1246616-73-8

Basic information

• Product Name: (S)-7-hydroxy-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid
• Synonyms: (S)-7-hydroxy-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid;(4R,12aS)-3,4,6,8,12,12a-Hexahydro-7-hydroxy-4-methyl-6,8-dioxo-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid;(4R,12aS)-7-Hydroxy-4-Methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-9-carboxylic acid;Dolutegravir Intermediate2;(4R,12aS)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid;Dolutegravir Intermediates1
• CAS NO: 1246616-73-8
• Molecular Formula: C12H12N2O6
• Molecular Weight: 280.23348
• Mol File: 1246616-73-8.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• CAS DataBase Reference: (S)-7-hydroxy-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-7-hydroxy-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid(1246616-73-8)
• EPA Substance Registry System: (S)-7-hydroxy-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid(1246616-73-8)

Safety Data

• Hazardous Substances Data: 1246616-73-8(Hazardous Substances Data)

Usage

Uses

(4R,12As)-7-Hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2h-pyrido[1'',2'':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic Acid is an intermediate used in the synthesis of Defluoro Dolutegravir (D228715), which is an impurity of Dolutegravir (D528800), a second generation HIV-1 integrase strand transfer inhibitor. Dolutegravir is currently in Phase III clinical trials for the treatment of HIV infection. Dolutegravir has been shown to potently inhibit HIV replication in cells such as peripheral blood mononuclear cells (PBMCs), MT-4 cells and CIP4 cells infected with a self-inactivating PHIV lentiviral vector.

Upstream product

• 52942-64-0 diethyl(ethoxymethylene)oxalacetate 
• 1246616-78-3 C₁₅H₁₇BrN₂O₅ 
• 1246616-77-2 C₁₃H₁₄BrNO₆ 
• 1246616-76-1 C₁₅H₂₀BrNO₇ 
• 1246616-75-0 C₁₅H₂₁NO₇ 
• 1246616-74-9 diethyl 4-oxo-4H-pyran-2,5-dicarboxylate 
• 1246616-71-6 C₁₃H₁₄ClNO₆ 
• 1246616-70-5 C₁₅H₂₀ClNO₇ 
• 134653-70-6 ethyl 2-[(dimethylamino)methylene]-3-oxobutanoate 

Downstream Products

• 1051375-19-9 (4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2′:4,5]pyrazino-[2,1-b][1,3]oxazine-9-carboxamide sodium salt 
• 1051375-16-6 dolutegravir 

Relevant articles and documents

Six-Step Gram-Scale Synthesis of the Human Immunodeficiency Virus Integrase Inhibitor Dolutegravir Sodium

A short and practical synthesis for preparing the active pharmaceutical ingredient dolutegravir sodium was developed. The convergent strategy starts from (R)-3-amino-1-butanol and establishes the BC ring system in a 76% isolated yield over four steps. Ring A was constructed by a one-pot 1,4-addition to diethyl-(2E/Z)-2-(ethoxymethylidene)-3-oxobutandioate and subsequent MgBr2·OEt2-mediated regioselective cyclization. Amide formation with 2,4-difluorobenzylamine was either performed from the free carboxylic acid or through aminolysis of the corresponding ethyl ester. Final salt formation afforded dolutegravir sodium in a 48-51% isolated yield (HPLC purity of 99.7-99.9%) over six linear steps.

METHOD OF PRODUCING PYRONE AND PYRIDONE DERIVATIVES

The present invention provides a pyrone derivative and a pyridone derivative, which are novel intermediates for synthesizing an anti-influenza drug, a method of producing the same, and a method of using the same.