55130-49-9

Usage

InChI:InChI=1/C11H16O6/c1-4-15-7-8(10(13)16-5-2)9(12)11(14)17-6-3/h7H,4-6H2,1-3H3/b8-7-

Upstream product

• 122-51-0 orthoformic acid triethyl ester 
• 108-56-5 diethyl oxaloacetate 
• 53241-93-3 diethyl 2-hydroxybut-2-enedioate 

Downstream Products

• 67389-92-8 2-[1-[N'-(2,4-Dinitro-phenyl)-hydrazino]-meth-(E)-ylidene]-3-oxo-succinic acid diethyl ester 
• 1246616-73-8 (4R)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12ahexahydro-2H-pyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid 
• 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 
• 62328-19-2 2-oxo-1,2-dihydro-pyrimidine-4,5-dicarboxylic acid diethyl ester 
• 16078-70-9 2-phenyl-2H-pyrazole-3,4-dicarboxylic acid 
• 856957-63-6 6-phenyl-pyridine-2,3,5-tricarboxylic acid 
• 54001-63-7 Pyrimidine-4,5-dicarboxylic acid 
• 114954-08-4 diethyl 8-cyano-7-phenylpyrrolo<1,2-a>pyrimidin-3,4-dicarboxylate 
• 21272-70-8 <(2-Phenyl-hydrazino)-methylen>-oxalyl-essigaesure-diethylester 
• 67389-77-9 2-Oxo-3-[1-phenylamino-meth-(E)-ylidene]-succinic acid diethyl ester 
• 37687-26-6 3,4-bis-(ethoxycarbonyl)pyrazole 
• 16078-69-6 diethyl 1-phenyl-1H-pyrazole-4,5-dicarboxylate 
• 412337-54-3 5-cyano-6-phenyl-pyridine-2,3-dicarboxylic acid diethyl ester 

Relevant academic research and scientific papers

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.

Regioselective synthesis of 4-acyl-1-hydroxy-2,3-benzodioates by chelation-controlled [3+3] annulation of 3-acyl-4-ethoxy-2-oxo-3-enoates with 1,3-bis(trimethylsilyloxy)-1,3-butadienes

4-Acyl-1-hydroxy-2,3-benzodioates were regioselectively prepared by chelation-controlled [3+3] cyclization of 1,3-bis(trimethylsilyloxy)-1,3- butadienes with 3-acyl-4-ethoxy-2-oxo-3-enoates.

The synthesis of 6,9-bis[(aminoalkyl)amino] substituted benzo[g]quinoxaline-, benzo[g]quinazoline- and benzo[g]phthalazine-5,10- diones via regiospecific displacements

The synthesis of 6,9-difluoro substituted benzo[g]quinoxaline-5,10-diones (3A), benzo[g]quinazoline-5,10-diones (3B) and benzo[g]phthalazine-5,10- diones (3C) have been accomplished. Treatment of 3A, 3B or 3C with diamines or N-(t-butoxycarbonyl)ethylenediamine led to the corresponding 6,9- bis[(aminoalkyl)amino]-substituted analogues related to 2A, 2B and 2C, respectively. The mono-substituted derivatives 4h and 4i could be isolated from displacements commencing from 3A. A competitive ring-opening of the pyrimidine ring of 2C occurred during the reaction with N,N- dimethylethylenediamine. Removal of the BOC-protecting group from 2Ac led to the hydrochloride salt 2Ab. A novel synthetic pathway to 6,9- dihydroxybenzo[g]phthalazine-5,10-dione (21a) was developed. Conversion of 21a to the ditosylate 21b was readily accomplished. Treatment of 21b with N,N-dimethylethylenediamine or N-(t-butoxycarbonyl)ethylenediamine led to 2Ca and 2Cc, respectively. Removal of the BOC-protecting group from 2Cc with trifluoroacetic acid followed by ion-exchange led to the hydrochloride salt 2Cb. Treatment of ditosylate 21b with N-(t-butoxycarbonyl)ethylenediamine also led to the mono-substituted analogue 25a along with a small amount of the O-S cleavage product 25b. Treatment of 25a with N,N- dimethylethylenediamine led to the unsymmetrically substituted derivative 25c which was converted into the trifluoroacetate salt 25d.