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 and a melting point of 188-191 °C.
Synthesis The original synthesis was first disclosed by Paul Janssen,Janssen Paul Adriaan Jan, US3155669, US3155670, US3161644 & US3238216 (1964, 1964, 1964 & 1966 all to Research Laboratorium C Janssen NV). and was covered by Daniel Lednicer in one of his books.Strategies for Organic Drug Synthesis and Design, second edition, by Daniel Lednicer (page 335).
A recent synthesis of spirodecanone is disclosed:盛春泉, et al. CN113480536 (2021 to Second Military Medical University SMMU).
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 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.
Applications Listed in alphabetical order: DiPOA Fluspiperone is similar but with additional para-fluoro. Fluspirilene L008716 Phencyclidine analog R-5260 [1109-69-9] (normethadone analog) R 6890 (spirochlorphine) RP-23618 [207991-30-8] Spiramide Spiroxatrine contains a Benzodioxan sidechain. Spirilene [357-66-4] Spiperone Ro64-6198 & Ro65-6570 (NOP receptor agonist). BRN 4620880 [99756-32-8] 8-(5,8-Dichloro-1,2,3,4-tetrahydro-2-naphthyl)-1-phenyl-1,3,8-triaza-spiro(4.5)decan-4-one.
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