Highly selective synthesis of 2-substituted-5-hydroxy-6-oxo-1,6- dihydropyrimidine-4-carboxylic acid derivatives using a novel protected dihydroxyfumarate

Tetrahedron Letters

Volumn 45, Issue 31, 2004, Pages 6023-6025

  Dreher, Spencer D ^a   Ikemoto, Norihiro ^a   Gresham, Venita ^a   Liu, Jinchu ^a   Dormer, Peter G ^a   Balsells, Jaume ^a   Mathre, David ^a   Novak, Thomas J ^a   Armstrong III, Joseph D ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Fumarate; Pyrimidine; Pyrimidinone

Indexed keywords

2 PHENYL 5,6 DIHYDROXYPYRIMIDINE 4 CARBOXYLIC ACID; CARBOXYLIC ACID DERIVATIVE; DIHYDROPYRIDINE DERIVATIVE; DIHYDROXYFUMARIC ACID; HYDROCHLORIC ACID; PYRIMIDINONE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; METHODOLOGY; POLYMERIZATION; STEREOCHEMISTRY;

EID: 3142693351     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2004.06.028     Document Type: Article

References (15)

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11. 13C NMR are complex due to keto-enol tautomers and the ketone hydrate. NMR spectra confirming these structures are provided in the Supplementary materials. The purified product is a single spot by TLC analysis. We recommend that fumarate reagent 3c be used directly after chromatographic purification, due to decomposition, which can reduce yields in the heterocycle formation. Compound 3c can be stored for several days in a -20°C freezer, with minimal decomposition
12. The yield was determined by quantitative HPLC by comparison with a known amount of a purified standard
13. 6) 164.3, 159.7, 159.5, 145.7, 139.4, 137.3, 128.6, 128.3 (two peaks), 82.6, 73.4, 27.9, 13.5, 10.0
14. The pyrimidinones could not be purified in good yield by silica-gel chromatography due to streaking of the products on the column
15. deposit@ccdc.cam.ac.uk) Crystallographic data (excluding structure factors) for the structure in this paper, have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 236303. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk)