New Synthesis of Lumateperone Tosylate
- 1 January 2021
- journal article
- research article
- Published by The Japan Institute of Heterocyclic Chemistry in HETEROCYCLES
- Vol. 102 (11), 2197-2206
- https://doi.org/10.3987/com-21-14527
Abstract
A new and practical synthesis of lumateperone tosylate is developed. The intermediate, ethyl (4aS,9bR)-6-bromo-1,3,4,4a,5,9b-hexahydro-2H-pyrido-[4,3-b]indole-2-carboxylate (12), is prepared on kilograms scale in 31% overall yield and >99% ee. (6bR,10aS)-3-Methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline hydrochloride (16-HCl) is obtained through reductamination reaction, palladium catalyzed cyclization and ester hydrolysis in 60% yield over 3 steps and >98% purity. Lumateperone tosylate is produced on 20 g scale in 65% yield over 2 steps and >99% purity (HPLC). Purification methods of the intermediates and the final product involved in the route are developed.Keywords
This publication has 5 references indexed in Scilit:
- An evaluation of lumateperone tosylate for the treatment of schizophreniaExpert Opinion on Pharmacotherapy, 2019
- Lumateperone: a new treatment approach for neuropsychiatric disordersDrugs of Today, 2018
- Discovery of a Tetracyclic Quinoxaline Derivative as a Potent and Orally Active Multifunctional Drug Candidate for the Treatment of Neuropsychiatric and Neurological DisordersJournal of Medicinal Chemistry, 2014
- Radical Cage Effects in the Photochemical Degradation of Polymers: Effect of Radical Size and Mass on the Cage Recombination Efficiency of Radical Cage Pairs Generated Photochemically from the (CpCH2CH2N(CH3)C(O)(CH2)nCH3)2Mo2(CO)6 (n = 3, 8, 18) ComplexesJournal of the American Chemical Society, 2003
- Chain Length-Dependent Affinity of Helical Foldamers for a Rodlike GuestJournal of the American Chemical Society, 2001