Cilobamine Explained

Iupac Name:	(2R,3R)-2-(3,4-Dichlorophenyl)-3-[(1-methylethyl)amino]bicyclo[2.2.2]octan-2-ol
Width:	200
Cas Number:	69429-84-1
Atc Prefix:	none
Pubchem:	299379
Chemspiderid:	8557262
Chembl:	2106470
Unii:	067U1T4S30
C:	17
H:	23
Cl:	2
N:	1
O:	1
Smiles:	Clc1ccc(cc1Cl)[C@@]3(O)[C@H](NC(C)C)C2CCC3CC2

Cilobamine is a drug which acts as a norepinephrine-dopamine reuptake inhibitor (NDRI) and has stimulant and antidepressant effects.^{[1] [2]}

It can clearly be seen that the structure is based on dichloroisoprenaline that has been fused onto the bicycloalkane scaffold.

Synthesis

An intramolecular Dieckmann cyclization on methyl 4-(2-methoxy-2-oxoethyl)cyclohexanecarboxylate [1401222-79-4] (3) with sodium hydride base gives reaction Methyl 3-oxobicyclo[2.2.2]octane-2-carboxylate [30144-30-0] (4). Treatment with sodium nitrite introduces an isonitroso group adjacent to the ketone, giving 3-Hydroxyiminobicyclo[2.2.2]octan-2-one, CID:131066320 (5). Addition of the aryl Grignard reagent, and reduction of the oxime gives CID:154108204 (6). A reductive amination of the primary amino group with acetone then completed the synthesis of cilobamine (7).

See also

• Fencamfamine
• Manifaxine

Notes and References

1. Leeson GA, Shaath ZA, Biedenbach SA, Yarrington JT, Okerholm RA . Dose related induction of the drug metabolizing enzymes of rat liver by cilobamine . Fundamental and Applied Toxicology . 4 . 2 Pt 1 . 261–9 . April 1984 . 6724198 . 10.1016/0272-0590(84)90127-1 .
2. Wager S, Quitkin F, Stewart J, McGrath P, Harrison W, Markowitz J, Tricamo E . Cilobamine in the treatment of atypical depression . Human Psychopharmacology: Clinical and Experimental . 1988 . 201–205. 3 . 3 . 10.1002/hup.470030308 . 145253439 .