Concise Synthesis of a Selective α1-Adrenoceptor Antagonist

Autor:	Terrence J. Connolly, Jiang Zhu, Michael Allen Matchett, Sunil Sukhtankar, Patrick Finbar Mcgarry
Rok vydání:	2006
Předmět:	Active ingredient Amidine chemistry.chemical_compound Reaction calorimeter Chemistry Organic Chemistry Functional group Iminium Organic chemistry Selective catalytic reduction Physical and Theoretical Chemistry Decomposition Dimethylacetamide
Zdroj:	Organic Process Research & Development. 10:391-397
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op050122h
Popis:	An efficient synthesis of an adrenoceptor antagonist has been developed and demonstrated in a pilot plant. A linear synthesis that relied on a catalytic reduction of a rather insoluble nitroaromatic proved to be a viable route. The active pharmaceutical ingredient (API) that contained an amidine functional group was generated from the amino-containing precursor by activation of dimethylacetamide (DMA) with phosphorus oxychloride (POCl3). The reaction between DMA and POCl3 was studied using ReactIR and was found to be a fast but not instantaneous reaction. The iminium salt generated from DMA and POCl3 had acceptable stability to allow for its use on a pilot-plant scale; however, a trend towards decomposition was revealed on the basis of in situ FTIR data. Formation of the complex was evaluated in a reaction calorimeter (RC-1), and the stability of the complex was probed with an Advanced Reactive System Screening Tool (ARSST).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::9d428495d6fe1f02b0b34ac8e527dc6c https://doi.org/10.1021/op050122h Zobrazit plný text záznamu