Chemistry:Mabuterol

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Short description: Chemical compound
Mabuterol
Mabuterol.svg
Clinical data
Other namesMabuterolum; PB 868Cl
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
Chemical and physical data
FormulaC13H18ClF3N2O
Molar mass310.75 g·mol−1
3D model (JSmol)

Mabuterol is a selective β2 adrenoreceptor agonist.[1][2]

Synthesis

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Mabuterol synthesis[3][4][5][6][7]

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, CID:13355601 (9). Reduction of the ketone with sodium borohydride completed the synthesis of Mabuterol (10).

See also

References

  1. "Pharmacological studies of mabuterol, a new selective beta 2-stimulant. II: Effects on the cardiovascular system and smooth muscle organs". Arzneimittel-Forschung 34 (11A): 1641–1651. 1984. PMID 6152157. 
  2. "Beta-adrenoceptor blocking effects of a selective beta 2-agonist, mabuterol, on the isolated, blood-perfused right atrium of the dog". British Journal of Pharmacology 97 (3): 709–716. July 1989. doi:10.1111/j.1476-5381.1989.tb12007.x. PMID 2474351. 
  3. "Synthesis of further amino-halogen-substituted phenyl-aminoethanols". Arzneimittel-Forschung 34 (11A): 1612–24. 1984. PMID 6152154. 
  4. Engelhardt G, Keck J, "Aminophenyl ethanolamines and oxazolidines - having analgesic, uterus spasmolytic and anti-spasmodic activity on cross-striped muscle structure", BE patent 808743, issued 1974, assigned to Thomae GmbH.
  5. US patent 4119710, issued 1978, assigned to Boehringer Ing.
  6. DE patent 2351281, assigned to Thomae GmbH.
  7. "Synthesis of stable isotope labeled D9 -Mabuterol, D9 -Bambuterol, and D9 -Cimbuterol". Journal of Labelled Compounds & Radiopharmaceuticals 59 (13): 546–551. November 2016. doi:10.1002/jlcr.3446. PMID 27739098.