Improved Synthesis of Methyl 2,6-Dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-doxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate (DHP-218)

• 森田 岩男

  Research Laboratories, Noppon Shinyaku Co., Ltd.,

• 津田 正己

  Research Laboratories, Noppon Shinyaku Co., Ltd.,

• 黄瀬 正博

  Research Laboratories, Noppon Shinyaku Co., Ltd.,

• 杉山 信

  Research Laboratories, Noppon Shinyaku Co., Ltd.,

抄録

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%.

収録刊行物

• Chemical & pharmaceutical bulletin

  Chemical & pharmaceutical bulletin 36 (3), 1139-1142, 1988-03-25

  公益社団法人日本薬学会

キーワード

• DHP-218
• calcium antagonist
• improved synthesis
• acetonylphosphonate
• allenylphosponate
• benzylideneacetonylphosphonate
• enaminophosphonate
• knoevenagel condensation
• Schiff base
• modified Hantzsch synthesis

詳細情報

• CRID: 1572261552365570688
• NII論文ID: 110003654778
• NII書誌ID: AA00602100
• ISSN: 00092363
• 本文言語コード: en
• データソース種別:
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