An improved process for the N-alkylation of indoles using chiral N-protected 2-methylaziridines

Organic Process Research and Development

Volumn 7, Issue 1, 2003, Pages 22-24

  Giles, Paul R ^a   Rogers Evans, Mark ^b   Soukup, Milan ^b   Knight, John ^a  

^a Vernalis PLC   (United Kingdom)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

AZIRIDINE DERIVATIVE; INDOLE DERIVATIVE;

ALKYLATION; ARTICLE; CHIRALITY; METHODOLOGY; PROCESS DEVELOPMENT;

EID: 0037286391     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op020078v     Document Type: Article

References (10)

1. Boes, M.; Jenck, F.; Martin, J. R.; Moreau, J.-L.; Sleight, A. J.; Wichmann, J.; Widmer, U. J. Med. Chem. 1997, 40, 2762-2769.
2. Rogers-Evans, M.; Soukup, M. PCT Int. Appl., WO 9747598 A1, 1997; Chem. Abstr. 1998, 128, 75296.
3. Adams, D. R.; Bentley, J. M.; Roffey, J. R. A.; Hamlyn, R. J.; Gaur, S.; Duncton, M. A.; Bebbington, D.; Monck, N. J.; Dawson, C. E.; Pratt, R. M.; George, A. R. PCT Int. Appl. WO 0012475, 2000; Chem. Abstr. 2000, 132, 194289.
4. The internal standard was weighed into the reaction vessel prior to addition of the solvent and base. Samples (0.5 mL) of the reaction mixture were taken for analysis and diluted with 10% aqueous acetic acid and methanol prior to injection onto HPLC using the Vernalis conditions as described in the Experimental Section. Typical retention times of the species are indole 1b, 3.76 min; alkylated product 3b, 5.78 min; internal standard 9.8 min; deprotected amine 4b, 2.85 min.
5. Conversion of -BOC-alaninyl mesylate 2 to the corresponding aziridine 5 has been reported using 4 equiv of KOH and 1.2 equiv TsCl in ether; see Wessig, P.; Schwarz, J. Synlett 1997, 893.
6. Onistschenko, A.; Stamm, H. Chem. Ber. 1989, 122, 2397.
7. 2O: Shima, I.; Shimazaki, N.; Imai, K.; Hemmi, K.; Hasimoto, M. Chem. Pharm. Bull. 1990, 38, 564; using scandium triflate: Bennani, Y. L.; Zhu, G.-D.; Freeman, J. C. Synlett 1998, 754.
8. 2O: Shima, I.; Shimazaki, N.; Imai, K.; Hemmi, K.; Hasimoto, M. Chem. Pharm. Bull. 1990, 38, 564; using scandium triflate: Bennani, Y. L.; Zhu, G.-D.; Freeman, J. C. Synlett 1998, 754.
9. Mansell, H. L. Unpublished results.
10. Roffey, J. R. A.; Duncton, M. A.; Dawson, C. E.; Hamlyn, R. J. Unpublished results.