Chlorproethazine

Chlorproethazine

Names
Preferred IUPAC name 3-(2-Chlorophenothiazin-10-yl)-N,N-diethylpropan-1-amine
Other names RP-4909
Identifiers
CAS Number	84-01-5^Y 4611-02-3 (HCl)^Y
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL2105938^N
ChemSpider	59173^N
ECHA InfoCard	100.001.373
KEGG	D07308^Y
PubChemCID	65750
UNII	960NX27Z07^Y 520P4U8V2Z (HCl)^Y
CompTox Dashboard(EPA)	DTXSID80232882
InChI InChI=1S/C19H23ClN2S/c1-3-21(4-2)12-7-13-22-16-8-5-6-9-18(16)23-19-11-10-15(20)14-17(19)22/h5-6,8-11,14H,3-4,7,12-13H2,1-2H3^N Key: DBOUGBAQLIXZLV-UHFFFAOYSA-N^N InChI=1/C19H23ClN2S/c1-3-21(4-2)12-7-13-22-16-8-5-6-9-18(16)23-19-11-10-15(20)14-17(19)22/h5-6,8-11,14H,3-4,7,12-13H2,1-2H3 Key: DBOUGBAQLIXZLV-UHFFFAOYAP
SMILES Clc2cc1N(c3c(Sc1cc2)cccc3)CCCN(CC)CC
Properties
Chemical formula	C19H23ClN2S
Molar mass	346.91732 g/mol
Pharmacology
ATC code	N05AA07 (WHO)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is ^YN ?) Infobox references

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 topicalcream for the treatment of muscle pain.^{[1][2][3][4][5]} It has been associated with photoallergiccontact dermatitis.^[6][7]

Synthesis

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

Patent:^[8]

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).

References

1. Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 264–. ISBN 978-1-4757-2085-3.
2. Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 222–. ISBN 978-3-88763-075-1.
3. Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 74–. ISBN 978-94-011-4439-1.
4. William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia. Elsevier. pp. 989–. ISBN 978-0-8155-1856-3.
5. "Chlorproethazine". Drugs.com. Archived from the original on 27 September 2017.
6. Rietschel RL, Fowler JF, Fisher AA (2008). Fisher's Contact Dermatitis. PMPH-USA. pp. 249–. ISBN 978-1-55009-378-0.
7. Johansen JD, Frosch PJ, Lepoittevin JP (29 September 2010). Contact Dermatitis. Springer Science & Business Media. pp. 373–. ISBN 978-3-642-03827-3.
8. US 2769002, Buisson P, Gailliot P, "Preparation of Phenothiazine Compounds", issued 30 October 1956, assigned to Rhône-Poulenc