POLYMORPHIC FORM OF 4-[3-(4-CYCLOPROPANECARBONYL-PIPERAZINE-1-CARBONYL)-4-FLUORO-BENZYL]-2H-PHTHALAZIN-1-ONE

• Main Authors: ASHWORTH IAN WOODWARD, LAFFAN DAVID DERMOT PATRICK, MULLHOLLAND KEITH RAYMOND, JONES MARTIN FRANCIS, MENEAR KEITH ALLAN, PITTAM JOHN DAVID, OTTRIDGE ANTHONY PETER, HALLETT MICHAEL RAYMOND, CHERRYMAN JANETTE HELEN, LONDESBROUGH DEREK JOHN
• Format: Patent
• Language: English; Japanese
• Published: 22.01.2015
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

PROBLEM TO BE SOLVED: To provide a novel production method of a compound useful as an inhibitor of PARP which is an enzyme related to signal transduction of DNA damage.SOLUTION: In a production method of a compound represented by a formula A, 2-carboxybenzaldehyde is used as a starting material, and (a) diethyl (3-oxo-1,3-dihydro-2-benzofuran-1-yl)phosphonate, (b) 2-fluoro-5-[(E/Z)-(3-oxo-2-benzofuran-1(3H)-ylidene)methyl]benzonitrile, (c) 2-fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzonitrile, and (d)2-fluoro-5-(4-oxo-3,4-dihydro-phthalazin-1-ylmethyl)-benzoic acid are synthetic intermediates. 【課題】ＤＮＡ損傷のシグナル伝達に関係する酵素ＰＡＲＰの阻害剤として有用な化合物の新規製造方法の提供。【解決手段】記Ａで表される化合物の製造方法であって、2-カルボキシベンズアルデヒドを出発原料として、(a)ジエチル(3-オキソ-1,3-ジヒドロ-2-ベンゾフラン-1-イル)ホスホネート、(b)2-フルオロ-5-[(E/Z)-(3-オキソ-2-ベンゾフラン-1(3H)-イリデン)メチル]ベンゾニトリル、(c)2-フルオロ-5-[(4-オキソ-3,4-ジヒドロフタラジン-1-イル)メチル]ベンゾニトリル、及び(d)2-フルオロ-5-(4-オキソ-3,4-ジヒドロ-フタラジン-1-イルメチル)-安息香酸をそれぞれ合成中間体として経由する製造方法。【選択図】なし