90611-60-2

Upstream product

• 67-56-1 methanol 
• 562-46-9 4,4-dimethylcyclohexane-1,3-dione 
• 147426-05-9 4,4-dimethyl-3-(phenylthio)cyclohex-2-en-1-one 
• 1073-13-8 4,4-dimethylcyclohexenone 

Downstream Products

• 1147731-49-4 4,4-dimethyl-3-pent-4-enyl-cyclohex-2-enone 
• 315188-18-2 9-(3-bromo-4-fluorophenyl)-5,5-dimethyl-2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide 
• 86791-38-0 3-methoxy-4,4-dimethylcyclohexa-2,5-dien-1-one 

Relevant academic research and scientific papers

Efficient formal synthesis of (±)-hyphodermin B

An efficient formal synthesis of hyphodermin B 1, a metabolite of Hyphoderma radula, has been completed in 15% overall yield. The tricyclic carbon skeleton 3 was rapidly assembled from a novel vinyl enone via a Diels-Alder reaction, followed by dehydrogen

N-(1-(METHYLSULFONYL)PIPERIDIN-4-YL)-4,5-DI HYDRO-1H-IMIDAZO[4,5-H]QUINAZOLIN-8-AMINE DERIVATIVES AND RELATED COMPOUNDS AS CYCLIN-DEPENDENT KINASE 2 (CDK2) INHIBITORS FOR TREATING CANCER

The present application provid es tricyclic amine compounds of formula (I) as inhibitors of cyclin-dependent kinase 2 (CDK2) for treating cancer. Preferred compounds are N-(1-(methylsulfonyl)piperidin-4- yl)-4,5-dihydro-lH-imidazo[4,5-h]quinazolin-8-amine and the corresponding 6,8-dihydro-5H-pyrazolo[3,4-h]quinazolin-2-amine, 6,8- dihydropyrazolo[4',3':4,5]pyrano[3,2-d]pyrimidin-2-amine and 1,4- dihydroimidazo[4',5': 4,5]pyrano[3,2-d]pyrimidin-8-amine derivatives of formulae (IVa) to (IVd). The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 128 to 166; examples 1 to 32, A and B1 to B10; table 1). Exemplary compound are e.g.: N-(1-(ethylsulfonyl)piperidin-4-yl)-l,2-dimethyl-4,5-dihydro-1H- imidazo[4,5-h]quinazolin-8-amine (example 1) 8-Methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8-dihydro-5H- pyrazolo[3,4-h]quinazolin-2-amine (example 9) 8-Methyl-N-(1-(methylsulfonyl)piperidin-4-yl)-6,8- dihydropyrazolo[4',3':4,5]pyrano[3,2-d]pyrimidin-2-amine (example 10) 1-cyclopropyl-N-(1-(methylsulfonyl)piperidin-4-yl)-l,4- dihydroimidazo[4',5':4,5]pyrano [3,2-d]pyrimidin-8-amine (example 26).

Lewis Acid Catalyzed Enantioselective Photochemical Rearrangements on the Singlet Potential Energy Surface

The oxadi-methane rearrangement of 2,4-cyclohexadienones to bicyclic ketones was found to proceed with high enantioselectivity (92-97% ee) in the presence of catalytic amounts of a chiral Lewis acid (15 examples, 52-80% yield). A notable feature of the transformation is the fact that it proceeds on the singlet hypersurface and that no triplet intermediates are involved. Rapid racemic background reactions were therefore avoided, and the catalyst loading could be kept low (10 mol %). Computational studies suggest that the enantioselectivity is determined within a Lewis acid bound singlet intermediate via a conical intersection. The utility of the method was demonstrated by a concise synthesis of the natural product trans-chrysanthemic acid.

Synthesis of (±)- and (+)-perovskone

A biomimetic synthesis of the triterpene (±)-perovskone was achieved featuring a remarkable polycyclization process in which three rings, four bonds, and five stereocenters were created in a single operation in 82% yield. This convergent synthesis required 16 steps, starting from vanillin, and proceeded in 9% overall yield. A second route to prepare optically active quinone 2 took 15 steps in 36% overall yield and featured a palladium-catalyzed reductive allylic transposition to establish the C-5 chirality stereospecifically. Quinone (-)-2 was converted to (+)-perovskone (1) via a polycyclization cascade, which created four rings, five bonds, and six stereocenters in a single operation in 50% yield.

SPIRO COMPOUNDS AND PHARMACEUTICAL USE THEREOF

The Spiro compound represented by the following general formula [Ia], its pharmaceutically acceptable salt or a solvate thereof

Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9-hexahydrothieno[3,2-b]quinoline-8(4H)-one 1,1-dioxide K ATP channel openers: Discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9-hexahydrothieno[3,2-b] quinolin-8(4H)-one 1,1-dioxide (A-278637), a potent KATP opener that selectively inhibits spontaneous bladder contractions

Structure-activity relationships were investigated on a novel series of sulfonyldihydropyridine-containing KATP openers. Ring sizes, absolute stereochemistry, and aromatic substitution were evaluated for K ATP activity in guinea pig bladder cells using a fluorescence-based membrane potential assay and in a pig bladder strip assay. The inhibition of spontaneous bladder contractions in vitro was also examined for a select group of compounds. All compounds studied showed greater potency to inhibit spontaneous bladder contractions relative to their potencies to inhibit contractions elicited by electrical stimulation. In an anesthetized pig model of myogenic bladder overactivity, compound 14 and (-)-cromakalim 1 were found to inhibit spontaneous bladder contractions in vivo at plasma concentrations lower than those that affected hemodynamic parameters. Compound 14 showed approximately 5-fold greater selectivity than 1 in vivo and supports the concept that bladder-selective KATP channel openers may have utility in the treatment of overactive bladder.

Mild acetalisation of mono and dicarbonyl compounds catalysed by titanium tetrachloride. Facile synthesis of β-keto enol ethers

The use of TiCl4, as a catalyst for the acetalisation, at room temperature, of carbonyl compounds is reported. Cyclic ketones and cyclic 1,4-diketones easily afford dimethyl acetals, but cyclic 1,3-diketones give β-keto enol ethers. Additionally, aryl ketones and acyclic ketones failed to react. β-keto aldehydes can be monoprotected either as β-keto enol ethers or β-keto dimethyl acetals depending on the reaction time and catalyst amount. Some mechanistic features are accounted for.

The regioselectivity of the Birch reduction

The reaction mechanism of the Birch reduction was investigated with a view of determinig how the regioselectivity is controlled. Regioselectivity is determined in the first step of radical anion protonation and in the second step of cyclohexadienyl carbanion protonation. It was ascertained that the rate-determining step of the Birch reduction of anisole was radical anion protonation, consistent with the observation of Krapcho and Bothner-By in the case of benzene reduction. A new approach to determining the regioselectivity of the two steps of the Birch reduction was devised. This was predicated on an enhanced primary deuterium isotope effect anticipated for radical anion protonation relative to that expected for cyclohexadienyl carbanion protonation. The approach utilized a partially deuterated medium. The method was applied to the reductions of anisole, 1,3-dimethoxybenzene, 3-methoxytoluane, and 2-methoxynaphthalene. The basic assumption of greater selectivity of the radical anion of the first step relative to the carbanion of the second step was explored in the cases of benzene and anisole and confirmed. In the examples studied, ortho protonation of the radical anion was found to predominate. With a view of understanding the regioselectivity of the two steps, quantum mechanical computations were carried out on several facets of the reaction. Electron density distributions of the radical anions were determined as well as the energies of radical products of some radical anion protonations. Similarly, the energies were obtained for the partially protonated radical anion species at several points along the reaction coordinate. In addition, electron densities were obtained for cyclohexadienyl anion. Theory was then correlated with experiment.