Determination of the source of the N-methyl impurity in the synthesis of pemetrexed disodium heptahydrate

Organic Process Research and Development

Volumn 9, Issue 6, 2005, Pages 738-742

  Kjell, Douglas P ^a   Hallberg, Dallas W ^a   Kalbfleisch, J Michael ^a   McCurry, Cynthia K ^a   Semo, Michael J ^a   Sheldon, Edward M ^a   Spitler, Jeremy T ^a   Wang, Ming ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 28944434992     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op0498013     Document Type: Article

References (11)

1. International Conference on Harmonisation (ICH) Guidelines, Q3A(R), Impurities in New Drug Substances (Revised Guideline), 2002.
2. Kjell, D. P.; Slattery, B. J.; Semo, M. J. J. Org. Chem. 1999, 64, 5722-5724.
3. Barnett, C. J.; Wilson, T. M.; Kobierski, M. E. Org. Proc. Res. Dev. 1999, 3, 184-188.
4. Based on an informal survey, and personal experience, <2-3% total related substances would be a more typical specification for an early intermediate.
5. Kaminski, Z. J. Tetrahedron Lett. 1985, 26, 2901-2904.
6. Munesada, K.; Suga, T. J. Org. Chem. 1987, 52, 5655-5662.
7. Kunishima, M.; Kawachi, C; Morita, J.; Terao, K.; Iwasaki, F.; Tani, S Tetrahedron 1999, 55, 13159-13170.
8. Upon review, use of N-ethylmorpholine instead of DBU was suggested.
9. Prepared by use of appropriately labeled methanol in the procedure described in: Cronin, J. S.; Ginah, F. O.; Murray, A. R.; Copp, J. D. Synth. Commun. 1996, 26, 3491-3494.
10. Obtained from Aldrich.
11. Willker, W.; Leibfritz, D.; Kerssebaum, R.; Bermel, W. Magn. Reson. Chem. 1993, 31, 287-292.