Development and Production of an Enantioselective Tetrahydroisoquinoline Synthesis Enabled by Continuous Cryogenic Lithium–Halogen Exchange

Author:

Cole Kevin P.1ORCID,Argentine Mark D.1,Conder Edward W.1,Vaid Radhe K.1,Feng Pengyao2,Jia Mo2,Huang Ping2,Liu Peng2,Sun Baoquan2,Tadayon Sam2,Zhu Cheng2,Zhu Ruiheng2

Affiliation:

1. Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, Indiana 46285, United States

2. Shanghai SynTheAll Pharmaceutical Co., Ltd. (STA), No. 13 Building, #90 Delin Road, WaiGaoQiao Free Trade Zone, Shanghai 200131, P.R. China

Publisher

American Chemical Society (ACS)

Subject

Organic Chemistry,Physical and Theoretical Chemistry

Reference25 articles.

1. aBeadle, C. D.; Coates, D. A.; Hao, J.; Krushinski, J. H., Jr.; Reinhard, M. R.; Schaus, J. M.; Wolfangel, C. D. 3,4-Dihydroisoquinolin-2(1H)-yl Compounds. WO 2014193781 A1, 2014.

2. bStephenson, G. A Crystalline Form of 2-(2,6-Dichlorophenyl)-1-[(1S,3R)-3-(hydroxymethyl)-5-(3-hydroxy-3-methylbutyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanone for the Treatment of Parkinson’s Disease. WO 2017070068 A1, 2017.

3. Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor

4. A Study of LY3154207 in Participants with Dementia Due to Lewy Body Dementia (LBD) Associated with Idiopathic Parkinson’s Disease (PD) or Dementia with Lewy Bodies (DLB) (PRESENCE). ClincalTrials.gov (U.S. National Institutes of Health, Bethesda, MD), October 10, 2017. https://clinicaltrials.gov/ct2/show/NCT03305809?intr=LY3154207 (accessed 2020-01-18).

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