SUN-N8075
Chemical Name: 1-(4-Amino-2,3,5-trimethylphenoxy)-3-[4-[4-(4-fluorobenzyl)phenyl]piperazin-1-yl]propan-2(S)-ol dimethanesulfonate
CAS No. 224450-56-0, 224450-44-6 (free base)
项目整合开发状态: Phase I
项目研究机构: Daiichi Suntory Pharma (Originator), Taisho (Licensee)
合成路线:Chemoselective protection of the amino group of 2,3,5-trimethyl-4-aminophenol (I) with di-tert-butyl dicarbonate (Boc)2O in THF gives compound (II),which is then treated with NaH and (S)-glycidyl 3-nitrobenzenesulfonate (III) to yield epoxypropane (IV).On the other hand,treatment of 4,4'-difluorobenzophenone (V) with piperazine (VI) in acetonitrile in the presence of Et3N gives derivative (VII),which is reduced with Et3siH in the presence of H2SO4 and TFA to afford piperazine (VIII).Condensation of epoxypropane (IV) with piperazine (VIII) in refluxing 2-propanol furnishes compound (IX),which is finally converted into the desired product by first removal of the Boc group by exposure to TFA in CH2Cl2,followed by treatment with methanesulfonic acid (MeSO3H).
📌 参考资料/链接：
参考文献标题:Arylpiperidinopropanol and arylpiperazinopropanol derivs.and pharmaceuticals containing the same
文献作者:Nakanishi,K.; Annoura,H.; Tamura,S.(Suntory Ltd.)
参考来源:CA 2276373; EP 0958280; WO 9923072
📄 详细内容
合成路线:Chemoselective protection of the amino group of 2,3,5-trimethyl-4-aminophenol (I) with di-tert-butyl dicarbonate (Boc)2O in THF gives compound (II),which is then treated with NaH and (S)-glycidyl 3-nitrobenzenesulfonate (III) to yield epoxypropane (IV).On the other hand,treatment of 4,4'-difluorobenzophenone (V) with piperazine (VI) in acetonitrile in the presence of Et3N gives derivative (VII),which is reduced with Et3siH in the presence of H2SO4 and TFA to afford piperazine (VIII).Condensation of epoxypropane (IV) with piperazine (VIII) in refluxing 2-propanol furnishes compound (IX),which is finally converted into the desired product by first removal of the Boc group by exposure to TFA in CH2Cl2,followed by treatment with methanesulfonic acid (MeSO3H).
参考文献标题:Discovery of (2S)-1-(4-amino-2,3,5-trimethylphenoxy)-3-(4-[4-(4-fluorobenzyl)phenyl)-1-piperazinyl)-2-propanol dimethanesulfonate (SUN N8075): A dual Na+ and Ca2+ channel blocker with antioxidant activity
文献作者:Annoura,H.; Nakanishi,K.; Toba,T.; Takemoto,N.; Imajo,S.; Miyajima,A.; Tamura-Horikawa,Y.; Tamura,S.
参考来源:J Med Chem 2000,43(18),3372
产品链接: CAS No. 224450-56-0››