A Novel Strategy for the Synthesis of N-Alkylated Oxindoles

Nguyen Duc Thien; Hoang Kim Ngoc; Nguyen-Hai Nam; Duong Tien Anh; Daniel Baecker

doi:10.1055/s-0043-1775460

Synlett, Table of Contents

Synlett 2025; 36(17): 2925-2929
DOI: 10.1055/s-0043-1775460

letter

Small Molecules in Medicinal Chemistry

A Novel Strategy for the Synthesis of N-Alkylated Oxindoles

Authors

Nguyen Duc Thien

^aHanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, 100000, Vietnam
Hoang Kim Ngoc

^aHanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, 100000, Vietnam
Nguyen-Hai Nam

^aHanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, 100000, Vietnam
Duong Tien Anh∗

^aHanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, 100000, Vietnam
Daniel Baecker ∗

^bDepartment of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Straße 2+4, 14195 Berlin, Germany

Abstract

All articles of this category

Abstract

The synthesis of N-alkylated oxindoles remains an important focus in organic chemistry, due to their common occurrence in bioactive compounds and pharmaceutical agents. An efficient novel strategy for alkylating the oxindole scaffold at the N-1 position is described. By using (N-methylpyrrol-2-yl)methylidene as a protecting group for the competing C-3 position, this methodology provides a simple and mild procedure to convert various oxindoles into their corresponding N-alkylated and N-benzylated derivatives in moderate to good overall yields (up to 67%).

Key words

oxindoles - alkylation - regiochemistry - protecting group

Full Text

References

References and Notes
1 Denoyelle S, Chen T, Yang H, Chen L, Zhang Y, Halperin JA, Aktas BH, Chorev M. Eur. J. Med. Chem. 2013; 69: 537
2 Hewawasam P, Erway M, Moon SL, Knipe J, Weiner H, Boissard CG, Post-Munson DJ, Gao Q, Huang S, Gribkoff VK, Meanwell NA. J. Med. Chem. 2002; 45: 1487
3 Natarajan A, Guo Y, Harbinski F, Fan YH, Chen H, Luus L, Diercks J, Aktas H, Chorev M, Halperin JA. J. Med. Chem. 2004; 47: 4979
4 Steven A, Overman LE. Angew. Chem. Int. Ed. 2007; 46: 5488
5 Millemaggi A, Taylor RJ. Eur. J. Org. Chem. 2010; 2010: 4527
6 Khetmalis YM, Shivani M, Murugesan S, Sekhar KV. G. C. Biomed. Pharmacother. 2021; 141: 111842
7 Uddin MK, Reignier SG, Coulter T, Montalbetti C, Grånäs C, Butcher S, Krog-Jensen C, Felding J. Bioorg. Med. Chem. Lett. 2007; 17: 2854
8 Sharma S, Monga Y, Gupta A, Singh S. RSC Adv. 2023; 13: 14249
9 Al-Warhi T, El Kerdawy AM, Aljaeed N, Ismael OE, Ayyad RR, Eldehna WM, Abdel-Aziz HA, Al-Ansary GH. Molecules 2020; 25: 2031
10 Lobe MM. M, Efange SM. N. R. Soc. Open Sci. 2020; 7: 191316
11 Thakur RK, Joshi P, Upadhyaya K, Singh K, Sharma G, Shukla SK, Tripathi R, Tripathi RP. Eur. J. Med. Chem. 2019; 162: 448
12 Sharma B, Legac J, Cele N, Awolade P, Rosenthal PJ, Singh P, Kumar V. Eur. J. Med. Chem. Rep. 2022; 5: 100052
13 Rouatbi F, Askri M, Nana F, Kirsch G, Sriram D, Yogeeswari P. Tetrahedron Lett. 2016; 57: 163
14 Karki SS, Hazare R, Kumar S, Saxena A, Katiyar A. Turk. J. Pharm. Sci. 2011; 8: 169
15 Singh H, Sindhu J, Khurana JM, Sharma C, Aneja KR. Eur. J. Med. Chem. 2014; 77: 145
16 Romo PE, Insuasty B, Abonia R, del Pilar Crespo M, Quiroga J. Heteroat. Chem. 2020; 8021920
17 Yagnam S, Reddy ER, Trivedi R, Krishna NV, Giribabu L, Rathod B, Prakasham RS, Sridhar B. Appl. Organomet. Chem. 2019; 33: e4817
18 Sampath S, Vadivelu M, Ravindran R, Perumal PT, Velkannan V, Karthikeyan K. ChemistrySelect 2020; 5: 2130
19 Griebel G, Simiand J, Serradeil-Le Gal C, Wagnon J, Pascal M, Scatton B, Maffrand J.-P, Soubrie P. Proc. Natl. Acad. Sci. U.S.A. 2002; 99: 6370
20 Wylie G, Appelboom T, Bolten W, Breedveld FC, Feely J, Leeming MR, Le Loët X, Manthorpe R, Marcolongo R, Smolen J. Br. J. Rheumatol. 1995; 34: 554
21 Sundberg RJ. Indoles . Academic Press; London: 1996
22 Cabri W, Candiani I, Colombo M, Franzoi L, Bedeschi A. Tetrahedron Lett. 1995; 36: 949
23 Jones K, Wilkinson J, Ewin R. Tetrahedron Lett. 1994; 35: 7673
24 Jones KC, McCarthy C. Tetrahedron Lett. 1989; 30: 2657
25 Bowman WR, Heaney H, Jordan BM. Tetrahedron Lett. 1988; 29: 6657
26 Marchese AD, Larin EM, Mirabi B, Lautens M. Acc. Chem. Res. 2020; 53: 1605
27 Poondra RR, Turner NJ. Org. Lett. 2005; 7: 863
28 Lamba M, Singh PR, Tanmay, Goswami A. J. Org. Chem. 2024; 89: 11244
29 Mándoki A, Orsy G, Pászti Z, Porcs-Makkay M, Bogdán D, Simig G, Mándity I, Volk B. Synthesis 2023; 55: 4025
30 Pal S, Guin AK, Chakraborty S, Paul ND. ChemCatChem 2024; 16: e202400026
31 Jensen T, Madsen R. J. Org. Chem. 2009; 74: 3990
32 Kókai E, Simig G, Volk B. Molecules 2016; 22: 24
33 Stillson P, Kahn M. J. Am. Chem. Soc. 1953; 75: 3579
34 Soriano DS. J. Chem. Educ. 1993; 70: 332
35 Crestini C, Saladino R. Synth. Commun. 1994; 24: 2835
36 Jha M, Shelke GM, Kumar A. Eur. J. Org. Chem. 2014; 3334

Supplementary Material

Supporting Information (PDF)