| Chemical Name： | (±)-N-[3-[(4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarboxamide monohydrochloride;(±)-N-[3-[(4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furamide monohydrochloride | | Generic Name： | 盐酸阿夫唑嗪;Alfuzosin hydrochloride | | Other Names： | Alfuzosin hydrochloride;SL-77499(free base);SL-7749910;Xatral OD;Xatral Retard;Xatral XL;Xatral SR;Alfetim;Uroxatral;Urion;Alfoten;Xatral | | CAS： | 81403-68-1 | | Related CAS： | 81403-80-7 (free base) | | Formula： | C19H28ClN5O4 | | Mole Weight： | 425.91911 | | structure： | | | Company： | Sanofi-synthélabo (Originator), Altana Pharma (Licensee), Lorex (Licensee) | | Usage： | Benign Prostatic Hyperplasia Therapy, RENAL-UROLOGIC DRUGS, Urologic Drugs, alpha1-Adrenoceptor Antagonists | | | |
| Route 1 | Title compound can be prepared as follows:1) 6,7-Dimethoxyquinazolin-2,4-dione (I) is converted to 2,4-dichloro 6,7-dimethoxyquinazoline (II), followed by selective displacement of the 4-chloro group with ammonia to give 4-amino-2-chloro-6,7-dimethoxyquinazoline (III).2) 3-(Methylamino)propanenitrile (IV) is reacted with the mixed anhydride obtained from tetrahydrofuran-2-carboxylic acid and ethyl chloroformate to form the amide (V), which on hydrogenation over rhodium at 80 C in the presence of ammonia affords the required secondary amine (VI) via rearrangement of the initially formed primary amine (VII). Condensation of amine (VI) with 4-amino-2-chloro-6,7-dimethoxyquinazoline (III) in refluxing amyl alcohol gives alfuzosin hydrochloride. | | | | Intermediates: | Serial No. | | N-[(2R,3R,4R,5S,6R)-2-(1-ethylpropoxy)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]acetamide | (III) | | methyl (2S,3R)-3-hydroxy-2-[(1R)-1-hydroxy-2-propenyl]-2,4-dimethyl-4-pentenoate | (I) | | methyl (2S,3S)-3-hydroxy-2-[(1R)-1-hydroxy-2-propenyl]-2,4-dimethyl-4-pentenoate | (II) | | methyl (4R,5R,6R)-4-isopropenyl-2,2,5-trimethyl-6-vinyl-1,3-dioxane-5-carboxylate | (IV) | | methyl (4R,5S,6R)-4-isopropenyl-2,2,5-trimethyl-6-vinyl-1,3-dioxane-5-carboxylate | (V) | | methyl (1S,2S,5R)-2,5-dihydroxy-1,3-dimethyl-3-cyclopentene-1-carboxylate | (VI) | | methyl (1R,2S,5R)-5-[[tert-butyl(dimethyl)silyl]oxy]-2-hydroxy-1,3-dimethyl-3-cyclopentene-1-carboxylate | (VII) | | | Reference 1: Binet, J.L.; Manoury, P.M.; Dumas, A.P.; Lefevre-Borg, F.; Cavero, I.; Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives. J Med Chem 1986, 29, 19-25. Reference 2: Cazor, J.L.; Borg, F.; Dimsdale, M.; Alfuzosin hydrochloride. Drugs Fut 1986, 11, 10, 821. | | | |
