Chlorproethazine Explained

Chlorproethazine, sold under the brand name Neuriplege, is a drug of the phenothiazine group described as a muscle relaxant or tranquilizer which is or has been marketed in Europe as a topical cream for the treatment of muscle pain.^{[1] [2] [3] [4] [5]} It has been associated with photoallergic contact dermatitis.^{[6] [7]}

Synthesis

Chlorproethazine can be synthesized from a diphenylsulfide derivative. The general scheme is sufficiently flexible to permit the interchange of the order of some of the steps.

Thus alkylation of 2-(2-bromo-phenylsulfanyl)-5-chloro-aniline [105790-02-1] (1) with 3-chloro-1-diethylaminopropane [104-77-8] (2) leads to the intermediate (3). Ring closure as above by nucleophilic aromatic displacement leads to the antipsychotic drug chlorproethazine (4).

The last step uses copper powder and is a form of the Ullmann condensation (i.e. the Goldberg reaction).

Notes and References

1. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 264–.
2. Book: Index Nominum 2000: International Drug Directory. 2000. Taylor & Francis. 978-3-88763-075-1. 222–.
3. Book: Morton IK, Hall JM . Concise Dictionary of Pharmacological Agents: Properties and Synonyms. 6 December 2012. Springer Science & Business Media. 978-94-011-4439-1. 74–.
4. Book: William Andrew Publishing. Pharmaceutical Manufacturing Encyclopedia. 22 October 2013. Elsevier. 978-0-8155-1856-3. 989–.
5. Web site: Chlorproethazine . Drugs.com . https://web.archive.org/web/20170927160117/https://www.drugs.com/international/chlorproethazine.html . 27 September 2017 . dead .
6. Book: Rietschel RL, Fowler JF, Fisher AA . Fisher's Contact Dermatitis. 2008. PMPH-USA. 978-1-55009-378-0. 249–.
7. Book: Johansen JD, Frosch PJ, Lepoittevin JP . Contact Dermatitis. 29 September 2010. Springer Science & Business Media. 978-3-642-03827-3. 373–.