253195-64-1

Upstream product

• 37595-74-7 N,N-phenylbistrifluoromethane-sulfonimide 
• 185198-42-9 6-hydroxy-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acid methyl ester 
• 185198-40-7 1-(2-benzenesulfonyl-2-diazoacetyl)pyrrolidin-2-one 
• 907969-47-5 1-(phenylsulfonylacetyl)pyrrolidin-2-one 
• 292638-85-8 acrylic acid methyl ester 

Downstream Products

• 253195-72-1 methyl-5-oxo-6-phenyl-1,2,3-trihydroindolizine-8-carboxylic acid 
• 612065-23-3 methyl 5-oxo-6-(pyridin-2-ylamino)-1,2,3,5-tetrahydroindolizine-8-carboxylate 
• 612065-19-7 6-(4-methoxy-phenylamino)-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid methyl ester 
• 612065-18-6 5-oxo-6-phenylamino-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid methyl ester 
• 612065-21-1 6-(3,5-dimethoxy-phenylamino)-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid methyl ester 
• 612065-22-2 5-oxo-6-(2-trifluoromethyl-phenylamino)-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid methyl ester 
• 939411-23-1 6-(2-fluorophenyl)-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acid 
• 1442664-04-1 C₁₇H₁₄N₂O₃ 
• 1442664-06-3 C₁₈H₁₉NO₄ 
• 1442664-09-6 C₁₇H₁₇NO₅S 
• 1442664-10-9 C₁₈H₁₈N₂O₄ 
• 1442664-11-0 C₁₉H₁₉NO₅ 
• 1442664-13-2 C₁₇H₁₃ClF₃NO₃ 
• 1442664-14-3 C₁₉H₂₁NO₃ 

Relevant academic research and scientific papers

Synthesis of a 2(1 h)-pyridone library via rhodium-catalyzed formation of isomunchones

Through the use of the dipolar cycloaddition of isomunchones with olefins the 2(1H)-pyridone ring system has been synthesized.(1) The use of different cyclization partners followed by diversification of the initial scaffold has provded libraries of 4-hydroxy-2(1H)-pyridones. There are no examples of this ring system in either PubChem or the MLSMR

BETA-SECRETASE MODULATORS AND METHODS OF USE

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A, B, R3, R4, R5, i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula I, or compositions including them, to a subject. The invention also comprises further embodiments of Formulas II and III, intermediates and processes useful for the preparation of compounds of the invention.

1,3-Dipolar cycloaddition chemistry for the preparation of novel indolizinone-based compounds

Starting from methyl 5-oxo-6-trifluoromethanesulfonyloxy-1,2,3,5- tetrahydroindolizine-8-carboxylate, obtained by a Rh(II)-catalyzed 1,3-dipolar cycloaddition reaction of 1-(2-benzenesulfonyl-2-diazoacetyl)pyrrolidin-2-one and methyl acrylate, several indolo- and furano-fused indolizinones were efficiently prepared. In the first case, a palladium-mediated C-N coupling of the triflate with a variety of substituted anilines provided the desired methyl 5-oxo-6-(arylamino)-1,2,3,5-tetrahydroindolizine-8-carboxylates in high yield. Methyl 6-(2-bromophenylamino)-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate as well as its decarboxylated analogue, 6-(2-bromophenylamino)-2,3-dihydro-1H- indolizin-5-one, were synthesized in excellent yield and were found to undergo an intramolecular Heck cyclization to give 1,2,3,6-tetrahydroindolizino[6,7-b] indol-5-ones. To prepare furano-fused indolizinones, methyl 6-hydroxy-5-oxo-1,2, 3,5-tetrahydroindolizine-8-carboxylate was etherified with different allyl halides, and the resultant allyl ethers were subjected to a thermal Claisen rearrangement to give the corresponding methyl 7-allyl-6-hydroxy-5-oxo-1,2,3,4- tetrahydroindolizine-8-carboxylates. Cyclization under Wacker oxidation conditions afforded methyl 2-methyl-8-oxo-5,6,7,8-tetrahydro-1-oxa-7a-aza-s- indacene-4-carboxylates in near-quantitative yield.

An isomunchnone-based method for the synthesis of highly substituted 2(1H)-pyridones

1-(Benzenesulfonyl-diazoacetyl)-pyrrolidin-2-one was prepared by a diazo transfer of 1-(benzenesulfonylacetyl)-pyrrolidin-2-one with p- acetamidobenzenesulfonyl azide and triethylamine. Treatment of the diazoimide with a catalytic quantity of rhodium(II) acetate resulted in the formation of an isomunchnone dipole, which underwent bimolecular trapping with various dipolarophiles in high yield. The initially formed cycloadducts were not isolable or observed, as they all readily underwent ring opening to give the 3-hydroxy-2(1H)-pyridone ring system. The 3-hydroxy-2(1H)pyridones were readily converted to the corresponding triflates, which function as suitable substrates in various types of palladium-catalyzed cross-coupling reactions. Commercial tetrakis(triphenylphoshine)palladium was found to be a particularly effective catalyst for the cross-coupling with aryl, vinyl, and acetylenic partners. An application of the method to the synthesis of the indolizidine alkaloid (±)-ipalbidine was carried out in eight steps in 17% overall yield. The angiotensin-converting enzyme inhibitor (-)-A58365A was also synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomunchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh2(OAc)4 in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative, which was subsequently converted to the ACE inhibitor in six additional steps.