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Uprifosbuvir (MK-3682) 的制造工艺开发：制备倒数第二个 2'-脱氧-α-2'-氯-β-2'-甲基尿苷的绿色可持续工艺
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2022-08-16 , DOI: 10.1021/acs.oprd.2c00191
Peter E. Maligres 1 , Feng Peng 1 , Ralph Calabria 1 , Louis-Charles Campeau 1 , Wenyong Chen 1 , Peter G. Dormer 1 , Meredith Green 1 , Cyndi Qixin He 1 , Alan M. Hyde 1 , Artis Klapars 1 , Mona Utne Larsen 1 , John Limanto 1 , Guiquan Liu 2 , Yizhou Liu 1 , Aaron Moment 1 , Timothy Nowak 1 , Rebecca T. Ruck 1 , Michael Shevlin 1 , Zhiguo Jake Song 1 , Lushi Tan 1 , Weidong Tong 1 , Jacob H. Waldman 1 , Honglin Ye 2 , Ralph Zhao 1 , George Zhou 1 , Michael A. Zompa 1 , Susan L. Zultanski 1
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2022-08-16 , DOI: 10.1021/acs.oprd.2c00191
Peter E. Maligres 1 , Feng Peng 1 , Ralph Calabria 1 , Louis-Charles Campeau 1 , Wenyong Chen 1 , Peter G. Dormer 1 , Meredith Green 1 , Cyndi Qixin He 1 , Alan M. Hyde 1 , Artis Klapars 1 , Mona Utne Larsen 1 , John Limanto 1 , Guiquan Liu 2 , Yizhou Liu 1 , Aaron Moment 1 , Timothy Nowak 1 , Rebecca T. Ruck 1 , Michael Shevlin 1 , Zhiguo Jake Song 1 , Lushi Tan 1 , Weidong Tong 1 , Jacob H. Waldman 1 , Honglin Ye 2 , Ralph Zhao 1 , George Zhou 1 , Michael A. Zompa 1 , Susan L. Zultanski 1
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描述了一种从双新戊酰叔醇5a制备 Uprifosbuvir 中间体 2'-脱氧-α-2'-氯-β-2'-甲基尿苷 ( 1 ) 的简单有效的方法。关键发现是一种由 HCl 作为添加剂催化的新型 BSA 促进的脱水尿苷形成，以及一种更温和、安全的 Me 2 SiCl 2促进脱水尿苷的氯化反应。这些发现共同促成了针对化合物1的稳健过程的建立，这在工厂规模上得到了成功证明。
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更新日期：2022-08-16
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