9H-fluoren-9-ylmethyl N-[(2R)-1-[(3R)-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydro-2H-quinolin-1-yl]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate | 1239474-82-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 9H-fluoren-9-ylmethyl N-[(2R)-1-[(3R)-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydro-2H-quinolin-1-yl]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate
• CAS: 1239474-82-8
• 化学式: C₃₈H₃₇ClN₄O₃
• 分子量: 633.19
• InChiKey: KCKLHYOUVMSHIL-CGDLVVIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  46
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  77.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  哌啶 、 9H-fluoren-9-ylmethyl N-[(2R)-1-[(3R)-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydro-2H-quinolin-1-yl]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate 以 甲醇 为溶剂， 反应 16.5h， 以1.88 kg的产率得到(2R)-2-amino-1-[(3R)-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydroquinolin-1(2H)-yl]-3-(1H-indol-3-yl)propan-1-one
  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：

  1-[6-chloro-1,2,3,4-tetrahydroquinolin-3-yl]-N,N-dimethylmethanamine N-[(4-methylphenyl)sulfonyl]-D-leucine salt 在 草酰氯 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.5h， 生成 9H-fluoren-9-ylmethyl N-[(2R)-1-[(3R)-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydro-2H-quinolin-1-yl]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate
  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

• US6329389B1
  申请人：——

  公开号：US6329389B1

  公开（公告）日：2001-12-11
• 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.