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tert-Butylcyclopentane derivatives. Part 8. Synthesis of tert-butylcyclopentane-fused pyrimidin-4-ones

In the reactions of ethyl (1R*,2S*,45*)-2-amino-4-tert-butyl-1-cyclopentanecarboxylate (4) or (1R*,3S*,5S*)-3-tert-butyl-6-azabicyclo[3.2.0]heptan-7-one (2) or (1R*,2S*,4S*)-2-amino-4-tert-butyl-1-cyclopentanecarboxamide (6) with imidates or triethyl orthobenzoate, tert-butylcyclopentane-fused dihydropyrimidin-4-ones (7a-e) were prepared. The azetidinone (2) with lactim ethers furnished pyrrolo-, pyrido- and azepino[1,2-a]pyrimidin-4-ones (8-10) in ring-enlargement reactions. Ethyl (1R*,2S*,4S*)-2-amino-4-tert-butyl-1-cyclopentanecarboxylate (4) and ethyl (1R*,2S*,4S*)-2-benzylamino-4-tert-butyl-1- cyclopentanecarboxylate (5) and potassium cyanate or phenyl isocyanate or potassium thiocyanate or phenyl isothiocyanate, yielded pyrimidine-2,4-diones or 2-thioxopyrimidin-4-ones (11-22).

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TRICYCLIC INHIBITORS OF THE BCL6 BTB DOMAIN PROTEIN-PROTEIN INTERACTION AND USES THEREOF

The present application relates to compounds of Formula (I) or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, to compositions comprising these compounds or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, and various uses in the treatment of diseases, disorders or conditions that are treatable by inhibiting interactions with BCL6 BTB, such as cancer.

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HETEROBICYCLIC ALKYLTHIO-BRIDGED ISOXAZOLINES

Disclosed are compounds of Formula 1, N-oxides, and salts thereof, wherein J is and R1, R2, R3, R4, R5, R6, R7, R8a, R8b, R8c, G1, G2, G3, G4, G5, G6, Q1, Q2, Q3, Q4, W1, W2, Y1, Y2, Y3, m and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling undesired vegetation comprising contacting the undesired vegetation or its environment with an effective amount of a compound or a composition of the invention.

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Diethoxyphosphinyl acetic acid hydrazide: A uniquely versatile reagent for the preparation of fused [5,5]-, [5,6]-, and [5,7]-3-[(E)-2-(arylvinyl)]-1,2,4- triazoles

Diethoxyphosphinyl acetic acid hydrazide is a unique reagent that provides a convenient and efficient process to prepare fused [5,5]-, [5,6]-, and [5,7]-3-[(E)-2-(arylvinyl)]-1,2,4-triazoles from aldehydes and alkoxyimines. The process involves three steps without isolation of any intermediates to afford 1,2,4-triazoles in modest to excellent overall yield.

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Acetylcholinesterase inhibition by fused dihydroquinazoline compounds

A new type of dihydroquinazoline-based inibitor of acetylcholinesterase (AChE) is described. These compounds were designed to interact with the catalytic site of AChE in a manner similar to the known inhibitor tacrine. In a manner analogous to the potency enhancement obtained by addition of chlorine atoms to the tacrine molecule, a 3-chloro derivative of the parent hexahydroazepino[2,1-b]quinazoline structure was found to be about 8 times more potent as an AChE inhibitor than the unsubstituted compound.

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New method of preparation of C2F5Li and its reactions with cyclic imines and lactims: Synthesis of alpha-pentafluoroethyl proline

Addition of pentafluoroethyllithium to cyclic imines leads to pentafluoroethyl substituted pyrrolidines, piperidines and azepanes while reaction of cyclic lactims gives rise to 2-pentafluoroethyl imines. Oxidative cleavage of 2-furyl-2-pentafluoroethyl pyrrolidine has been found to be an effective method for the preparation of a racemic alpha-pentafluoroethyl proline.

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Synthesis of 2-(omega-aminoalkyl)imidazolin-4-ones by ring chain transformation of lactam derivatives with alpha-aminoamides

Reaction of N-methylamides of biogenic (S)-alpha-aminoacids 3 with lactam acetals 1 or lactim ethers 2 gives three types of products, i.e. N-methyl-alpha-lactamiminoamides 5 by condensation, 2-(omega-aminoalkyl)imidazolin-5-ones 7 or 2-(omega-lactamiminoalkyl)imidazolin-4-ones 8 by ring chain transformation. All products represent novel optically active derivatives of biogenic alpha-aminoacids.

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N-heterocyclic carbene-catalyzed annulation of alpha-cyano-1,4-diketones with ynals

In this paper, the first stereoselective annulation reaction between r-cyano-1,4-diketones and ynals, mediated by catalytic amounts of a triazolium salt precatalyst and cocatalytic amounts of a weak carboxylate base, is disclosed. The title transformation proceeds smoothly under mild reaction conditions and generates three contiguous stereogenic centers, one of which is a quaternary acetal carbon. This reaction tolerates a wide variety of electronically distinct substituents on both reaction partners and affords privileged bicyclic scaffolds in 61-90% isolated yields and with up to 20:1 diastereomeric preference.

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Pyrroline – Wikipedia,
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Facile synthesis of 4H-1,2,4-benzothiadiazine-1,1-dioxides

o-Bromoarylsulfonylated amidines prepared either by acylation of amidine with o-bromoarylsulfonyl chloride or through the reaction of o-bromoarylsulfoamide with lactime ether underwent Cu(I)-catalyzed intramolecular cyclization to give 4H-1,2,4-benzothiadiazine-1,1-dioxides in good yield. By varying substituents on arylsulfonyl moieties, amidines, and lactime ethers, a small library of structurally diverse 4H-1,2,4- benzothiadiazine-1,1-dioxide derivatives was prepared.

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Absence of Stereoelectronic Control in Hydrolysis of Cyclic Amidines

According to Deslongchamps’ theory of stereoelectronic control, preferentioal cleavage of a tetrahedral intermediate occurs when there are two lone pairs antiperiplanar to the leaving group.For reasons presented (Perrin and Arrhenius, J.Am.Chem.Soc. 1982, 104, 2839), product studies of hydrolysis of cyclic amidines can test this theory, and initial results supported it.However, those results are ambiguous, owing to a mismatch of leaving abilities.We now find that hydrolysis of three six-membered ring amidines bearing matched leaving groups produces predominantly aminoamide, the product of ring cleavage, and only 3-9percent lactam, as expected from the theory.In contrast, hydrolysis of three five- or seven-membered ring amidines produces substantial (ca. 50percent) lactam.Despite attempts to accomodate these results to the theory, it is concluded that there is no general requirement for two lone pairs antiperiplanar to the leaving group and that stereoelectronic control, even in six-membered ring amidines, contributes less than 2 kcal/mol.

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