Synthesis of 2,3-Disubstituted 4-Ethoxycarbonyl-β-carbolin-1-ones: Application to the Synthesis of SL651498 and Its Analogue

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Jul 9

PMID 32637839

Authors

Ryoya Miura

Shinsuke Goto

Takahide Hashimoto

Iwao Hachiya

Affiliations

Soon will be listed here.

Abstract

Synthesis of 2,3-disubstituted 4-ethoxycarbonyl-β-carbolin-1-ones is developed using palladium-catalyzed intramolecular amination of 3-amino-4-(2-bromophenyl)-2-pyridones prepared by the conjugate addition reaction of diethyl 2-aminomalonate to alkynyl imines. The method was applied to the total syntheses of SL651498 exhibiting anxiolytic activity and its analogue.

References

Madhavachary R, Naveen N, Wang Y, Wang Q, Konstantinidou M, Domling A . β-Carbolinone Analogues from the Ugi Silver Mine. European J Org Chem. 2019; 2018(24):3139-3143. PMC: 6706090. DOI: 10.1002/ejoc.201800557. View

Fillery S, Gregson C, Guerot C . Expeditious Access to Functionalized Tricyclic Pyrrolo-Pyridones via Tandem or Sequential C-N/C-C Bond Formations. Org Lett. 2019; 21(22):9128-9132. DOI: 10.1021/acs.orglett.9b03514. View

Han H, Yang S, Xia J . Pd/Cu Cocatalyzed Oxidative Tandem C-H Aminocarbonylation and Dehydrogenation of Tryptamines: Synthesis of Carbolinones. J Org Chem. 2019; 84(6):3357-3369. DOI: 10.1021/acs.joc.8b03266. View

Larsen L, Moore R, Patterson G . beta-Carbolines from the blue-green alga Dichothrix baueriana. J Nat Prod. 1994; 57(3):419-21. DOI: 10.1021/np50105a018. View

Griebel G, Perrault G, Simiand J, Cohen C, Granger P, Depoortere H . SL651498, a GABAA receptor agonist with subtype-selective efficacy, as a potential treatment for generalized anxiety disorder and muscle spasms. CNS Drug Rev. 2003; 9(1):3-20. PMC: 6741675. DOI: 10.1111/j.1527-3458.2003.tb00241.x. View

Sangu K, Fuchibe K, Akiyama T . A novel approach to 2-arylated quinolines: electrocyclization of alkynyl imines via vinylidene complexes. Org Lett. 2004; 6(3):353-5. DOI: 10.1021/ol036190a. View

Morri A, Thummala Y, Doddi V . The Dual Role of 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) in the Synthesis of Terminal Aryl- and Styryl-Acetylenes via Umpolung Reactivity. Org Lett. 2015; 17(18):4640-3. DOI: 10.1021/acs.orglett.5b02398. View

Wang S, Dong Y, Wang X, Hu X, Liu J, Hu Y . 3-Aryl beta-carbolin-1-ones as a new class of potent inhibitors of tumor cell proliferation: synthesis and biological evaluation. Org Biomol Chem. 2005; 3(5):911-6. DOI: 10.1039/b412921k. View

Jiao P, Nakashima D, Yamamoto H . Enantioselective 1,3-dipolar cycloaddition of nitrones with ethyl vinyl ether: the difference between Brønsted and Lewis acid catalysis. Angew Chem Int Ed Engl. 2008; 47(13):2411-3. DOI: 10.1002/anie.200705314. View

10.

Shi Z, Cui Y, Jiao N . Synthesis of beta- and gamma-carbolinones via Pd-catalyzed direct dehydrogenative annulation (DDA) of indole-carboxamides with alkynes using air as the oxidant. Org Lett. 2010; 12(13):2908-11. DOI: 10.1021/ol1007839. View

11.

Tulichala R, Swamy K . Reactivity of alkynylindole-2-carboxamides in [Pd]-catalysed C-H activation and phase transfer catalysis: formation of pyrrolo-diindolones vs. β-carbolinones. Org Biomol Chem. 2016; 14(19):4519-33. DOI: 10.1039/c6ob00583g. View

12.

Duguet N, Slawin A, Smith A . An asymmetric hetero-claisen approach to 3-alkyl-3-aryloxindoles. Org Lett. 2009; 11(17):3858-61. DOI: 10.1021/ol901441t. View

13.

Solorio-Alvarado C, Echavarren A . Gold-catalyzed annulation/fragmentation: formation of free gold carbenes by retro-cyclopropanation. J Am Chem Soc. 2010; 132(34):11881-3. DOI: 10.1021/ja104743k. View

14.

Morris L, Nance K, Gentry P, Days E, Weaver C, Niswender C . Discovery of (S)-2-cyclopentyl-N-((1-isopropylpyrrolidin2-yl)-9-methyl-1-oxo-2,9-dihydro-1H-pyrrido[3,4-b]indole-4-carboxamide (VU0453379): a novel, CNS penetrant glucagon-like peptide 1 receptor (GLP-1R) positive allosteric modulator (PAM). J Med Chem. 2014; 57(23):10192-7. PMC: 4266362. DOI: 10.1021/jm501375c. View

15.

Abbiati G, Beccalli E, Broggini G, Zoni C . Regioselectivity on the palladium-catalyzed intramolecular cyclization of indole derivatives. J Org Chem. 2003; 68(20):7625-8. DOI: 10.1021/jo034636v. View

16.

Harris J, Padwa A . A new beta-carbolinone synthesis using a Rh(II)-promoted [3 + 2]-cycloaddition and Pd(0) cross-coupling/Heck cyclization chemistry. Org Lett. 2003; 5(22):4195-7. DOI: 10.1021/ol0356338. View

17.

Hachiya I, Nakamura K, Hara M, Sato K, Shimizu M . Domino 1,4- and 1,6-Addition Reactions of Ketene Silyl Acetals to Dialkynyl Imines Promoted by Aluminum Chloride: Synthesis of Multifunctionalized β-Lactams. J Org Chem. 2019; 84(22):14770-14794. DOI: 10.1021/acs.joc.9b02364. View

18.

Veale C, Damewood Jr J, Steelman G, Bryant C, Gomes B, Williams J . Non-peptidic inhibitors of human leukocyte elastase. 4. Design, synthesis, and in vitro and in vivo activity of a series of beta-carbolinone-containing trifluoromethyl ketones. J Med Chem. 1995; 38(1):86-97. DOI: 10.1021/jm00001a014. View

19.

Tsvelikhovsky D, Buchwald S . Synthesis of heterocycles via Pd-ligand controlled cyclization of 2-chloro-N-(2-vinyl)aniline: preparation of carbazoles, indoles, dibenzazepines, and acridines. J Am Chem Soc. 2010; 132(40):14048-51. PMC: 2951481. DOI: 10.1021/ja107511g. View

20.

Tian Z, Xu J, Liu B, Tan Q, Xu B . Copper-Catalyzed Synthesis of Polysubstituted Pyrroles through [3+1+1] Cycloaddition Reaction of Nitrones and Isocyanides. Org Lett. 2018; 20(9):2603-2606. DOI: 10.1021/acs.orglett.8b00798. View