Development and Kilogram-Scale Synthesis of a D2/5-HT2A Receptor Dual Antagonist (±)-SIPI 6360

Xiao Wen Chen, Yu Liu, Xun Qi Jin, Yuan Yuan Sun, Shun Lin Gu, Lei Fu*, Jian Qi Li

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


The kilogram-scale synthesis of a D2/5-HT2A receptor dual antagonist (±)-SIPI 6360 was developed as an alternative treatment for schizophrenia. Specifically, three conditions were modified and optimized, including the Vilsmeier conditions, to prepare quinoline 3. In addition, the palladium-catalyzed hydrogenation was modified to synthesize dihydroquinolin-2(1H)-one 5, and the reduction of β-chloroamide was altered to form 3-chloropropanamine 8. Ultimately these improvements led to the preparation of a 1.5 kg of (±)-SIPI 6360 batch in eight steps with an overall yield of 34% and purity of 99.8%.

Original languageEnglish
Pages (from-to)1662-1667
Number of pages6
JournalOrganic Process Research and Development
Issue number9
Publication statusPublished - 16 Sept 2016
Externally publishedYes

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