NEW SYNTHETIC ROUTE TO (1S)-4,5-DIMETHOXY-1-[( METHYLAMINO) METHYL] BENZOCYCLOBUTANE, A KEY INTERMEDIATE OF IVABRADINE
文献类型：期刊论文
| 作者 | Liu, Xin1; Liu, Yu1,2; He, Huili1; Cai, Zhan1; Yang, Yushe1
|
| 刊名 | SYNTHETIC COMMUNICATIONS
 |
| 出版日期 | 2014-02-16 |
| 卷号 | 44期号:4页码:451-456 |
| 关键词 | Benzocyclobutane ivabradine reduction resolution |
| ISSN号 | 0039-7911 |
| DOI | 10.1080/00397911.2012.686081 |
| 文献子类 | Article |
| 英文摘要 | An efficient process for the preparation of (1S)-4,5-dimethoxy-1-[(methylamino)methyl] benzocyclobutane (S)-3 as ivabradine intermediate, which was obtained in 56% yield, is described. The salient feature of this process is the racemization of the undesired (1R)-4,5-dimethoxy-1,2-dihydrocyclobutabenzene-1-carboxylic acid (R)-12, and the overall yield of (S)-12 was improved to 70% by three resolutions of the racemized acid with R-()-phenylethanamine. The reduction of amide (S)-13 was achieved with NaBH4-I-2 in refluxing tetrahydrofuran, giving the corresponding amine (S)-3 in 90% yield. The improved synthetic route described herein is cost-efficient, environmentally friendly and feasibile for scale-up production. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resource(s): Full experimental and spectral details.] |
| 资助项目 | Nanjing C&O Pharmaceutical Technology (Holdings) Limited[00000000] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000329200500001 |
| 出版者 | TAYLOR & FRANCIS INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277182]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Yang, Yushe |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Shanghai Inst Pharmaceut Ind, Res Ctr Pharmaceut Proc, Novel Technol Ctr Pharmaceut Chem, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Xin,Liu, Yu,He, Huili,et al. NEW SYNTHETIC ROUTE TO (1S)-4,5-DIMETHOXY-1-[( METHYLAMINO) METHYL] BENZOCYCLOBUTANE, A KEY INTERMEDIATE OF IVABRADINE[J]. SYNTHETIC COMMUNICATIONS,2014,44(4):451-456. |
| APA | Liu, Xin,Liu, Yu,He, Huili,Cai, Zhan,&Yang, Yushe.(2014).NEW SYNTHETIC ROUTE TO (1S)-4,5-DIMETHOXY-1-[( METHYLAMINO) METHYL] BENZOCYCLOBUTANE, A KEY INTERMEDIATE OF IVABRADINE.SYNTHETIC COMMUNICATIONS,44(4),451-456. |
| MLA | Liu, Xin,et al."NEW SYNTHETIC ROUTE TO (1S)-4,5-DIMETHOXY-1-[( METHYLAMINO) METHYL] BENZOCYCLOBUTANE, A KEY INTERMEDIATE OF IVABRADINE".SYNTHETIC COMMUNICATIONS 44.4(2014):451-456. |
入库方式： OAI收割
来源：上海药物研究所
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