Spirodecanone

Last updated
Spirodecanone
Spirodecanone.svg
Names
Other names
1-Phenyl-1,3,8-triazaspiro[4,5]decan-4-one
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
EC Number
  • 213-819-5
MeSH spirodecanone
PubChem CID
  • InChI=1S/C13H17N3O/c17-12-13(6-8-14-9-7-13)16(10-15-12)11-4-2-1-3-5-11/h1-5,14H,6-10H2,(H,15,17)
    Key: HTQWGIHCFPWKAS-UHFFFAOYSA-N
  • C1CNCCC12C(=O)NCN2C3=CC=CC=C3
Properties
C13H17N3O
Molar mass 231.299 g·mol−1
Density g/cm3 (20 °C)
Hazards
GHS labelling:
GHS-pictogram-exclam.svg
Warning
H315, H319, H335
P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Spirodecanone refers to a class of spirocyclic ketones, often studied for their potential applications in medicinal chemistry. One notable example is 1-Phenyl-1,3,8-triazaspiro[4.5]decan-4-one, which has been investigated as a metabolite of neuroleptic agents like Fluspirilene. It has a molecular formula of C13H17N3O and a melting point of 188-191 °C.

Contents

Synthesis

The original synthesis was first disclosed by Paul Janssen, [1] and was covered by Daniel Lednicer in one of his books. [2]

A recent synthesis of spirodecanone is disclosed: [3] [4]

Spirodecanone synthesis.svg

The Strecker-like condensation between N-benzyl-4-piperidone [3612-20-2] (1), aniline and TMSCN [7677-24-9], gives 4-anilino-1-benzylpiperidine-4-carbonitrile [968-86-5] (2). Acid catalyzed partial hydrolysis of the nitrile to the amide afforded 4-anilino-1-benzylpiperidine-4-carboxamide [1096-03-3] (3). Reaction with DMF-DMA  [ de ] forms the spiroimidazolidone ring giving 8-benzyl-1-phenyl-1,3,8-triazaspiro[4.5]dec-2-en-4-one [974-42-5] (4). The imine bond is reduced with sodium borohydride giving 8-benzyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one [974-41-4] (5). Catalytic hydrogenation then removes the benzyl group (6).

It is noteworthy to mention that intermediate 4 finds dual use in the synthesis of some highly potent fentanyl analogs. [5]

Applications

Listed in alphabetical order:

  1. Fluspiperone is similar but with additional para-fluoro.
  2. Fluspirilene
  3. L008716
  4. Phencyclidine analog [6]
  5. R-5260 [1109-69-9] (normethadone analog)
  6. R 6890 (spirochlorphine)
  7. RP-23618 [207991-30-8]
  8. Spiramide
  9. Spiroxatrine contains a Benzodioxan sidechain.
  10. Spirilene [357-66-4]
  11. Spiperone
  12. Ro64-6198 & Ro65-6570 (NOP receptor agonist).
  13. BRN 4620880 [99756-32-8]
  14. 8-(5,8-Dichloro-1,2,3,4-tetrahydro-2-naphthyl)-1-phenyl-1,3,8-triaza-spiro(4.5)decan-4-one. [7]

References

  1. ↑ Janssen Paul Adriaan Jan, US3155669, US3155670, US3161644 & US3238216 (1964, 1964, 1964 & 1966 all to Research Laboratorium C Janssen NV).
  2. ↑ Strategies for Organic Drug Synthesis and Design, second edition, by Daniel Lednicer (page 335).
  3. ↑ Morciano, G., Preti, D., Pedriali, G., Aquila, G., Missiroli, S., Fantinati, A., Caroccia, N., Pacifico, S., Bonora, M., Talarico, A., Morganti, C., Rizzo, P., Ferrari, R., Wieckowski, M. R., Campo, G., Giorgi, C., Trapella, C., Pinton, P. (23 August 2018). "Discovery of Novel 1,3,8-Triazaspiro[4.5]decane Derivatives That Target the c Subunit of F 1 /F O -Adenosine Triphosphate (ATP) Synthase for the Treatment of Reperfusion Damage in Myocardial Infarction". Journal of Medicinal Chemistry. 61 (16): 7131–7143. doi:10.1021/acs.jmedchem.8b00278. hdl: 11392/2397146 . PMID   30060655.
  4. ↑ 盛春泉, et al. CN113480536 (2021 to Second Military Medical University SMMU).
  5. ↑ Walz, A. J., Hsu, F.-L. (January 2014). "Synthesis of 4-anilinopiperidine methyl esters, intermediates in the production of carfentanil, sufentanil, and remifentanil". Tetrahedron Letters. 55 (2): 501–502. doi:10.1016/j.tetlet.2013.11.058.
  6. ↑ Alberati, D., Hainzl, D., Jolidon, S., Kurt, A., Pinard, E., Thomas, A. W., Zimmerli, D. (August 2006). "4-Substituted-8-(1-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of highly selective GlyT1 inhibitors with superior pharmacological and pharmacokinetic parameters". Bioorganic & Medicinal Chemistry Letters. 16 (16): 4321–4325. doi:10.1016/j.bmcl.2006.05.063. PMID   16762550.
  7. ↑ Röver, S., Adam, G., Cesura, A. M., Galley, G., Jenck, F., Monsma, F. J., Wichmann, J., Dautzenberg, F. M. (6 April 2000). "High-Affinity, Non-Peptide Agonists for the ORL1 (Orphanin FQ/Nociceptin) Receptor". Journal of Medicinal Chemistry. 43 (7): 1329–1338. doi:10.1021/jm991129q. PMID   10753470.
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