超大眼镜蛇什么电影:阿佐酰胺 [CAS:27589-33-9]合成路线图解??有机化学网

药物详细合成路线

Chemical Name： 2-Chloro-5-(1H-tetrazol-5-yl)-4-(2-thienylmethylamino)benzenesulfonamide Generic Name： 阿佐酰胺;Azosemide Other Names： Azosemide;SK 110;PLE 1053;Diart;Luret CAS： 27589-33-9 Formula： C₁₂H₁₁ClN₆O₂S₂ Mole Weight： 370.84147 structure： Company： Roche (Originator), Sanofi-synthélabo (Licensee) Usage： Diuretics, RENAL-UROLOGIC DRUGS 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. Intermediates: Serial 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. Intermediates: Serial 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.