185198-42-9

Basic information

• Product Name: METHYL 6-HYDROXY-5-OXO-1,2,3,5-TETRAHYDROINDOLIZINE-8-CARBOXYLATE
• Synonyms: METHYL 6-HYDROXY-5-OXO-1,2,3,5-TETRAHYDROINDOLIZINE-8-CARBOXYLATE
• CAS NO: 185198-42-9
• Molecular Formula: C₁₀H₁₁NO₄
• Molecular Weight: 209.2
• Product Categories: pharmacetical
• Mol File: 185198-42-9.mol
• Article Data: 6

Chemical Properties

• Appearance: /
• CAS DataBase Reference: METHYL 6-HYDROXY-5-OXO-1,2,3,5-TETRAHYDROINDOLIZINE-8-CARBOXYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: METHYL 6-HYDROXY-5-OXO-1,2,3,5-TETRAHYDROINDOLIZINE-8-CARBOXYLATE(185198-42-9)
• EPA Substance Registry System: METHYL 6-HYDROXY-5-OXO-1,2,3,5-TETRAHYDROINDOLIZINE-8-CARBOXYLATE(185198-42-9)

Safety Data

• Hazardous Substances Data: 185198-42-9(Hazardous Substances Data)

Upstream product

• 939411-19-5 1-(p-tosyldiazoacetyl)pyrrolidin-2-one 
• 292638-85-8 acrylic acid methyl ester 
• 907969-47-5 1-(phenylsulfonylacetyl)pyrrolidin-2-one 
• 185198-40-7 1-(2-benzenesulfonyl-2-diazoacetyl)pyrrolidin-2-one 

Downstream Products

• 253195-68-5 6-hydroxy-2,3-dihydro-1H-indolizin-5-one 
• 13618-93-4 indolizidine 
• 253195-72-1 methyl-5-oxo-6-phenyl-1,2,3-trihydroindolizine-8-carboxylic acid 
• 612065-22-2 5-oxo-6-(2-trifluoromethyl-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 
• 612065-19-7 6-(4-methoxy-phenylamino)-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid methyl ester 
• 612065-15-3 6-(2-bromo-phenylamino)-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid methyl ester 
• 612065-09-5 6-(2-trifluoromethyl-phenylamino)-2,3-dihydro-1H-indolizin-5-one 
• 612065-08-4 6-(3,5-dimethoxy-phenylamino)-2,3-dihydro-1H-indolizin-5-one 
• 612065-23-3 methyl 5-oxo-6-(pyridin-2-ylamino)-1,2,3,5-tetrahydroindolizine-8-carboxylate 
• 612065-18-6 5-oxo-6-phenylamino-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid methyl ester 
• 612065-07-3 6-(4-nitro-phenylamino)-2,3-dihydro-1H-indolizin-5-one 
• 612065-13-1 N-(5-oxo-1,2,3,5-tetrahydro-indolizin-6-yl)-benzamide 
• 612065-04-0 trifluoro-methanesulfonic acid 5-oxo-1,2,3,5-tetrahydro-indolizin-6-yl ester 

Relevant articles and documents

PYRIDINYL BASED APOPTOSIS SIGNAL-REGULATION KINASE INHIBITORS

Apoptosis signal-regulating kinase 1 (ASK1) activation and signaling have been reported to play an important role in a broad range of diseases including neurodegenerative, cardiovascular, inflammatory, autoimmunity and metabolic disorders. Disclosed herein is the synthesis of pyridinyl derived therapeutic agents that function as inhibitors of ASK 1 as well as their pharmaceutical compositions and methods of use.

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.

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.