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药物详细合成路线

Name Azosemide;SK 110;PLE 1053;Diart;Luret
Chemical Name 2-Chloro-5-(1H-tetrazol-5-yl)-4-(2-thienylmethylamino)benzenesulfonamide
CAS 27589-33-9
Related CAS
Formula C12H11ClN6O2S2
Structure
Formula Weight 370.84147
Stage 上市
Company Roche (Originator), Sanofi-synthélabo (Licensee)
Activity/Mechanism Diuretics, RENAL-UROLOGIC DRUGS
Syn. Route 2
Route 1
a new synthetic procedure for azosemide has been reported:the condensation of 2-formylthiophene (i) with 2-chloro-4-amino-5-(5-tetrazolyl)benzenesulfonamide (ii) by means of polyphosphoric acid (ppa) in dmso gives the corresponding schiff base (iii), which is reduced with kbh4 in the same solvent.
List of intermediates No.
3-nitrophenyl 2-quinolinylmethyl ether; 2-[(3-nitrophenoxy)methyl]quinoline (i)
ethyl 3-(2,4-dichloro-3,5-difluorophenyl)-3-oxopropanoate (ii)
1-[[chloro(cyclopropylimino)methyl]sulfanyl]benzene (iii)
Reference 1:
    baetz, f.; lauer, k. (boehringer ingelheim gmbh); process for the production of 5-(4-chloro-5-sulfamoyl-2-thenylamino)phenyltetrazole. de 3034664; jp 57081485 .

Route 2
the reaction of 2-fluoro-4-chloro-5-sulfamoylbenzoic acid (i) with refluxing socl2 gives the corresponding acyl chloride (ii), which by reaction with aqueous nh3 is transformed into the amide (iii). the dehydration of (iii) with refluxing pocl3 affords the nitrile (iv), which is then condensed with thenylamine (v) to yield 4-chloro-2-thenylamino-5-sulfamoylbenzonitrile (vi). finally, this compound is cyclized with sodium azide in dmf at 100 c.
List of intermediates No.
(e)-3-amino-2-chloro-2-propenal (i)
(ii)
n-[(e)-2-chloro-3-(dimethylamino)-2-propenylidene]-n-methylmethanaminium chloride (iii)
6-ethyl-5-fluoro-4-pyrimidinol (iv)
4-(1-bromoethyl)-6-chloro-5-fluoropyrimidine (v)
2,4-dichloro-5-fluoropyrimidine (vi)
Reference 1:
    popelak, a.; et al. (boehringer ingelheim gmbh); 5-phenyltetrazole derivatives. de 1815922; fr 2026688; gb 1237790; us 3665002 .
Reference 2:
    serradell, m.n.; castaner, j.; blancafort, p.; hillier, k.; azosemide. drugs fut 1979, 4, 6, 393.