2,4-二氟苯甲酰 | 158697-67-7

• 物质功能分类: 有机原料 - 酮类化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2,4-二氟苯甲酰
• 中文别名: 利培酮杂质H
• 英文名称: DES(6-fluoro-1,2-benzoxazole)-2,4-difluorobenzoyl risperidone
• 英文别名: 3-[2-[4-(2,4-difluorobenzoyl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one
• CAS: 158697-67-7
• 化学式: C₂₃H₂₇F₂N₃O₂
• 分子量: 415.5
• InChiKey: VVQWCIXBRCHDBW-UHFFFAOYSA-N

物化性质

• 熔点：
  466-467 °C
• 沸点：
  543.6±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  53
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,4-二氟苯甲酰 以64的产率得到3-[2-[4-[(2,4-difluorophenyl)-(hydroxyimino)-methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  Arch. Pharmacal. Res. 2005, 28, 1019-1022

  摘要：

  DOI：
• 作为产物：
  描述：

  2,4-二氟苯基-4-哌啶基甲酮 、 (2-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-3-yl)-acetaldehyde 在 2,4-二氟苯基-4-哌啶基甲酮 作用下， 以88的产率得到2,4-二氟苯甲酰
  参考文献：
  名称：

  Arch. Pharmacal. Res. 2005, 28, 1019-1022

  摘要：

  DOI：

文献信息

• Process for the preparation of 3-{2-'4- (6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl!ethyl}-6,7,8,9-tetrahydro-2-methyl-4h-pyrido'1,2-methyl-4h-pyrido',2-a!pyrimidin-4-one
  申请人：Pongo Laszlo

  公开号：US20050004141A1

  公开（公告）日：2005-01-06

  The invention relates to a process for the preparation of 3-2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl}-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one of the Formula (I), and pharmaceutically acceptable acid addition salts thereof by subjecting the oxime of the Formula (II), to ring-closure in the presence of an alkali hydroxide, alkali carbonate or alkali-C 1-4 alkoxide in an inert organic solvent, converting the base of the Formula I thus obtained into an acid addition salt or setting free the base of the Formula I from an acid addition salt thereof which comprises reacting a halogen derivative of the general Formula (XIV), (wherein Hal is halogen) with piperidine oxime derivative of the Formula (V), or an acid addition salt thereof in the presence of a base, and using by the ring-closure of the oxime of the Formula II formed a C 1-4 -alkanol as inert solvent. The process of the present invention enables the economical preparation of a product having a purity suitable for pharmaceutical purposes.

  本发明涉及一种制备公式（I）中的3-2-[4-(6-氟-1,2-苯并异噁唑-3-基)-1-哌啶基]乙基}-6,7,8,9-四氢-2-甲基-4H-吡啶[1,2-a]嘧啶-4-酮及其药学上可接受的酸加成盐的过程，包括在惰性有机溶剂中在碱性氢氧化物、碱性碳酸盐或碱性C1-4烷氧化物的存在下，使公式（II）的肟在环闭合的情况下，将公式I的碱转化为酸加成盐或从其酸加成盐中释放出公式I的碱。其中，该过程包括在碱的存在下，使用公式（XIV）的卤代衍生物（其中Hal是卤素）与公式（V）的哌啶肟衍生物或其酸加成盐在惰性溶剂C1-4-烷醇中进行肟的环闭合。本发明的过程能够经济地制备出适用于药物用途的纯度合适的产物。
• Process for the preparation of 3-{2-′4- (6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyllethyl}-6,7,8,9-tetrahydro-2-methyl-4h-pyrido′1,2-methyl-4h-pyrido′,2-a!pyrimidin-4-one
  申请人：EGIS Gyógyszergyár Rt.

  公开号：US07307168B2

  公开（公告）日：2007-12-11

  The invention relates to a process for the preparation of 3-2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl}-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one of the Formula (I), and pharmaceutically acceptable acid addition salts thereof by subjecting the oxime of the Formula (II), to ring-closure in the presence of an alkali hydroxide, alkali carbonate or alkali-C1-4 alkoxide in an inert organic solvent, converting the base of the Formula I thus obtained into an acid addition salt or setting free the base of the Formula I from an acid addition salt thereof which comprises reacting a halogen derivative of the general Formula (XIV), (wherein Hal is halogen) with piperidine oxime derivative of the Formula (V), or an acid addition salt thereof in the presence of a base, and using by the ring-closure of the oxime of the Formula II formed a C1-4-alkanol as inert solvent. The process of the present invention enables the economical preparation of a product having a purity suitable for pharmaceutical purposes.

  本发明涉及一种制备式（I）的3-2-[4-(6-氟-1,2-苯并异噁唑-3-基)-1-哌啶基]乙基}-6,7,8,9-四氢-2-甲基-4H-吡啶[1,2-a]嘧啶-4-酮及其药学上可接受的酸加盐物的方法。该方法通过在惰性有机溶剂中，在碱性氢氧化物、碱性碳酸盐或碱性C1-4醇酸酸盐的存在下，使式（II）的肟转化为环闭合，将所得的式（I）的碱转化为酸加盐物或从其中释放出式（I）的碱加盐物，包括在碱的存在下，用式（V）的哌啶肟衍生物或其酸加盐物与通式（XIV）的卤代衍生物（其中Hal是卤素）反应，并使用C1-4醇作为惰性溶剂来进行肟的环闭合。本发明的方法使得经济地制备出适用于制药目的的纯度合适的产品。
• IMPROVED PROCESS FOR THE PREPARATION OF 3-(2-'4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)-1-PIPERIDINYL/ETHYL)-6,7,8,9-TETRAHYDRO-2-METHYL-4H-PYRIDO'1,2-A/PYRIMIDIN-4-ONE
  申请人：Egis Gyogyszergyar Rt.

  公开号：EP1461338A1

  公开（公告）日：2004-09-29
• IMPROVED PROCESS FOR THE PREPARATION OF 3-(2-(4-(6-FLUORO-1,2-BENZISOXAZOL-3-YL)-1-PIPERIDINYL)ETHYL)-6,7,8,9-TETRAHYDRO-2-METHYL-4H-PYRIDO(1,2-A)PYRIMIDIN-4-ONE
  申请人：EGIS Gyógyszergyár Nyrt

  公开号：EP1461338B1

  公开（公告）日：2007-05-02
• PROCESS FOR MAKING RISPERIDONE AND INTERMEDIATES THEREFOR
  申请人：Slanina Pavel

  公开号：US20080262227A1

  公开（公告）日：2008-10-23

  The formation of risperidone is enhanced by the use of enriched Z-isomer oxime intermediate(s) of formula (3) or (7). The oxime(s) can be isomerically enriched by a variety of techniques including the use of the novel acetic acid salt thereof, which affords, inter alia, resolution of the isomers and/or by heat conversion.