4-[N-methyl-N-(tetrahydropyran-4-yl)-aminomethyl]aniline dihydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[N-methyl-N-(tetrahydropyran-4-yl)-aminomethyl]aniline dihydrochloride
• 英文别名: 4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]aniline dihydrochloride；N-[(4-aminophenyl)methyl]-N-methyloxan-4-amine;hydrochloride
• 化学式: C₁₃H₂₀N₂O*2ClH
• 分子量: 293.236
• InChiKey: IDQRHFYVWMBCIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  38.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[N-methyl-N-(tetrahydropyran-4-yl)-aminomethyl]aniline dihydrochloride 、 在 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以139 g的产率得到7-{4-[2-(butoxy)ethoxy]phenyl}-N-(4-{[methyl(tetrahydro-2H-pyran-4-yl)amino]methyl}phenyl)-1-propyl-2,3-dihydro-1H-1-benzazepine-4-carboxamide
  参考文献：
  名称：

  实用的口服活性CCR5拮抗剂7- {4- [2-（丁氧基）-乙氧基]苯基} -N-（4-{[甲基（四氢-2 H-吡喃-4-基）氨基]甲基}的合成苯基）-1-丙基-2,3-二氢-1 H -1-苯并ze庚因-4-羧酰胺

  摘要：

  合成7- {4- [2-（丁氧基）乙氧基]苯基} -N-（4-{[甲基（四氢-2 H-吡喃-4-基）氨基]甲基}苯基）-1-的实用方法已开发出口服活性CCR5拮抗剂丙基2,3-二氢-1 H -1-苯并ze庚因-4-羧酰胺（8）。通过4-[（4-溴-2-甲酰基苯基）（）的酯化反应以高收率合成了7-溴-1-丙基-2,3-二氢-1 H -1-苯并ze庚因-4-羧酸甲酯（14a）。丙基）氨基]丁酸（13），然后在一个锅中与28％甲醇钠的碳酸二甲酯溶液作为溶剂进行分子内Claisen型反应。14a和1-溴-4-（2-丁氧基乙氧基）苯的Suzuki-Miyaura反应（10）然后水解和酰胺化得到8。建立了一种无需色谱纯化的廉价新方法。

  DOI：

  10.1021/op0497916
• 作为产物：
  描述：

  4-硝基苄胺 在 盐酸 、 tin(II) chloride dihydrate 、 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 生成 4-[N-methyl-N-(tetrahydropyran-4-yl)-aminomethyl]aniline dihydrochloride
  参考文献：
  名称：

  Process Development of 4-[N-Methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline Dihydrochloride:  A Key Intermediate for TAK-779, a Small-Molecule Nonpeptide CCR5 Antagonist

  摘要：

  A new and efficient synthesis of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline dihydrochloride, a key intermediate for the CCR5 antagonist TAK-779, is described. Reductive alkylation of methylamine with tetrahydro-4H-pyran-4-one followed by alkylation of N-methyl-N-(tetrahydropyran-4-yl)amine with 4-nitrobenzylbromide and reduction of N-(4-nitrobenzyl)-N-(tetrahydropyran-4-yl)amine results in a 78% isolated yield from the starting materials by a scalable method, using only commercially available reagents.

  DOI：

  10.1021/op010052o

文献信息

• Cyclic compounds and uses thereof
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06627651B1

  公开（公告）日：2003-09-30

  Compounds of general formula (1) R1—X1—W—X2—Z1—Z2—R2 or salts thereof, exhibiting preventive and therapeutic effects against HIV infectious diseases wherein R1 is an optionally substituted five- or six-membered ring group; X1 is a free valency or the like; W is a divalent group represented by, e. g., general formula (2) (wherein A and B are each an optionally substituted five- to seven-membered ring; E1 and E4 are each optionally substituted carbon or the like; E2 and E3 are each oxygen or the like; and a and b are each a single bond or a double bond); X2 is a divalent group constituting a straight chain moiety; Z1 is a divalent cyclic group or the like; Z2 is a free valency or the like; and R2 is optionally substituted amino or the like.

  一般公式（1）的化合物 R1—X1—W—X2—Z1—Z2—R2 或其盐，具有预防治疗HIV传染性疾病的作用，其中R1是可选地取代的五至六元环基团；X1是自由价电子或类似物；W是二价基团，例如，由一般公式（2）表示 （其中A和B各自是可选地取代的五至七元环；E1和E4各自是可选地取代的碳或类似物；E2和E3各自是氧或类似物；a和b各自是单键或双键）；X2是构成直链部分的二价基团；Z1是二价环状基团或类似物；Z2是自由价电子或类似物；R2是可选地取代的氨基或类似物。
• BENZAZEPINE DERIVATIVES, PROCESS FOR THE PREPARATION OF THE SAME AND USES THEREOF
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1186604A1

  公开（公告）日：2002-03-13

  Compounds of the general formula (I): or salts thereof, which exhibit CCR5 antagonism and exert preventive and therapeutic effects against HIV infections: wherein R1 is a 5- to 6-membered aromatic ring which bears a substituent represented by the general formula: R-Z1-X-Z2- (wherein R1 is hydrogen or optionally substituted hydrocarbyl; X is optionally substituted alkylene; and Z1 and Z2 are each a heteroatom) and may be further substituted, with R being optionally bonded to the aromatic ring to form another ring; Y is optionally substituted imino; and R2 and R3 are each optionally substituted aliphatic hydrocarbyl or an optionally substituted hetero-alicyclic group.

  具有一般公式(I)的化合物： 或其盐，具有CCR5拮抗作用，并对HIV感染具有预防和治疗作用：其中R1是一个5至6成员的芳香环，带有一个由一般公式表示的取代基：R-Z1-X-Z2-（其中R1是氢或可选地取代的碳氢基；X是可选地取代的亚烷基；Z1和Z2都是杂原子）并可进一步取代，R可可选地与芳香环结合形成另一个环；Y是可选地取代的亚胺；R2和R3各自是可选地取代的脂肪族碳氢化合物或一个可选地取代的杂环脂肪族基团。
• An Efficient and Practical Method for Highly Chemoselective Hydrogenation of Nitrobenzylamines to Aminobenzylamine Hydrochlorides
  作者：Chuanjie Cheng、Xinyan Wang、Lixin Xing、Bo Liu、Rui Zhu、Yuefei Hu

  DOI：10.1002/adsc.200600521

  日期：2007.7.2

  proved to be a very reliable modulator for adjusting the reactivity of palladium on carbon. Thus an efficient and practical method for the highly chemoselective hydrogenation of N,N-dialkylnitrobenzylamines to amino-N,N-dialkylbenzylamine hydrochlorides was established. The method features convenient performance, easy work-up and high efficiency.

  盐酸水溶液被证明是用于调节钯/碳反应性的非常可靠的调节剂。因此，建立了将N，N-二烷基硝基苄基胺高度化学选择性氢化成氨基-N，N-二烷基苄基胺盐酸盐的有效且实用的方法。该方法性能方便，后处理容易，效率高。
• Efficient synthesis of CCR5 antagonist, 2,3-dihydro-1-benzothiepine derivatives by improved intramolecular Claisen type reaction using dialkylcarbonate
  作者：Tomomi Ikemoto、Tatsuya Ito、Atsuko Nishiguchi、Kiminori Tomimatsu

  DOI：10.1016/j.tet.2004.09.039

  日期：2004.11

  The efficient synthesis of 2,3-dihydro-1-benzothiepine derivatives 4 has been developed. The intramolecular Claisen type reaction of the new products, 4-(o-formylphenylthio)butyrate 9, with alcoholate in dialkylcarbonate as a solvent afforded 4 in good yields. According to this new procedure, we have accomplished the practical preparation of CCR5 antagonist 1 as a candidate for oral HIV-1 therapy.

  已经开发了2，3-二氢-1-苯并噻庚因衍生物4的有效合成。新产物4-（邻甲酰基苯硫基）丁酸酯9与醇盐在碳酸二烷基酯中的分子内克莱森型反应以良好的收率得到4。根据这一新程序，我们已经完成了CCR5拮抗剂1的实际制备，可作为口服HIV-1治疗的候选药物。
• CYCLIC COMPOUNDS AND USES THEREOF
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1182195A1

  公开（公告）日：2002-02-27

  Compounds of general formula (1) or salts thereof, exhibiting preventive and therapeutic effects against HIV infectious diseases wherein R1 is an optionally substituted five- or six-membered ring group; X1 is a free valency or the like; W is a divalent group represented by, e. g., general formula (2) (wherein A and B are each an optionally substituted five-to seven-membered ring; E1 and E4 are each optionally substituted carbon or the like; E2 and E3 are each oxygen or the like; and a and b are each a single bond or a double bond); X2 is a divalent group constituting a straight chain moiety; Z1 is a divalent cyclic group or the like; Z2 is a free valency or the like; and R2 is optionally substituted amino or the like.

  通式(1)化合物 或其盐类，对 HIV 感染性疾病具有预防和治疗作用 其中 R1 是任选取代的五元或六元环基；X1 是游离价或类似物；W 是二价基团，如通式（2）所代表的二价基团。 (其中 A 和 B 分别为任选取代的五至七元环；E1 和 E4 分别为任选取代的碳或类似物；E2 和 E3 分别为氧或类似物；以及 a 和 b 分别为单键或双键）；X2 为构成直链分子的二价基团；Z1 为二价环状基团或类似物；Z2 为自由价或类似物；以及 R2 为任选取代的氨基或类似物。