mabuterol

{{Short description|Chemical compound}}

{{Infobox drug

| drug_name = Mabuterol

| image = Mabuterol.svg

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| CAS_number = 56341-08-3

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| PubChem = 3995

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| DrugBank =

| ChemSpiderID = 3857

| UNII = R4K19W6S7Q

| KEGG =

| ChEBI = 135325

| ChEMBL = 86749

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| synonyms = Mabuterolum; PB 868Cl

| IUPAC_name = 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]-2-(tert-butylamino)ethanol

| C=13 | H=18 | Cl=1 | F=3 | N=2 | O=1

| SMILES = Clc1cc(cc(c1N)C(F)(F)F)C(O)CNC(C)(C)C

| StdInChI = 1S/C13H18ClF3N2O/c1-12(2,3)19-6-10(20)7-4-8(13(15,16)17)11(18)9(14)5-7/h4-5,10,19-20H,6,18H2,1-3H3

| StdInChIKey = JSJCTEKTBOKRST-UHFFFAOYSA-N

}}

Mabuterol is a selective β2 adrenoreceptor agonist.{{cite journal | vauthors = Osada E, Murai T, Ishizaka Y, Sanai K | title = Pharmacological studies of mabuterol, a new selective beta 2-stimulant. II: Effects on the cardiovascular system and smooth muscle organs | journal = Arzneimittel-Forschung | volume = 34 | issue = 11A | pages = 1641–1651 | date = 1984 | pmid = 6152157 }}{{cite journal | vauthors = Akahane K, Furukawa Y, Ogiwara Y, Haniuda M, Chiba S | title = Beta-adrenoceptor blocking effects of a selective beta 2-agonist, mabuterol, on the isolated, blood-perfused right atrium of the dog | journal = British Journal of Pharmacology | volume = 97 | issue = 3 | pages = 709–716 | date = July 1989 | pmid = 2474351 | pmc = 1854580 | doi = 10.1111/j.1476-5381.1989.tb12007.x }}

Synthesis

File:Mabuterol synthesis.svg

The halogenation of 2-(Trifluoromethyl)aniline [88-17-5] (1) with iodine and sodium bicarbonate resulted in 2-Amino-5-Iodobenzotrifluoride [97760-97-9] (2). Protection with acetic anhydride followed by nucleophilic aromatic displacement with copper(I)cyanide gave N-[4-cyano-2-(trifluoromethyl)phenyl]acetamide [175277-96-0] (3). Hydrolysis of the nitrile and the protecting group gave 4-amino-3-(trifluoromethyl)benzoic acid [400-76-0] (4). Halogenation with chlorine gave 4-Amino-3-Chloro-5-(Trifluoromethyl)Benzoic Acid [95656-52-3] (5). Halogenation of the acid with thionyl chloride gave 4-Amino-3-chloro-5-(trifluoromethyl)benzoylchloride [63498-15-7] (6). Treatment with diethyl malonate [105-53-3] gave the acetophenone and hence 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]ethanone [97760-76-4] (7). Halogenation with bromine in acetic acid led to 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]-2-bromoethanone [97760-87-7] (8). Treatment with tert-butylamine [75-64-9] yielded 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]-2-(tert-butylamino)ethenone, [https://pubchem.ncbi.nlm.nih.gov/compound/13355601 CID:13355601] (9). Reduction of the ketone with sodium borohydride completed the synthesis of Mabuterol (10).

See also

References