著者

森田 岩男 津田 正己 黄瀬 正博 杉山 信

出版者

公益社団法人日本薬学会

雑誌

Chemical & pharmaceutical bulletin (ISSN:00092363)

巻号頁・発行日

vol.36, no.3, pp.1139-1142, 1988-03-25

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Attempts were made to improve the synthesis of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate (DHP-218), a new calcium antagonist. 2-Acetonyl-2-oxo-1,3,2-dioxaphosphosphorinane (5a), the key intermediate, was prepared from the allenylphosphonate (2) via the enaminophosphonate (4) in a good yield. Subsequently, the Knoevenagel condensation using 5a and the imine (6a) gave the benzylideneacetonylphosphonate (7a) in a good yield without the use of the Horner-Emons reaction. This condensation also gave good results for other acetonylphopshonates. The final step gave DHP-218 in a good yield through a modified Hantzsch synthesis with the use of a dehydrating agent. The overall yield was increased from 1.7% to 22%.