6-chloro-3-(R)-[(N,N-dimethylamino)methyl]-1,2,3,4-tetrahydroquinoline | 246867-59-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6-chloro-3-(R)-[(N,N-dimethylamino)methyl]-1,2,3,4-tetrahydroquinoline
• 英文别名: 1-(6-chloro-1,2,3,4-tetrahydroquinolin-3-yl)-N,N-dimethylmethanamine；6-chloro-3-(N,N-dimethylamino)methyl-1,2,3,4-tetrahydroquinoline
• CAS: 246867-59-4
• 化学式: C₁₂H₁₇ClN₂
• 分子量: 224.733
• InChiKey: JUXRCKHOUDDWQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-4-methyl-2-(toluene-4-sulfonamido)pentanoic acid 、 6-chloro-3-(R)-[(N,N-dimethylamino)methyl]-1,2,3,4-tetrahydroquinoline 以 乙醇 为溶剂， 生成 1-[(3S)-6-chloro-1,2,3,4-tetrahydroquinolin-3-yl]-N,N-dimethylmethanamine N-[(4-methylphenyl)sulfonyl]-L-leucine salt 、 1-[(3R)-6-chloro-1,2,3,4-tetrahydroquinolin-3-yl]-N,N-dimethylmethanamine N-[(4-methylphenyl)sulfonyl]-L-leucine salt
  参考文献：
  名称：

  Process for the Preparation of an Amorphous, Peptide-like Diabetes Drug: Approach to a Chromatography-Free Process

  摘要：

  A manufacturing process suitable for large-scale production of the peptide-like amorphous compound N-((R)-1-{(3R)-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydroquinolin-1(2H)-yl}-3-(H-indo1-3-yl)-1-oxopropan-2-yl)-1-[(1-methyl-1H-indol-2-yl)carbon-yl]piperidine-4-carboxamide (1) as a drug for treating diabetes has been developed. The first kilogram quantities of 1 were prepared via a single-chromatography process that employed recyclable cation-exchange resin chromatography for an amorphous intermediate (2R)-2-amino-1-[(3R)-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydroquinolin-1(2H)-yl]-3-(1H-indol-3-y1)-propan-1-one (syn-3a). We have also developed a chromatography-free process that involves a combination purification of extraction of syn-3a with crystallization of syn-3a center dot 0.25H(3)PO(4)center dot 0.5H(2)O. The latter process afforded amorphous compound 1 with >98% purity by HPLC area analysis, the same quality as that provided by the former process.

  DOI：

  10.1021/op100084r
• 作为产物：
  描述：

  5-氯-2-硝基苯甲醛 在 sodium tetrahydroborate 、 sodium acetate 、 溶剂黄146 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙酸酐 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 14.5h， 生成 6-chloro-3-(R)-[(N,N-dimethylamino)methyl]-1,2,3,4-tetrahydroquinoline
  参考文献：
  名称：

  Process for the Preparation of an Amorphous, Peptide-like Diabetes Drug: Approach to a Chromatography-Free Process

  摘要：

  A manufacturing process suitable for large-scale production of the peptide-like amorphous compound N-((R)-1-{(3R)-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydroquinolin-1(2H)-yl}-3-(H-indo1-3-yl)-1-oxopropan-2-yl)-1-[(1-methyl-1H-indol-2-yl)carbon-yl]piperidine-4-carboxamide (1) as a drug for treating diabetes has been developed. The first kilogram quantities of 1 were prepared via a single-chromatography process that employed recyclable cation-exchange resin chromatography for an amorphous intermediate (2R)-2-amino-1-[(3R)-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydroquinolin-1(2H)-yl]-3-(1H-indol-3-y1)-propan-1-one (syn-3a). We have also developed a chromatography-free process that involves a combination purification of extraction of syn-3a with crystallization of syn-3a center dot 0.25H(3)PO(4)center dot 0.5H(2)O. The latter process afforded amorphous compound 1 with >98% purity by HPLC area analysis, the same quality as that provided by the former process.

  DOI：

  10.1021/op100084r

文献信息

• Amine compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06329389B1

  公开（公告）日：2001-12-11

  The present invention provides a compound of the formula: wherein Ar represents an aromatic group which may be substituted; X represents methylene, S, SO, SO2 or CO; Y represents a spacer having a main chain of 2 to 5 atoms; n represents an integer of 1 to 5; i) R1 and R2 each represents a hydrogen atom or a lower alkyl which may be substituted, ii) R1 and R2 form, taken together with the adjacent nitrogen atom, a nitrogen-containing heterocyclic ring which may be substituted, or iii) R1 or R2 together with —(CH2)n—N═ form, bonded to a component atom of Ring B, a spiro-ring which may be substituted; Ring A represents an aromatic ring which may be substituted; Ring B represents a 4- to 7-membered nitrogen-containing non-aromatic ring which may be further substituted by alkyl or acyl, with a proviso that X represents S, SO, SO2 or CO when Ring A has as a substituent a group represented by the formula: —NHCOR11 where R11 represents alkyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl or a group represented by the formula: —NHR12 where R12 represents alkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, or a salt thereof; which has an excellent somatostatin receptor binding inhibition action.

  本发明提供了一种化合物，其化学式如下： 其中Ar代表可能被取代的芳香基团； X代表亚甲基、S、SO、SO2或CO； Y代表具有2到5个原子的主链的间隔物； n代表1到5的整数； i）R1和R2分别代表氢原子或可能被取代的较低烷基， ii）R1和R2与相邻的氮原子一起形成可能被取代的含氮杂环环，或 iii）R1或R2与—(CH2)n—N═一起形成，与环B的一个组分原子结合，可能被取代的螺环； 环A代表可能被取代的芳香环； 环B代表可能被烷基或酰基进一步取代的4到7成员的含氮非芳香环， 但有一个条件是，当环A具有由下式表示的基团作为取代基时： —NHCOR11 其中R11代表烷基、烷氧基烷基、烷硫基烷基、环烷基、环烷基烷基、芳基、芳基烷基或由下式表示的基团： —NHR12 其中R12代表烷基、环烷基、环烷基烷基、芳基或芳基烷基，或其盐；具有优异的生长抑素受体结合抑制作用。
• [EN] ARYL FUSED AZAPOLYCYCLIC COMPOUNDS<br/>[FR] COMPOSES AZAPOLYCYCLIQUES A FUSION ARYLE
  申请人：PFIZER PROD INC

  公开号：WO2001062736A1

  公开（公告）日：2001-08-30

  This invention is directed to compounds of formula (I) and their pharmaceutically acceptable salts, wherein R?1, R2, and R3¿ are as defined herein; intermediates for the synthesis of such compounds, pharmaceutical compositions containing such compounds; and methods of using such compounds in the treatment of neurological and psychological disorders.

  本发明涉及公式(I)化合物及其药学上可接受的盐，其中R1、R2和R3的定义如本文所述；合成此类化合物的中间体；含有此类化合物的制药组合物；以及使用此类化合物治疗神经系统和心理障碍的方法。
• AMINE DERIVATIVES
  申请人：Tadeka Chemical Industries, Ltd.

  公开号：EP1227090A1

  公开（公告）日：2002-07-31

  A compound of the formula:    wherein X and X' are the same or different, and each represents a hydrogen atom, a fluorine atom, a chlorine atom or an amino optionally having substituents, and at least one of X and X' represents a fluorine atom, a chlorine atom or an amino optionally having substituents; R1 and R2 represent a hydrogen atom or C1-6 alkyl optionally having substituents, or R1 and R2, together with the adjacent nitrogen atom, form a nitrogen-containing heterocyclic ring optionally having substituents; Y and Q are the same or different, and each represents a bond or a spacer having a main chain of 1 to 6 atoms; ... represents a single bond or a double bond; T1 and T2 are the same or different, and each represents C(R9) (R9 represents a hydrogen atom, a hydroxy or C1-6 alkyl) or N, when each of the adjacent ... is a single bond, and C when the adjacent ... is a double bond; and Ar represents an aromatic group optionally having substituents, a C3-9 cycloalkyl group optionally having substituents, a 3 to 9-membered saturated heterocyclic group optionally having substituents, a hydrogen atom or a halogen atom; provided that 6-chloro-3-(R,S)-(N,N-dimethylamino)methyl-1-[3-(indol-3-yl)-2-[(R)-(4-phenylpiperazin-1-yl)carbonylamino]propanoyl]-1,2,3,4-tetrahydroquinoline; 6-chloro-3-(R,S)-(N,N-dimethylamino)methyl-1-[3-(indol-3-yl)-2-[(R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidinocarbonylamino]propanoyl]-1,2,3,4-tetrahydroquinoline and 1-benzoyl-N-[(R)-2-[6-chloro-3-[(N,N-dimethylamino)methyl]-1,2,3,4-tetrahydroquinolin-1-yl]-1-[3-(indol-3-yl)propanoyl]-4-piperidinecarboxamide are excluded; a salt thereof or a prodrug thereof has an excellent somatostatin receptor binding inhibition action and is useful for preventing and/or treating diseases associated with somatostatin.

  式中的化合物 X和X'相同或不同，各自代表氢原子、氟原子、氯原子或可选具有取代基的氨基，且X和X'中至少有一个代表氟原子、氯原子或可选具有取代基的氨基； R1 和 R2 代表氢原子或任选具有取代基的 C1-6 烷基，或 R1 和 R2 与相邻的氮原子一起形成任选具有取代基的含氮杂环； Y 和 Q 相同或不同，各自代表主链为 1 至 6 个原子的键或间隔物； 代表单键或双键； T1 和 T2 相同或不同，当相邻......中的每一个为单键时，各自代表 C(R9)（R9 代表氢原子、羟基或 C1-6 烷基）或 N，当相邻......中的每一个为双键时，各自代表 C；以及 Ar 代表任选具有取代基的芳香基、任选具有取代基的 C3-9 环烷基、任选具有取代基的 3-9 元饱和杂环基、氢原子或卤素原子；条件是 6-氯-3-(R,S)-(N,N-二甲基氨基)甲基-1-[3-(吲哚-3-基)-2-[(R)-(4-苯基哌嗪-1-基)羰基氨基]丙酰基]-1,2,3,4-四氢喹啉；6-氯-3-(R,S)-(N,N-二甲基氨基)甲基-1-[3-(吲哚-3-基)-2-[(R)-4-(2-氧代-2,3-二氢-1H-苯并咪唑-1-基)哌啶甲酰氨基]丙酰基]-1,2,3,4-四氢喹啉不包括 1-苯甲酰基-N-[(R)-2-[6-氯-3-[(N,N-二甲基氨基)甲基]-1,2,3,4-四氢喹啉-1-基]-1-[3-(吲哚-3-基)丙酰基]-4-哌啶甲酰胺；其盐或其原药具有优异的抑制体生长抑素受体结合的作用，可用于预防和/或治疗与体生长抑素相关的疾病。
• ARYL FUSED AZAPOLYCYCLIC COMPOUNDS
  申请人：Pfizer Products Inc.

  公开号：EP1259489A1

  公开（公告）日：2002-11-27
• US6329389B1
  申请人：——

  公开号：US6329389B1

  公开（公告）日：2001-12-11