制造idelalisib的一种新策略：控制对映体的形成。
A novel strategy for the manufacture of idelalisib: controlling the formation of an enantiomer.
作者信息
Mekala Nagaraju, Buddepu Srinivasa Rao, Dehury Sanjay K, Moturu Krishna Murthy V R, Indukuri Sunil Kumar V, Vasireddi Umamaheswara Rao, Parimi Atchuta R
机构信息
Oncology Division, Process Development Laboratories, Laurus Laboratories Limited ICICI Knowledge Park, Turkapally, Shameerpet Hyderabad-500 078 Telangana India
Department of Organic Chemistry, Food, Drugs & Water, School of Chemistry, Andhra University Visakhapatnam-530 003 Andhra Pradesh India.
出版信息
RSC Adv. 2018 Apr 27;8(28):15863-15869. doi: 10.1039/c8ra00407b. eCollection 2018 Apr 23.
A novel and scalable synthesis of 5-fluoro-3-phenyl-2-[(1)-1-(9-purin-6-ylamino)propyl]-4(3)-quinazolinone, idelalisib 1, has been developed. This strategy controls the desfluoro impurity of 13 during reduction of nitro intermediate 4, and also arrests the formation of the enantiomer during cyclisation of diamide 17, without affecting the neighbouring chiral centre. This process is demonstrated on a larger scale in the laboratory and achieved good chemical and chiral purities coupled with good yields.
已开发出一种新颖且可扩展的合成5-氟-3-苯基-2-[(1)-1-(9-嘌呤-6-基氨基)丙基]-4(3)-喹唑啉酮（idelalisib 1）的方法。该策略在硝基中间体4还原过程中控制了13的脱氟杂质，并且在二酰胺17环化过程中阻止了对映体的形成，同时不影响相邻的手性中心。该过程在实验室中进行了更大规模的验证，获得了良好的化学纯度和手性纯度以及良好的产率。
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