Mizolastine, MKC-431, SL-85.0324, Zolistam, Zolistan, Mizolen, Zolim, Mizollen-药物合成数据库

【药物名称】Mizolastine, MKC-431, SL-85.0324, Zolistam, Zolistan, Mizolen, Zolim, Mizollen

化学结构式(Chemical Structure):

参考文献No.	6014
标题:	EP 217700, FR 2587029, JP 87061979, US 4820710
作者:	Manoury, P.; Binet, J.; Defosse, G. (Sanofi-Synth閘abo )
来源:	EP 0217700; FR 2587029; JP 1987061979; US 4820710

合成路线图解说明: Mizolastine can be obtained by two related ways: 1) The condensation of 2-chloro-1-(4-fluorobenzyl)benzimidazole (I) with N-(4-piperidyl)carbamic acid ethyl ester (II) by means of NaOCH3 at 14 C gives N-[1-[1-(4-fluorobenzyl)benzimidazol-2-yl]piperidin-4-yl]carbamic acid ethyl ester (III), which is methylated with methyl iodide and NaH in DMF to yield the corresponding N-methyl derivative (IV). The decarboxylative hydrolysis of (IV) with 48% HBr in acetic acid affords N-[1-[1-(4-fluorobenzyl)benzimidazol-2-yl]piperidin-4-yl]-N-methylamine (V), which is finally condensed with 2-(methylsulfanyl)pyrimidin-4(3H)-one (VI) by heating at 170 C. 2) Compound (V) can also be obtained by direct condensation of 2-chloro-1-(4-fluorobenzyl)benzimidazole (I) with 4-(methylamino)piperidine (VII) by means of K2CO3 in refluxing isoamyl alcohol.

参考文献No.	368281
标题:	Mizolastine
作者:	Mealy, N.; Ngo, J.; Casta馿r, J.
来源:	Drugs Fut 1996,21(8),799

合成路线图解说明: Mizolastine can be obtained by two related ways: 1) The condensation of 2-chloro-1-(4-fluorobenzyl)benzimidazole (I) with N-(4-piperidyl)carbamic acid ethyl ester (II) by means of NaOCH3 at 14 C gives N-[1-[1-(4-fluorobenzyl)benzimidazol-2-yl]piperidin-4-yl]carbamic acid ethyl ester (III), which is methylated with methyl iodide and NaH in DMF to yield the corresponding N-methyl derivative (IV). The decarboxylative hydrolysis of (IV) with 48% HBr in acetic acid affords N-[1-[1-(4-fluorobenzyl)benzimidazol-2-yl]piperidin-4-yl]-N-methylamine (V), which is finally condensed with 2-(methylsulfanyl)pyrimidin-4(3H)-one (VI) by heating at 170 C. 2) Compound (V) can also be obtained by direct condensation of 2-chloro-1-(4-fluorobenzyl)benzimidazole (I) with 4-(methylamino)piperidine (VII) by means of K2CO3 in refluxing isoamyl alcohol.