【药物名称】Alfuzosin hydrochloride, SL-77499(free base), SL-7749910, Xatral OD, Xatral Retard, Xatral XL, Xatral SR, Alfetim, Uroxatral, Urion, Alfoten, Xatral
化学结构式(Chemical Structure):
参考文献No.61928
标题:Alfuzosin hydrochloride
作者:Cazor, J.L.; Borg, F.; Dimsdale, M.
来源:Drugs Fut 1986,11(10),821
合成路线图解说明:

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.

参考文献No.84643
标题:Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives
作者:Manoury, P.M.; Binet, J.L.; Dumas, A.P.; Lefevre-Borg, F.; Cavero, I.
来源:J Med Chem 1986,2919-25
合成路线图解说明:

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.

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