ALX-0646(free base), ALX-646CL
Chemical Name: N,N-Dimethyl-N-[2-[5-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-3-yl]ethyl]amine dihydrochloride
CAS No. 251967-66-5, 208464-98-6 (benzoate), 208464-67-9 (free base), 208464-99-7 (fumarate), 208464-97-5 (oxalate), 208464-96-4 (succinate)
项目整合开发状态: Phase I
项目研究机构: NPS Pharmaceuticals (Originator)
合成路线:Condensation between 5-bromoindole (I) in ether and oxalyl chloride (II) in dichloromethane followed by treatment with dimethylamine provides N,N-dimethyaminoglyoxyl derivative (III),which is then reduced with LiAlH4 in THF to yield compound (IV).Coupling of (IV) with benzoyl chloride (V) by means of Et3N and DMAP in dichloromethane affords benzoylindole derivative (VI),which is then subjected to reaction with tributylstannyl derivative (VII) in toluene in the presence of Pd(PPh3)4 to furnish compound (VIII).Treatment of (VIII) with NaOH in refluxing MeOH gives indole (IX),which is converted into the final product by reduction with LiAlH4 in refluxing THF) and treatment with HCl for the formation of the corresponding hydrochloride salt.Alternatively,the target compound can be obtained as follows: treatment of (IV) with KH in ether and tert-butyllithium in pentane followed by reaction with N-methylpiperidinone (X) affords hydroxy derivative (XI),which is finally converted into the desired product.
📌 参考资料/链接：
参考文献标题:5-Cyclo indole cpds.as 5-HT1D receptor ligands
文献作者:Slassi,A.; Edwards,L.; Meng,Q.; Rakhit,S.(NPS Allelix Corp.)
参考来源:EP 0944595; JP 2001504501; WO 9823587
📄 详细内容
合成路线:Condensation between 5-bromoindole (I) in ether and oxalyl chloride (II) in dichloromethane followed by treatment with dimethylamine provides N,N-dimethyaminoglyoxyl derivative (III),which is then reduced with LiAlH4 in THF to yield compound (IV).Coupling of (IV) with benzoyl chloride (V) by means of Et3N and DMAP in dichloromethane affords benzoylindole derivative (VI),which is then subjected to reaction with tributylstannyl derivative (VII) in toluene in the presence of Pd(PPh3)4 to furnish compound (VIII).Treatment of (VIII) with NaOH in refluxing MeOH gives indole (IX),which is converted into the final product by reduction with LiAlH4 in refluxing THF) and treatment with HCl for the formation of the corresponding hydrochloride salt.Alternatively,the target compound can be obtained as follows: treatment of (IV) with KH in ether and tert-butyllithium in pentane followed by reaction with N-methylpiperidinone (X) affords hydroxy derivative (XI),which is finally converted into the desired product.
参考文献标题:5-Cyclo indole cpds.
文献作者:Rakhit,S.; Edwards,L.; Slassi,A.; Meng,Q.(NPS Allelix Corp.)
参考来源:US 5998438
合成路线:Condensation between 5-bromoindole (I) in ether and oxalyl chloride (II) in dichloromethane followed by treatment with dimethylamine provides N,N-dimethyaminoglyoxyl derivative (III),which is then reduced with LiAlH4 in THF to yield compound (IV).Coupling of (IV) with benzoyl chloride (V) by means of Et3N and DMAP in dichloromethane affords benzoylindole derivative (VI),which is then subjected to reaction with tributylstannyl derivative (VII) in toluene in the presence of Pd(PPh3)4 to furnish compound (VIII).Treatment of (VIII) with NaOH in refluxing MeOH gives indole (IX),which is converted into the final product by reduction with LiAlH4 in refluxing THF) and treatment with HCl for the formation of the corresponding hydrochloride salt.Alternatively,the target compound can be obtained as follows: treatment of (IV) with KH in ether and tert-butyllithium in pentane followed by reaction with N-methylpiperidinone (X) affords hydroxy derivative (XI),which is finally converted into the desired product.
参考文献标题:5-Bicyclopiperidinetryptamine derivatives as selective 5-HT1D agonists
文献作者:Arora,J.; et al.
参考来源:Soc Neurosci Abst 2000,26(Part 1),Abst 145.14
产品链接: CAS No.208464-67-9››