Scalable Process for Making 5,7-Dichlorotetrahydroisoquinoline-6-carboxylic Acid Using Methylene as the Protecting Group
文献类型：期刊论文
| 作者 | Xu, Wanbin1,2; Gong, Xudong3; Odilov, Abdullajon1,2; Hu, Tianwen2; Jiang, Xiangrui1 ; Zhu, Fuqiang3; Guo, Shuang3; Jiang, Dehui3; Wu, Mingjun3; Shen, Jingshan1,2
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| 刊名 | ORGANIC PROCESS RESEARCH & DEVELOPMENT
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| 出版日期 | 2021-11-19 |
| 卷号 | 25期号:11页码:2447-2452 |
| ISSN号 | 1083-6160 |
| 关键词 | 5,7-dichlorotetrahydroisoquinoline-6-carboxylic acid lifitegrast methylene atom utilization |
| DOI | 10.1021/acs.oprd.1c00229 |
| 通讯作者 | Zhu, Fuqiang(Fuqiang.zhu@topharman.cn) ; Shen, Jingshan(shenjingshan@simm.ac.cn) |
| 英文摘要 | The development of an industrially scalable synthetic route for 5,7-dichlorotetrahydroisoquinoline-6-carboxylic acid (1), a key starting material for lifitegrast, is described. This route includes the following features: (1) tetrahydroisoquinoline 19 was prepared in three steps from readily commercially available 3,5-dichlorobenzoyl chloride and 2-aminoethanol in a high total yield of 76%; (2) formaldehyde instead of triphenylmethyl chloride was employed in the protection of the secondary amine, resulting in much higher atom economy; (3) the target compound 1 was produced in an overall yield of 66% with an HPLC purity of 99% by area. |
| WOS关键词 | SODIUM-BOROHYDRIDE ; AMINALS ; ICAM-1 ; LIFITEGRAST ; ANTAGONIST ; DISCOVERY ; INSERTION ; STRATEGY ; POTENT ; AMINES |
| 资助项目 | Science and Technology Commission of Shanghai Municipality[19430750100] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000726748300009 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299244]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhu, Fuqiang; Shen, Jingshan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Topharman Shanghai Co Ltd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Wanbin,Gong, Xudong,Odilov, Abdullajon,et al. Scalable Process for Making 5,7-Dichlorotetrahydroisoquinoline-6-carboxylic Acid Using Methylene as the Protecting Group[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT,2021,25(11):2447-2452. |
| APA | Xu, Wanbin.,Gong, Xudong.,Odilov, Abdullajon.,Hu, Tianwen.,Jiang, Xiangrui.,...&Shen, Jingshan.(2021).Scalable Process for Making 5,7-Dichlorotetrahydroisoquinoline-6-carboxylic Acid Using Methylene as the Protecting Group.ORGANIC PROCESS RESEARCH & DEVELOPMENT,25(11),2447-2452. |
| MLA | Xu, Wanbin,et al."Scalable Process for Making 5,7-Dichlorotetrahydroisoquinoline-6-carboxylic Acid Using Methylene as the Protecting Group".ORGANIC PROCESS RESEARCH & DEVELOPMENT 25.11(2021):2447-2452. |
入库方式： OAI收割
来源：上海药物研究所
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