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N-(AZAARYL)CYCLOLACTAM-1-CARBOXAMIDE DERIVATIVE, PREPARATION METHOD THEREFOR, AND USE THEREOF

An N-(azaaryl)cyclolactam-1-carboxamide derivative having a structure of formula (I), a preparation method therefor, and a use thereof are disclosed in the application. Each substituent are defined in the specification and claims. The series of compounds of the application can be widely applied in the preparation of drugs for treating cancer, tumor, autoimmune disease, metabolic disease or metastatic disease, particularly for treating ovarian cancer, pancreatic cancer, prostate cancer, breast cancer, cervical cancer, glioblastoma, multiple myeloma, metabolic disease, neurodegenerative disease, primary tumor site metastasis or osseous metastasis cancer, and are expected to be developed into a new generation of CSF-1R inhibitor drugs.

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

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Oxidation of Alkyl Trimethylsilyl Ketene Acetals with Lead(IV)

Alkyl trimethylsilyl ketene acetals generated from either esters or lactones react with lead(IV) acetate (LTA) or lead(IV) benzoate (LTB) to afford useful yields of the corresponding alpha-carboyloxy esters and alpha-carboyloxy lactones.Yields of the reaction products are optimized by use of the appropriate solvent (methylene chloride or benzene) during oxidation.Alkyl groups such as methyl, ethyl, and tert-butyl are all compatible with the procedure, and lactones containing five-, six-, and seven-membered rings give good yields of oxidation products.

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

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Metalated nitrile and enolate chlorinations

(Figure presented) Metalated nitriles and enolates rapidly and efficiently abstract chlorine from 2-chloro-2-fluoro-2-phenylacetonitrile to afford a diverse range of chloronitriles and chloroesters. The method provides the first general anionic chlorination of alkylnitriles, tolerates numerous functional groups, and addresses the challenge of synthesizing alpha-chloronitriles under mild conditions.

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

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Scope and mechanism of direct indole and pyrrole couplings adjacent to carbonyl compounds: Total synthesis of acremoauxin A and oxazinin 3

Full details are provided for a recently invented method to couple indoles and pyrroles to carbonyl compounds. The reaction is ideally suited for structurally complex substrates and exhibits high levels of chemoselectivity (functional group tolerability), regioselectivity (coupling occurs exclusively at C-3 of indole or C-2 of pyrrole), stereoselectivity (substrate control), and practicality (amenable to scaleup). In addition, quaternary stereocenters are easily and predictably generated. The reaction has been applied to a number of synthetic problems including total syntheses of members of the hapalindole family of natural products, ketorolac, acremoauxin A, and oxazinin 3. Mechanistically, this coupling protocol appears to operate by a single electron-transfer process requiring generation of an electron-deficient radical adjacent to a carbonyl which is then intercepted by an indole or pyrrole anion.

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

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2-Sulfonylpyrimidines Target the Kinesin HSET via Cysteine Alkylation

Supernumerary centrosomes are a source of aneuploidy, and cells have adopted different mechanisms to avoid multipolar mitoses. The kinesin HSET is required for pseudo-bipolar mitoses in cancer cells with amplified centrosomes and suppression of HSET activity is regarded a potential anti-cancer approach. We report the identification of 2-sulfonylpyrimidine inhibitors of HSET enzymatic activity. HSET inhibition results in establishment of multipolar mitoses and simultaneous inhibition of the kinesin Eg5 restored bipolar spindle formation. Correlation of structure to activity revealed that the 2-sulfonylpyrimidinyl group is required for the activity of the compound class and that 2-sulfonylpyrimidines covalently modify HSET. In addition, these electrophiles react with glutathione, thereby causing oxidative stress. This general reactivity needs to be taken into account if 2-sulfonylpyrimidines will be employed in the development of biologically active small molecules.

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

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Evidence for Extensive Recombination of the Ring-opened to the Original Cyclic Molecular Ions of 2-Substituted Piperidines and Pyrrolidines after Electron Impact

The unusually preferred formation of (M-alkyl)(1+) ions by alpha-fission of 2,2-dialkyl-substituted N-ethyl-piperidines (2) and -pyrrolidines (3) and the virtual absence of ring degradation products is caused by facile recombination of the ring-opened to the original cyclic molecular ions.Suppression of ring opening of the initially formed molecular ions or conversion of the ring-opened into other isomeric molecular ions as explanations of the mass spectrometric behaviour of (2) and (3) are excluded.

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

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Synthetic approaches to the daphnane and tigliane diterpenes from aromatic precursors

Synthetic studies toward the daphnane and tigliane diterpenes, a large family of natural products from the plant families Euphorbiaceae and Thymelaeaceae, are reported. Retrosynthetic analysis traced these molecules back to an aromatic precursor and several routes were explored in the forward direction to access such motifs. Two strategies ultimately proved capable of forging complex 5,7,6-fused tricyclic ring systems, one of which proceeded in only seven steps.

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

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Samarium(II)-mediated 4-exo trig ketyl-olefin cyclisation of unsaturated aldehydes. A general, stereoselective synthesis of functionalised cyclobutanols

gamma,delta-Unsaturated aldehydes having a quaternary centre in either the alpha or beta-position, have been prepared from substituted gamma-butyrolactones and undergo efficient 4-exo-trig ketyl-olefin cyclisation on treatment with samarium(II) iodide to give functionalised cyclobutanols. In all cases cyclisation occurs with complete diastereocontrol to give anti-cyclobutanol products. In the cyclisation of substrate 4ab, significant stereochemical control is achieved at three contiguous chiral centres. Both unsaturated esters and vinyl sulfones have been employed as substrates in the reaction.

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Tetrahydrofuran – Wikipedia,
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A Comprehensive Study on Metal Triflate-Promoted Hydrogenolysis of Lactones to Carboxylic Acids: From Synthetic and Mechanistic Perspectives

Direct hydrogenolysis of lactone to carboxylic acid (i.e., hydrogenolysis of the Calkoxy-O bond with the carbonyl group untouched) is generally difficult, as the current strategies employing Br¡ãnsted acids as the catalyst usually require harsh conditions such as a high temperature and a high H2 pressure. Herein, we report a developed solvent-free catalytic transformation, in which W(OTf)6 is believed to promote the hydrogenolysis process. This strategy could efficiently hydrogenate lactones to carboxylic acids under extra mild conditions (e.g., a reaction temperature of <150 C and 1 atm of H2) and showed a broad substrate scope. In addition, the catalytic protocol can be further applied to the hydrogenolysis of polyhydroxyalkanoate, as a renewable polymer, to the corresponding straight-chain carboxylic acids. An extensive mechanistic study was subsequently performed, and the density functional theory calculations revealed a reaction pattern, including the complete cleavage of the C=O bond with the assistance of the W(OTf)6 catalyst. Moreover, the key intermediate created in the mechanism, as an oxonium with an OTf moiety, was successfully detected by electrospray ionization mass spectra. Through a comparison with the Br¡ãnsted acid-catalyzed system, the study confirmed that the existence of the OTf moiety can significantly lower the barriers associated with the rearrangement and elimination processes. Meanwhile, emphasis was placed on the critical role that the anion plays, as well as the fact that the anion effect is directly related to the chemoselectivity. We¡¯ll also look at important developments in the pharmaceutical industry because understanding organic chemistry is important in understanding health, medicine, the role of 1679-47-6, and how the biochemistry of the body works.COA of Formula: C5H8O2

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

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Highly Enantioselective Intermolecular Cu(I)-Catalyzed Cyclopropanation of Cyclic Enol Ethers. Asymmetric Total Synthesis of (+)-Quebrachamine

A set of cyclic enol ethers derived from 2,3-dihydrofuran 35 and 3,4-dihydropyran 8 with a varying substitution pattern at the olefinic system were synthesized. Evans’s ligand 5 with Cu(I)OTf was found to be an effective catalyst in the cyclopropanation reaction between cyclic enol ethers 14, 19, 28-31, and 33 and ethyl diazoacetate 6 to give diastereoselectivities up to exo/endo = 95:5 and enantioselectivities higher than 95% in nearly all cases. Because of the selective building of a quarternary carbon center and good yields in the formation of bicyclic structures 34c-h, the reaction was used as a key step in the asymmetric synthesis of (+)-quebrachamine 7, an indole alkaloid of the Aspidosperma family. After acid-induced ring opening of bicyclic compound 34f to lactone 40 followed by LiAlH4 reduction to the masked aldehyde 41, a reaction with tryptamine gave intermediate 42. This alcohol was efficiently converted into the indole alkaloid (+)-quebrachamine 7 in an overall yield of 37% starting from the chiral synthon 34f. Moreover it revealed the absolute configuration of the quarternary center of the cyclopropanation product 34f to be S.

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