1-Methyl-4-piperidone

1-Methyl-4-piperidone
Names
Preferred IUPAC name
1-Methylpiperidin-4-one
Other names
N-Methyl-4-piperidone
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.014.450
EC Number
  • 215-895-5
UNII
  • InChI=1S/C6H11NO/c1-7-4-2-6(8)3-5-7/h2-5H2,1H3
    Key: HUUPVABNAQUEJW-UHFFFAOYSA-N
  • CN1CCC(=O)CC1
Properties
C6H11NO
Molar mass 113.160 g·mol−1
Density 0.92–0.98 g/cm3 (20°C)
Boiling point 55–60 °C (131–140 °F; 328–333 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

1-Methyl-4-piperidone (also known as N-methyl-4-piperidone) is a clear dark yellow liquid organic compound with molecular formula C6H11NO. It is the N-methyl substituted variant of 4-piperidone.[1]

Applications

1-Methyl-4-piperidone is used as a building block for a variety of pharmaceuticals, including:

Synthesis

The first synthesis of 1-methyl-4-piperidone was reported by Samuel M. McElvain in 1948.[33] The method involves double Michael reaction between methylamine and two equivalents of ethyl acrylate, a Dieckmann cyclization (i.e. intramolecular Claisen condensation), saponification and decarboxylation.

Another synthesis uses methylamine, formaldehyde and the ethyl ester of acetonedicarboxylic acid.[34]

A third synthesis consists of the ring closing of 1,5-dichloro-3-pentanone with methylamine.[35]

See also

References

  1. ↑ "SAFETY DATA SHEET". Retrieved 2025-06-11.
  2. ↑ "Azacyclic compounds for use in the treatment of serotonin related diseases". Google Patents. March 6, 2001. Retrieved June 27, 2025.
  3. ↑ Villani, F. J., Mann, T. A., Wefer, E. A., Hannon, J., Larca, L. L., Landon, M. J., Spivak, W., Vashi, D., Tozzi, S. (January 1975). "Benzopyranopyridine derivatives. 1. Aminoalkyl derivatives of the azaxanthenes as bronchodilating agents". Journal of Medicinal Chemistry. 18 (1): 1–8. doi:10.1021/jm00235a001.
  4. ↑ Eistetter K, Kley HP, Menge HG, Schaefer H (1983). "B-777-81". Drugs of the Future. 8 (5): 387. doi:10.1358/dof.1983.008.05.65796.
  5. ↑ "Anti-depressant and analgesic 4-phenoxypiperidines". Google Patents. July 11, 1980. Retrieved June 11, 2025.
  6. ↑ "4-Aryl-4-aryloxypiperidines". Google Patents. September 3, 1980. Retrieved June 11, 2025.
  7. ↑ "X-tertiary amino-i-alkyl-piperidines". Google Patents. July 13, 1954. Retrieved June 11, 2025.
  8. ↑ Bandyopadhyaya, Achintya; Rajagopalan, Desikan R.; Rath, Nigam P.; Herrold, Amy; Rajagopalan, Raghavan; Napier, T. Celesete; Tedford, Clark E.; Rajagopalan, Parthasarathi (2012). "The synthesis and receptor binding affinities of DDD-016, a novel, potential, atypical antipsychotic". MedChemComm. 3 (5): 580. doi:10.1039/c2md00311b. ISSN 2040-2503. Retrieved 2025-06-11.
  9. ↑ van Der Stelt, C.; Harms, A. F.; Nauta, W. Th. (1961). "The Effect of Alkyl-Substitution in Drugs--V. Synthesis and Chemical Properties of Some Dibenzo [a,d]1,4-cycloheptadienyl Ethers". Journal of Medicinal and Pharmaceutical Chemistry. 4 (2): 335–349. doi:10.1021/jm50018a008. ISSN 0095-9065. PMID 14039500. Retrieved 2025-06-26.
  10. ↑ CID 11594705 from PubChem
  11. ↑ Van Dijk, J., Hartog, J., Hillen, F. C. (1978). "Progress in Medicinal Chemistry". 6 Non-Tricyclic Antidepressants. Vol. 15. Elsevier. pp. 261–320. doi:10.1016/S0079-6468(08)70258-3. ISBN 9780720406559.
  12. ↑ Jens K. Perregaard, USRE34299 (1993 to H Lundbeck AS).
  13. ↑ Filla, Sandra A.; Mathes, Brian M.; Johnson, Kirk W.; Phebus, Lee A.; Cohen, Marlene L.; Nelson, David L.; Zgombick, John M.; Erickson, Jon A.; Schenck, Kathryn W.; Wainscott, David B.; Branchek, Theresa A.; Schaus, John M. (2003-07-01). "Novel Potent 5-HT 1F Receptor Agonists: Structure−Activity Studies of a Series of Substituted N -[3-(1-Methyl-4-piperidinyl)-1 H -pyrrolo[3,2- b ]pyridin-5-yl]amides". Journal of Medicinal Chemistry. 46 (14): 3060–3071. doi:10.1021/jm030020m. ISSN 0022-2623. PMID 12825944. Retrieved 2025-06-11.
  14. ↑ Hörlein, Ulrich (1954). "Zur Kenntnis der Tetrahydrocarbolin-Verbindungen (I. Mitteil.)". Chemische Berichte. 87 (4): 463–472. doi:10.1002/cber.19540870404. ISSN 0009-2940. Retrieved 2025-06-11.
  15. ↑ "Preparation method of mebhydrolin napadisylate". Google Patents. 2013-01-31. Retrieved 2025-06-11.
  16. ↑ Ennis, E. A., Wright, J., Retzlaff, C. L., McManus, O. B., Lin, Z., Huang, X., Wu, M., Li, M., Daniels, J. S., Lindsley, C. W., Hopkins, C. R., Blakely, R. D. (18 March 2015). "Identification and Characterization of ML352: A Novel, Noncompetitive Inhibitor of the Presynaptic Choline Transporter". ACS Chemical Neuroscience. 6 (3): 417–427. doi:10.1021/cn5001809. PMC 4367188.
  17. ↑ "Molecule of the Month August 2023". School of Chemistry. 2016-08-18. Retrieved 2025-06-11.
  18. ↑ "Process for preparation of naratriptan hydrochloride". Google Patents. 2009-03-09. Retrieved 2025-06-11.
  19. ↑ "A process for the synthesis of naratriptan". Google Patents. 2010-08-18. Retrieved 2025-06-11.
  20. ↑ "Process for preparation of substituted formamidine and substituted N-iminomethyl piperidine". Google Patents. 1983-03-17. Retrieved 2025-06-11.
  21. ↑ "Deuterated pimavanserin 1- (4-flu0r0benzyl) -3- (4-isobutoxybenzyl) -1- ( l-methyl-piperidin-4-yl) -urea". Google Patents. May 8, 2008. Retrieved June 27, 2025.
  22. ↑ "Insecticidal tricyclic derivatives". Google Patents. 2003-09-12. Retrieved 2025-06-11.
  23. ↑ US patent 2903460, Jucker E, Ebnother A, Lindenmann AJ, "Pyrazolone derivatives", issued 1959-09-08, assigned to Sandoz AG
  24. ↑ Ebnöther A, Jucker E, Lindenmann A (1959). "Über neuartige, basisch substituierte Pyrazolon-Derivate. Untersuchungen über synthetische Arzneimittel. 3. Mitteilung". Helvetica Chimica Acta. 42 (4): 1201–1214. doi:10.1002/hlca.19590420415.
  25. ↑ "Piperylone". Pharmaceutical Substances. Thieme. Archived from the original on 2024-07-15. Retrieved 2024-07-17.
  26. ↑ Cole, Derek C.; Ellingboe, John W.; Lennox, William J.; Mazandarani, Hossein; Smith, Deborah L.; Stock, Joseph R.; Zhang, Guoming; Zhou, Ping; Schechter, Lee E. (2005). "N1-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 15 (2). Elsevier BV: 379–383. doi:10.1016/j.bmcl.2004.10.064. ISSN 0960-894X. PMID 15603958.
  27. ↑ Castañer, J., Koch, H. (1983). "Tienocarbine lactate". Drugs of the Future. 8 (6): 516. doi:10.1358/dof.1983.008.06.1003921. ISSN 0377-8282.
  28. ↑ Butler, K. V., Kalin, J., Brochier, C., Vistoli, G., Langley, B., Kozikowski, A. P. (11 August 2010). "Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin A". Journal of the American Chemical Society. 132 (31): 10842–10846. doi:10.1021/ja102758v.
  29. ↑ Ghose, K. (1986). "RS-86". Drugs of the Future. 11 (4): 276. doi:10.1358/dof.1986.011.04.65133. ISSN 0377-8282.
  30. ↑ Cignarella, G., Villa, S., Cattabeni, F., Renò, F., Cimino, M., De Benedetti, P., Barlocco, D. (January 1994). "Synthesis of a new series of 2,8-disubstituted-2,8-diazaspiro[4,5]decan-1-ones as potential muscarinic agonists". European Journal of Medicinal Chemistry. 29 (12): 955–961. doi:10.1016/0223-5234(94)90195-3.
  31. ↑ Palacios JM, Bolliger G, Closse A, Enz A, Gmelin G, Malanowski J. The pharmacological assessment of RS 86 (2-ethyl-8-methyl-2,8-diazaspiro-[4,5]-decan-1,3-dion hydrobromide). A potent, specific muscarinic acetylcholine receptor agonist. Eur J Pharmacol. 1986 Jun 5;125(1):45-62. doi: 10.1016/0014-2999(86)90082-8. PMID: 3732391.
  32. ↑ Bertron, J. L., Ennis, E. A., Tarr, C. J., Wright, J., Dickerson, J. W., Locuson, C. W., Blobaum, A. L., Rook, J. M., Blakely, R. D., Lindsley, C. W. (October 2016). "Optimization of the choline transporter (CHT) inhibitor ML352: Development of VU6001221, an improved in vivo tool compound". Bioorganic & Medicinal Chemistry Letters. 26 (19): 4637–4640. doi:10.1016/j.bmcl.2016.08.062.
  33. ↑ McElvain, S. M., Rorig, K. (May 1948). "Piperidine Derivatives. XVIII. The Condensation of Aromatic Aldehydes with 1-Methyl-4-piperidone". Journal of the American Chemical Society. 70 (5): 1820–1825. Bibcode:1948JAChS..70.1820M. doi:10.1021/ja01185a051. PMID 18861789.
  34. ↑ "A kind of synthetic method of N- methyl -4- piperidones". Google Patents. September 3, 2019. Retrieved June 11, 2025.
  35. ↑ "Synthesis method for N-substituted-4-piperidone". Google Patents. May 24, 2012. Retrieved June 11, 2025.
This page is issued from Wikipedia. The text is available under Creative Commons Attribution-Share Alike 4.0 unless otherwise noted. Additional terms may apply for the media files.