有哪些信誉好的足球投注网站synthesis of 9,9′-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6h-purin-6-one, an impurity of acyclovir合成的9,9u2032-(1,2-ethanediylbis(甲醛)]bis-2-amino-1,9-dihydro-6h-purin-6-one,阿昔洛韦的杂质.pdfVIP
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synthesis of 9,9′-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6h-purin-6-one, an impurity of acyclovir合成的9,9u2032-(1,2-ethanediylbis(甲醛)]bis-2-amino-1,9-dihydro-6h-purin-6-one,阿昔洛韦的杂质
Molecules 2012, 17, 8735-8741; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis of 9,9′-[1,2-Ethanediylbis(oxymethylene)]bis-2-amino- 1,9-dihydro-6H-purin-6-one, an Impurity of Acyclovir Rosa M. Suárez 1, Maria Paz Matía 1, José Luis Novella 1, Andres Molina 2, Antonio Cosme 2, Juan José Vaquero 3 and Julio Alvarez-Builla 3,* 1 Fine Chemicals Pilot Plant Facility, University of Alcalá, 28871 Alcalá de Henares, Madrid, Spain 2 Department of Research and Development, Química Sintética S. A., c./Dulcinea s/n, 28805 Alcala de Henares, Madrid, Spain 3 Department of Organic Chemistry, University of Alcalá, 28871 Alcalá de Henares, Madrid, Spain * Author to whom correspondence should be addressed; E-Mail: julio.alvarez@uah.es; Tel.: +34-91-885-4606; Fax: +34-91-885-4686. Received: 16 June 2012; in revised form: 13 July 2012 / Accepted: 16 July 2012 / Published: 25 July 2012 Abstract: The synthesis of 9,9-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro- 6H-purin-6-one, a minor impurity of acyclovir, is described. Starting with commercial N-(9-acetyl-6-oxo-1H-purin-2-yl)acetamide, the process uses an acid catalysed phase transfer catalysis (PTC) process to produce the selective alkylation at the 9 position of the guanine ring. Keywords: nucleosides; acyclovir; drug impurities; phase transfer catalysis 1. Introduction Drug impurities, called in the literature related substances in an active pharmaceutical ingre
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