts thereof are provided. Pharmaceutical compositions comprising compounds disclosed herein, processes for preparing compounds disclosed herein, intermediates useful for preparing compounds disclosed herein and therapeutic methods for treating an HIV infection using compounds disclosed herein are also provided.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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PYRROLIDINE DERIVATIVES AS DUAL NK1/NK3 RECEPTOR ANTAGONISTS

The invention relates to pyrrolidine derivatives of formulawherein R1,R2,R3,n, and o are defined in the specification and to pharmaceutically active acid-addition salts thereof. Compounds of formula I have a high affinity simultaneously to both the NK1 and the NK3 receptors (dual NK1/NK3 receptor antagonists), useful in the treatment of schizophrenia.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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The bridge ring piperazine derivative or its salt and its preparation and use (by machine translation)

The invention belongs to the technical field of chemical medicine, relates to bridge piperazine derivative or its salt and its preparation method, and the states the bridge arch piperazine derivative or a salt thereof in the preparation in the treatment of diseases associated with the ROR gamma t use in the medicament. By experiment, the results display, of the bridge of the present invention can effectively inhibit the piperazine derivatives ROR gamma t protein receptor, regulating Th17 cell differentiation, inhibiting IL – 17 production, can be further used to treat ROR gamma t-mediated inflammation-related drug for the treatment of such diseases, especially suitable for the treatment of multiple sclerosis, rheumatoid arthritis, collagen induced arthritis, psoriasis, inflammatory bowel disease, encephalomyelitis, cloning disease, asthma, inflammation-related diseases such as cancer. (by machine translation)

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Chiral ammonium hypoiodite salt-catalyzed enantioselective oxidative cycloetherification to 2-acyl tetrahydrofurans

2-Acyl tetrahydrofuran is a fundamental structure in natural products and pharmaceuticals. We achieved chiral quaternary ammonium hypoiodite salt-catalyzed enantioselective oxidative cycloetherification of delta-hydroxyketone derivatives. The corresponding 2-acyl tetrahydrofurans were obtained in high chemical yield with high enantioselectivity.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Anti-Selective Catalytic Asymmetric Nitroaldol Reaction of alpha-Keto Esters: Intriguing Solvent Effect, Flow Reaction, and Synthesis of Active Pharmaceutical Ingredients

A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and alpha-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active alpha-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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MORPHINAN DERIVATIVE

A compound represented by the following general formula (I), wherein R1 represents hydrogen, C1-10 alkyl, cycloalkylalkyl where the cycloalkyl moiety has 3 to 6 carbon atoms and the alkylene moiety has 1 to 5 carbon atoms, or the like, R2 represents a 4- to 7-membered saturated heterocycle containing one or two heteroatoms which may be the same or different and are selected from N, O, and S, and two or more carbon atoms as ring-constituting atoms, the heterocycle may be substituted with a substituent such as an oxo group, R2 binds to Y via a carbon atom as a ring-constituting atom of R2, R3, R4, and R5, which are the same or different, represent hydrogen; hydroxy; or the like, R6a and R6b, which are the same or different, represent hydrogen or the like, R7 and R8, which are the same or different, represent hydrogen or the like, R9 and R10, which are the same or different, represent hydrogen or the like, X represents O or CH2, and Y represents C(= O) or the like), a tautomer of the compound, a stereoisomer of the compound, a pharmaceutically acceptable salt thereof, or a solvate thereof is used as an anxiolytic, an antidepressant, or the like.

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Reference£º
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem