159454-98-5

Upstream product

• 867-13-0 diethoxyphosphoryl-acetic acid ethyl ester 
• 637-88-7 1,4-Cyclohexanedione 
• 1099-45-2 ethyl (triphenylphosphoranylidene)acetate 
• 5927-18-4 trimethyl phosphonoacetate 
• 7647-01-0 hydrogenchloride 
• 51656-91-8 ethyl 1,4-dioxaspiro[4,5]dec-8-ylideneacetate 
• 923584-02-5 8-(bromomethylene)-1,4-dioxaspiro[4.5]decane 
• 4746-97-8 cyclohexanedione monoethylene ketal 
• 64-17-5 ethanol 
• 201230-82-2 carbon monoxide 
• 1407169-65-6 4-(bromomethylidene)cyclohexanone 
• 678967-25-4 3-(1-Phenyl-vinyl)-1,2,5-trioxaspiro[5.5]undec-9-one 
• 868696-27-9 [3-(1-phenyl-vinyl)-1,2,5-trioxa-spiro[5.5]undec-9-ylidene]-acetic acid ethyl ester 

Downstream Products

• 159454-99-6 ethyl 4,4-dimethoxycyclohexylideneacetate 
• 51656-91-8 ethyl 1,4-dioxaspiro[4,5]dec-8-ylideneacetate 
• 16700-13-3 ethyl 2-(4-hydroxycyclohexylidene)acetate 
• 1422253-49-3 ethyl (Z)-4-carboxymethylene-ε-caprolactone 

Relevant academic research and scientific papers

Solvent effects in reactions of diketones with Wittig and Wittig-Horner reagents

In a series of reactions between Wittig or Wittig-Horner (Wadsworth-Emmons) reagents and diketones it was found that out of the five solvents tested, for the Wittig reagents, namely dichloromethane, toluene, ethanol, dimethylformamide, and pyridine, only

Scalable and divergent total synthesis of (+)-colletoic acid, a selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor

An efficient and divergent total synthesis of (+)-colletoic acid, a selective 11-β hydroxysteroid dehydrogenase 1 (11-βHSD1) inhibitor, is presented along with its biological activity at the whole-cell level. A scalable, asymmetric synthetic strategy was designed featuring a diversity-oriented synthesis utilizing a diastereoselective intramolecular 5-exo-Heck reaction as the key step to provide the quaternary spirocenter intermediate 9 in multigram scale, thus establishing a platform for further structure-activity relationship studies and providing access to other acorane family members.

Conformational-Analysis-Guided Discovery of 2,3-Disubstituted Pyridine IDO1 Inhibitors

IDO1 inhibitors have shown promise as immunotherapies for the treatment of a variety of cancers, including metastatic melanoma and renal cell carcinoma. We recently reported the identification of several novel heme-displacing IDO1 inhibitors, including the clinical molecules linrodostat (BMS-986205) and BMS-986242. Both molecules contain quinolines that, while being present in successful medicines, are known to be potentially susceptible to oxidative metabolism. Efforts to swap this quinoline with an alternative aromatic system led to the discovery of 2,3-disubstituted pyridines as suitable replacements. Further optimization, which included lowering ClogP in combination with strategic fluorine incorporation, led to the discovery of compound 29, a potent, selective IDO1 inhibitor with robust pharmacodynamic activity in a mouse xenograft model.

HETEROCYCLIC COMPOUNDS AS INHIBITORS OF HPK1

This disclosure relates to heterocyclics as inhibitors of HPK1, in particular relates to a compound of Formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising said compound that useful for treatment of HPK1 mediated diseases and conditions such as cancer. (I)

Preparation method of 2-(4-aminocyclohexyl)-ethyl acetate

The invention provides a preparation method of 2-(4-aminocyclohexyl)-ethyl acetate, and belongs to the field of pharmaceutical chemistry. According to the preparation method, 1, 4-cyclohexanedione istaken as an initial raw material, and Wittig reaction, condensation reaction, catalytic hydrogenation, and the like are carried out so as to obtain 2-(4-aminocyclohexyl)-ethyl acetate. The purity of obtained 2-(4-aminocyclohexyl)-ethyl acetate is high; it is beneficial for preparation of dopamine receptor ligand drugs; the raw materials are widely available; operation is simple; reaction conditions are mild; and industrial application prospect is promising.

A new type of stereoselectivity in Baeyer-Villiger reactions: Access to E- and Z-olefins

A new concept for accessing configurationally defined trisubstituted olefins has been developed. Starting from a common ketone precursor of the type 4-ethylidenecyclohexanone, Baeyer-Villiger monooxygenases are employed as catalysts in diastereoselective Baeyer-Villiger reactions leading to the corresponding E- or Z-configurated lactones. Wild-type cyclohexanone monooxygenase (CHMO) as catalyst delivers the E-isomers and a directed evolution mutant the opposite Z-isomers. Subsequent transition metal-catalyzed chemical transformations of a key product containing a vinyl bromide moiety provide a variety of different trisubstituted E- or Z-olefins. A model based on QM/MM sheds light on the origin of this unusual type of diastereoselectivity. In contrast to this biocatalytic approach, traditional Baeyer-Villiger reagents such as m-CPBA fail to show any selectivity, 1:1 mixtures of E- and Z-olefins being formed. Copyright

Microwave-assisted regioselective olefinations of cyclic mono- and di-ketones with a stabilized phosphorus ylide

A number of cyclic mono- and di-ketones underwent regioselective olefination with (carbethoxyethylidene)triphenylphospharane under controlled microwave heating. The Wittig reaction of 4-substituted cyclohexanones or 1,2- and 1,4-cyclohexanediones with the ylide at 190 °C for 20 min in MeCN afforded the exocyclic olefins in >94:6 isomer ratios. On the other hand, the same reactions carried out at 230 °C for 20 min in the presence of 20 mol % DBU furnished the endocyclic olefins in >83:17 isomer ratios. The base-mediated isomerization of the exocyclic olefins into the endocyclic isomers was primarily driven by thermodynamic stability of the products and the effect of ring structures on deconjugation was examined.

Protection of the carbonyl group as 1,2,4-trioxane and its regeneration under basic conditions

(Chemical Equation Presented) An experimental protocol demonstrating the protection of the carbonyl group as 1,2,4-trioxane, the stability of the protecting group under a variety of reaction conditions, and the regeneration of the carbonyl group with Triton B in THF at room temperature is presented. The method provides a useful alternative for the protection of carbonyl compounds having acid-sensitive moieties.

Cytotoxic analogues of 2,6-bis(arylidene)cyclohexanones

A series of 2,6-bis(arylidene)cycloalkanones (1) and related compounds containing one or two substituents at the four position of the cyclohexyl ring were prepared and shown to display cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In some of the series of compounds, positive correlations were noted between the potencies of the enones and the magnitude of the Hammett σ values of the aryl substituents. Four representative compounds were cytotoxic to a number of human tumours in vitro, particularly towards colon cancer and leukemic cells. A noteworthy feature of the compounds prepared in this study is that, in general, they were well tolerated when administered to rodents. A number of lead molecules emerged from this investigation as well as guidelines for future expansion of these series of compounds.

A ring closing metathesis based approach for the spiroannulation of cyclopentanes and cyclohexanes. Formal synthesis of (±)-acorones

An efficient ring closing metathesis (RCM) reaction based approach was developed for the spiroannulation of cyclopentanes and cyclohexanes and its utility demonstrated in the formal synthesis of the spirosesquiterpenes acorones.