212070-75-2

Upstream product

• 4341-76-8 Ethyl 2-butynoate 
• 51608-60-7 phenyl N-tosyl imine 
• 14369-81-4 ethyl 2,3-butadienoate 
• 70-55-3 toluene-4-sulfonamide 
• 51608-60-7 N-(benzylidene)-p-methylbenzenesulfonamide 
• 100-52-7 benzaldehyde 
• 105479-98-9 ethyl 2-(acetoxy(phenyl)methyl)acrylate 
• 50487-71-3 4-methyl-N-(2-propenyl)benzenesulfonamide 

Downstream Products

• 1241684-17-2 C₁₁H₁₃NO₂ 
• 1266677-59-1 C₂₇H₂₃NO₅S 
• 1266677-07-9 C₂₁H₂₃NO₃S 
• 870861-06-6 [2-Phenyl-1-(toluene-4-sulfonyl)-2,5-dihydro-1H-pyrrol-3-yl]-methanol 
• 38597-58-9 2-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

COMPOUNDS, COMPOSITIONS, AND METHODS FOR MODULATING CALCIUM ION HOMEOSTASIS

The present disclosure relates to compounds that are capable of modulating calcium ion homeostasis and treating disorders related thereto. The disclosure further relates to methods of making the aforementioned compounds.

Phosphine-Catalyzed (4+1) Annulation: Rearrangement of Allenylic Carbamates to 3-Pyrrolines through Phosphonium Diene Intermediates

We have developed a phosphine-catalyzed (4+1) annulative rearrangement for the preparation of 3-pyrrolines from allenylic carbamates via phosphonium diene intermediates. We employed this methodology to synthesize an array of 1,3-disubstituted- and 1,2,3-t

Phosphine-catalyzed intramolecular γ-umpolung addition of α-aminoalkylallenic esters: Facile synthesis of 3-carbethoxy-2-alkyl-3- pyrrolines

An array of N-tosylated α-aminoalkylallenic esters was prepared and their cyclization under the influence of nucleophilic phosphine catalysts was explored. The α-aminoalkylallenic esters were prepared through aza-Baylis-Hillman reactions or novel DABCO-me

Discovery of novel, potent, and selective inhibitors of 3-phosphoinositide-dependent kinase (PDK1)

Analogues substituted with various amines at the 6-position of the pyrazine ring on (4-amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)pyrazin-2- ylmethanone were discovered as potent and selective inhibitors of PDK1 with potential as anticancer agents. An early lead with 2-pyridine-3-ylethylamine as the pyrazine substituent showed moderate potency and selectivity. Structure-based drug design led to improved potency and selectivity against PI3Kα through a combination of cyclizing the ethylene spacer into a saturated, five-membered ring and substituting on the 4-position of the aryl ring with a fluorine. ADME properties were improved by lowering the lipophilicity with heteroatom replacements in the saturated, five-membered ring. The optimized analogues have a PDK1 Ki of 1 nM and >100-fold selectivity against PI3K/AKT-pathway kinases. The cellular potency of these analogues was assessed by the inhibition of AKT phosphorylation (T308) and by their antiproliferation activity against a number of tumor cell lines. (Figure presented)

Silver-catalyzed intramolecular aminofluorination of activated allenes

A nice combination: The intramolecular oxidative aminofluorination of allenes using silver catalysis and FN(SO2Ph)2 as the fluorinating reagent has been developed. This reaction represents an efficient method for the synthesis of various 4-fluoro-2,5-dihydropyrrole compounds. Further transformation provided the corresponding fluorinated pyrrole derivatives in good yields (see scheme).

Diversity through a branched reaction pathway: Generation of multicyclic scaffolds and identification of antimigratory agents

A library of 91 heterocyclic compounds composed of 16 distinct scaffolds has been synthesized through a sequence of phosphine-catalyzed ring-forming reactions, Tebbe reactions, Diels-Alder reactions, and, in some cases, hydrolysis. This effort in diversity-oriented synthesis produced a collection of compounds that exhibited high levels of structural variation both in terms of stereochemistry and the range of scaffolds represented. A simple but powerful sequence of reactions thus led to a high-diversity library of relatively modest size with which to explore biologically relevant regions of chemical space. From this library, several molecules were identified that inhibit the migration and invasion of breast cancer cells and may serve as leads for the development of antimetastatic agents.

Mechanism, regioselectivity, and the kinetics of phosphine-catalyzed [3+2] cycloaddition reactions of allenoates and electron-deficient alkenes

With the aid of computations and experiments, the detailed mechanism of the phosphine-catalyzed [3+2] cycloaddition reactions of allenoates and electron-deficient alkenes has been investigated. It was found that this reaction includes four consecutive processes: 1) In situ generation of a 1,3dipole from allenoate and phosphine, 2) stepwise [3+2] cycloaddition, 3) a water-catalyzed [1,2]-hydrogen shift, and 4) elimination of the phosphine catalyst. In situ generation of the 1,3dipole is key to all nucleophilic phosphine-catalyzed reactions. Through a kinetic study we have shown that the generation of the 1,3-dipole is the rate-determining step of the phosphine-cat- alyzed [3 + 2] cycloaddition reaction of allenoates and electron-deficient alkenes. DFT calculations and FMO analysis revealed that an electron-with- drawing group is required in the allene to ensure the generation of the 1,3-dipole kinetically and thermodynamically. Atoms-in-molecules (AIM) theory was used to analyze the stability of the 1,3-dipole. The regioselectivity of the [3 + 2] cycloaddition can be rationalized very well by FMO and AIM theories. Isotopic labeling experiments combined with DFT calculations showed that the commonly accepted intramolecular [1,2]-proton shift should be corrected to a water-catalyzed [1,2]-proton shift. Additional isotopic labeling experiments of the hetero-[3+2] cycloaddition of allenoates and electron-deficient imines further support this finding. This investigation has also been extended to the study of the phosphine-catalyzed [3+2] cycloaddition reaction of alkynoates as the three-carbon synthon, which showed that the generation of the 1,3-dipole in this reaction also occurs by a water-catalyzed process.

A promising new catalyst family for enantioselective cycloadditions involving allenes and imines: chiral phosphines with transition metal-CH2-P: linkages

The racemic rhenium-containing phosphine (η5-C5H5)Re(NO)(PPh3)(CH2PPh3) (3) catalyzes the [3+2] cycloaddition of H2C{double bond, long}C{double bond, long}CHCO2Et and

Ring-closing metathesis toward the synthesis of 2,5-dihydrofuran and 2,5-dihydropyrrole skeletons from Baylis-Hillman adducts

We have developed an efficient method for the synthesis of 2, 5-dihydrofuran and 2,5-dihydropyrrole skeletons from the simply modified Baylis-Hillman adducts via RCM reaction.

A Novel [3+2] Cycloaddition Approach to Nitrogen Heterocycles via Phosphine-Catalyzed Reactions of 2,3-Butadienoates or 2-Butynoates and Dimethyl Acetylenedicarboxylate with Imines: A Convenient Synthesis of Pentabromopseudilin

The reactivity of a new three carbon synthon, generated in situ from the reaction of 2,3-butadienoates 2-butynoates with an appropriate phosphine as the catalyst, toward the electron-deficient imines is described. Triphenylphosphine-catalyzed reaction of methyl 2,3-butadienoate with N-sulfonylimines gave the single [3+2] cycloadduct in excellent yield; tributylphosphine-catalyzed reaction of methyl 2,3-butadienoate or 2-butynoate with N-tosylimines afforded the corresponding [3+2] cycloadduct as the major product along with a small amount of the three components adduct. Aliphatic N-tosylimines gave moderate yield for this reaction. In addition, a new phosphine-catalyzed cyclization reaction of dimethyl acetylenedicarboxylate with N-tosylimines is also described. A reaction mechanism is proposed. Further elaborations of the cycloaddition products and the synthesis of pentabromopseudilin using this method are exemplified.