One-pot Synthesis of 2-amino-indole-3-carboxamide and Analogous

Overview

Journal ACS Comb Sci

Publisher American Chemical Society

Specialty Chemistry

Date 2011 Mar 15

PMID 21395342

Citations 3

Authors

Kan Wang

Eberhardt Herdtweck

Alexander Domling

Affiliations

Soon will be listed here.

Abstract

An efficient one-pot, two-step solution-phase synthetic method was developed to synthesize twenty-three 2-amino-indole-3-carboxamides (3) from 2-halonitrobenzene (1) or heterocyclic analogous and cyanoacetamides (2). In this sequence, first, intermediate 2-cyano-2-(2-nitrophenyl)acetamide (4) was generated under basic condition via S(NAr) reaction; after direct addition of hydrochloric acid solution, FeCl(3), and Zn powder, indole 3 was generated via reduction/cyclization process.

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References

Willemann C, Grunert R, Bednarski P, Troschutz R . Synthesis and cytotoxic activity of 5,6-heteroaromatically annulated pyridine-2,4-diamines. Bioorg Med Chem. 2009; 17(13):4406-19. DOI: 10.1016/j.bmc.2009.05.016. View

Zhu Z, Sun Z, Ye Y, Voigt J, Strickland C, Smith E . Discovery of cyclic acylguanidines as highly potent and selective beta-site amyloid cleaving enzyme (BACE) inhibitors: Part I--inhibitor design and validation. J Med Chem. 2010; 53(3):951-65. DOI: 10.1021/jm901408p. View

Hauel N, Nar H, Priepke H, Ries U, Stassen J, Wienen W . Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem. 2002; 45(9):1757-66. DOI: 10.1021/jm0109513. View

Czarna A, Beck B, Srivastava S, Popowicz G, Wolf S, Huang Y . Robust generation of lead compounds for protein-protein interactions by computational and MCR chemistry: p53/Hdm2 antagonists. Angew Chem Int Ed Engl. 2010; 49(31):5352-6. PMC: 3772515. DOI: 10.1002/anie.201001343. View

Siddiqui F, Qureshi A . Dabigatran etexilate, a new oral direct thrombin inhibitor, for stroke prevention in patients with atrial fibrillation. Expert Opin Pharmacother. 2010; 11(8):1403-11. DOI: 10.1517/14656566.2010.482931. View

Kuhn B, Mohr P, Stahl M . Intramolecular hydrogen bonding in medicinal chemistry. J Med Chem. 2010; 53(6):2601-11. DOI: 10.1021/jm100087s. View

Wang K, Kim D, Domling A . Cyanoacetamide MCR (III): three-component Gewald reactions revisited. J Comb Chem. 2009; 12(1):111-8. PMC: 3721980. DOI: 10.1021/cc9001586. View

Wang K, Domling A . Design of a versatile multicomponent reaction leading to 2-amino-5-ketoaryl pyrroles. Chem Biol Drug Des. 2010; 75(3):277-83. DOI: 10.1111/j.1747-0285.2009.00942.x. View

Wang D, Sun M, Liu G . Substituent diversity-directed synthesis of indole derivatives. J Comb Chem. 2009; 11(4):556-75. DOI: 10.1021/cc800198p. View

10.

Wang K, Nguyen K, Huang Y, Domling A . Cyanoacetamide multicomponent reaction (I): Parallel synthesis of cyanoacetamides. J Comb Chem. 2009; 11(5):920-7. DOI: 10.1021/cc9000778. View

11.

Eriksson B, Smith H, Yasothan U, Kirkpatrick P . Dabigatran etexilate. Nat Rev Drug Discov. 2008; 7(7):557-8. DOI: 10.1038/nrd2622. View

12.

Deutsch H, Shi Q, Gruszecka-Kowalik E, Schweri M . Synthesis and pharmacology of potential cocaine antagonists. 2. Structure-activity relationship studies of aromatic ring-substituted methylphenidate analogs. J Med Chem. 1996; 39(6):1201-9. DOI: 10.1021/jm950697c. View

13.

Hajduk P, Boyd S, Nettesheim D, Nienaber V, Severin J, Smith R . Identification of novel inhibitors of urokinase via NMR-based screening. J Med Chem. 2000; 43(21):3862-6. DOI: 10.1021/jm0002228. View

14.

Putnam C, Arvai A, Bourne Y, Tainer J . Active and inhibited human catalase structures: ligand and NADPH binding and catalytic mechanism. J Mol Biol. 2000; 296(1):295-309. DOI: 10.1006/jmbi.1999.3458. View

15.

Yan C, Wang Q, Song X, Sun J . One-step synthesis of pyrido[1,2-a]benzimidazole derivatives by a novel multicomponent reaction of chloroacetonitrile, malononitrile, aromatic aldehyde, and pyridine. J Org Chem. 2008; 74(2):710-8. DOI: 10.1021/jo802166t. View

16.

Yu S, Qin D, Shangary S, Chen J, Wang G, Ding K . Potent and orally active small-molecule inhibitors of the MDM2-p53 interaction. J Med Chem. 2009; 52(24):7970-3. PMC: 2795799. DOI: 10.1021/jm901400z. View

17.

Popowicz G, Czarna A, Wolf S, Wang K, Wang W, Domling A . Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery. Cell Cycle. 2010; 9(6):1104-11. DOI: 10.4161/cc.9.6.10956. View

18.

Kertesz D, Brotherton-Pleiss C, Yang M, Wang Z, Lin X, Qiu Z . Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-benzyl derivatives with broad potency against resistant mutant viruses. Bioorg Med Chem Lett. 2010; 20(14):4215-8. DOI: 10.1016/j.bmcl.2010.05.040. View