(6-Chloro-1,2,3,4-tetrahydroquinolin-3-yl)methanol | 1017328-80-1

• 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-1,2,3,4-tetrahydroquinolin-3-yl)methanol
• CAS: 1017328-80-1
• 化学式: C₁₀H₁₂ClNO
• 分子量: 197.664
• InChiKey: HGZOCPAVWMJJFT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (6-Chloro-1,2,3,4-tetrahydroquinolin-3-yl)methanol 、 二甲胺 以 水 、 二甲基亚砜 为溶剂， 反应 5.0h， 以25.1 kg的产率得到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
• 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 、 乙酸酐 、 乙酸乙酯 为溶剂， 反应 9.5h， 生成 (6-Chloro-1,2,3,4-tetrahydroquinolin-3-yl)methanol
  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

• Process for the Preparation of an Amorphous, Peptide-like Diabetes Drug: Approach to a Chromatography-Free Process
  作者：Yasuhiro Sawai、Taihei Yamane、Motoki Ikeuchi、Shinji Kawaguchi、Masatoshi Yamada、Mitsuhisa Yamano

  DOI：10.1021/op100084r

  日期：2010.9.17

  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.