1-(4-isobutoxybenzyl)urea

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(4-isobutoxybenzyl)urea
• 英文别名: [4-(2-Methylpropoxy)phenyl]methylurea
• 化学式: C₁₂H₁₈N₂O₂
• 分子量: 222.287
• InChiKey: CCWITCJBWDGNQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-氟苄基)-1-甲基哌啶-4-胺 、 1-(4-isobutoxybenzyl)urea 反应 12.0h， 以83.1%的产率得到匹莫范色林
  参考文献：
  名称：

  Novel and Environmentally Friendly Synthesis of Pimavanserin (5-HT2A Receptor)

  摘要：

  使用4-异丁氧基苄胺作为关键起始材料，通过三种不同的路线，使用水作为溶剂，开发了pimavanserin的环保合成方法。这些反应具有易于操作、产物收率高以及使用水作为溶剂的优点。在分离产物时无需进行柱层析纯化。

  DOI：

  10.14233/ajchem.2019.21808
• 作为产物：
  描述：

  4-(2-甲基丙氧基)苯甲腈 在 ammonium hydroxide 、 氢气 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 20.0~150.0 ℃ 、500.01 kPa 条件下， 反应 5.0h， 生成 1-(4-isobutoxybenzyl)urea
  参考文献：
  名称：

  [EN] METHODS FOR PREPARING N-(4-FLUOROBENZYL)-N-(1-METHYLPIPERIDIN-4-YL)-N'-(4-(2-METHYLPROPYLOXY)PHENYLMETHYL)CARBAMIDE AND ITS TARTRATE SALT AND POLYMORPHIC FORM C
  [FR] PROCÉDÉS DE PRÉPARATION DE N-(4-FLUOROBENZYL)-N-(1-MÉTHYLPIPÉRIDIN-4-YL)-N'-(4-2-MÉTHYLPROPYLOXY)PHÉNYLMÉTHYL)CARBAMIDE, SON SEL DE TARTRATE ET SA FORME POLYMORPHE C

  摘要：

  公开号：

  WO2017015272A8

文献信息

• [EN] COMPOUNDS, SALTS THEREOF AND METHODS FOR TREATMENT OF DISEASES<br/>[FR] COMPOSÉS, SELS CORRESPONDANTS ET MÉTHODES POUR LE TRAITEMENT DE MALADIES
  申请人：ACADIA PHARM INC

  公开号：WO2019040107A1

  公开（公告）日：2019-02-28

  The present disclosure relates to compounds according to Formula (I), useful for treating diseases.

  本公开涉及按照式（I）的化合物，用于治疗疾病。
• [EN] SYNTHESIS OF N-(4-FLUOROBENZYL)-N-(1-METHYLPIPERIDIN-4-YL)-N'-(4-(2-METHYLPROPYLOXY)PHENYLMETHYL)CARBAMIDE AND ITS TARTRATE SALT AND CRYSTALLINE FORMS<br/>[FR] SYNTHESE DE N-(4-FLUOROBENZYL)-N-(1-METHYLPIPERIDIN-4-YL)-N'-(4-(2-METHYLPROPYLOXY)PHENYLMETHYL)CARBAMIDE, TARTRATE DE CE COMPOSE ET SES FORMES CRISTALLINES
  申请人：ACADIA PHARM INC

  公开号：WO2006037043A1

  公开（公告）日：2006-04-06

  Disclosed herein are methods for synthesizing N-(4-fluorobenzyl -N-(I-methylpiperidin­)4-yl)-N'-(442-methylpropyloxy)-phenylmethyl)carbamide, Formula (I). Also disclosed herein is the hemi­tartrate salt of N-(4-fluorobenzyl)-N-(I-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)­phenylmethyl)carbamide and methods for obtaining the salt. Further disclosed are various crystalline forms of N-(4-fluorobenzyl)-N-(I-methylpiperidin-4-yl)-N'-(4-(2-metylpropyloxy)-phenymethyl)carbamide and its hemi-tartrate salt including various polymorphs and solvates.

  本文披露了一种合成N-(4-氟苯甲基)-N-(1-甲基哌啶-4-基)-N'-(4-(2-甲基丙氧基)苯甲基)氨基甲酰胺（公式I）的方法。本文还披露了N-(4-氟苯甲基)-N-(1-甲基哌啶-4-基)-N'-(4-(2-甲基丙氧基)苯甲基)氨基甲酰胺的半酒石酸盐和获得该盐的方法。此外，本文还披露了N-(4-氟苯甲基)-N-(1-甲基哌啶-4-基)-N'-(4-(2-甲基丙氧基)苯甲基)氨基甲酰胺及其半酒石酸盐的各种晶体形式，包括各种多晶形和溶剂合物。
• Methods for preparing N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide and its tartrate salt and polymorphic form C
  申请人：ACADIA PHARMACEUTICALS INC.

  公开号：US10597363B2

  公开（公告）日：2020-03-24

  Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is —ORi or —NR2aR2b; R3 is hydrogen or substituted or unsubstituted heteroalicyclyl, R4 is substituted or unsubstituted aralkyl; X is —OR22 or —NR23R24; (wherein R22 is hydrogen or substituted or unsubstituted C1-6alkyl and one of R23 and R24 is hydrogen and the other is hydrogen or N-methylpiperidin-4-yl); and R21 is —OCH2CH(CH3)2 or F; Also disclosed herein is the tartrate salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt.

  本发明公开了获得N-(4-氟苄基)-N-(1-甲基哌啶-4-基)-N′-(4-(2-甲基丙氧基)苯基甲基)碳酰胺(匹马色林)的方法，包括将符合式(A)的中间体或其盐与符合式B的中间体或其盐接触生成匹马色林或其盐的步骤 其中Y是-ORi或-NR2aR2b；R3 是氢或取代或未取代的杂环烷基，R4 是取代或未取代的芳烷基；X 是-OR22 或-NR23R24；（其中 R22 是氢或取代或未取代的 C1-6 烷基，R23 和 R24 中的一个是氢，另一个是氢或 N-甲基哌啶-4-基）；本文还公开了N-(4-氟苄基)-N-(1-甲基哌啶-4-基)-N′-(4-(2-甲基丙氧基)苯基甲基)甲酰胺的酒石酸盐和获得该盐的方法。
• Methods for preparing N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl)carbamide and its tartrate salt and polymorphic form
  申请人：ACADIA Pharmaceuticals Inc.

  公开号：US10981870B2

  公开（公告）日：2021-04-20

  Disclosed herein are methods for obtaining N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide (pimavanserin) comprising the step of contacting an intermediate according to Formula (A) or a salt thereof, with an intermediate Formula B, or a salt thereof, to produce pimavanserin or a salt thereof wherein Y is —ORi or —NR2aR2b; R3 is hydrogen or substituted or unsubstituted heteroalicyclyl, R4 is substituted or unsubstituted aralkyl; X is —OR22 or —NR23R24; (wherein R22 is hydrogen or substituted or unsubstituted C1-6alkyl and one of R23 and R24 is hydrogen and the other is hydrogen or N-methylpiperidin-4-yl); and R21 is —OCH2CH(CH3)2 or F; Also disclosed herein is the tartrate salt of N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-(2-methylpropyloxy)phenylmethyl) carbamide and methods for obtaining the salt.

  本发明公开了获得N-(4-氟苄基)-N-(1-甲基哌啶-4-基)-N′-(4-(2-甲基丙氧基)苯基甲基)碳酰胺(匹马色林)的方法，包括将符合式(A)的中间体或其盐与符合式B的中间体或其盐接触生成匹马色林或其盐的步骤 其中Y是-ORi或-NR2aR2b；R3 是氢或取代或未取代的杂环烷基，R4 是取代或未取代的芳烷基；X 是-OR22 或-NR23R24；（其中 R22 是氢或取代或未取代的 C1-6 烷基，R23 和 R24 中的一个是氢，另一个是氢或 N-甲基哌啶-4-基）；本文还公开了N-(4-氟苄基)-N-(1-甲基哌啶-4-基)-N′-(4-(2-甲基丙氧基)苯基甲基)甲酰胺的酒石酸盐和获得该盐的方法。
• METHODS FOR PREPARING N-(4-FLUOROBENZYL)-N-(1-METHYLPIPERIDIN-4-YL)-N'-(4-(2-METHYLPROPYLOXY)PHENYLMETHYL)CARBAMIDE AND ITS TARTRATE SALT AND POLYMORPHIC FORM C
  申请人：Acadia Pharmaceuticals Inc.

  公开号：EP3325444B1

  公开（公告）日：2021-07-07