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Eletriptan, UK-116044-04(HBr salt), UK-116044, Relpax

依来曲普坦Chemical Name: 5-[2-(Benzenesulfonyl)ethyl]-3-[1-methylpyrrolidin-2(R)-ylmethyl]-1H-indole
CAS No. 143322-58-1, 143577-61-1 (hemisuccinate), 179041-30-6 (monofumarate), 177834-92-3 (monoHBr salt), 180637-87-0 (monosuccinate)
项目整合开发状态: Launched-2001
项目研究机构: Pfizer (Originator)
合成路线:The reaction of N-(benzyloxycarbonyl)-D-proline (I) with oxalyl chloride in dichloromethane/DMF gives the corresponding acyl chloride (II),which is condensed with 5-bromoindole (III) by means of ethylmagnesium bromide in ether yielding 3-(N-benzyloxycarbonyl-D-prolyl)-5-bromoindole (IV).The reduction of the carbonyl group of (IV) with LiAlH4 in THF affords 5-bromo-3-[1-methylpyrrolidin-2(R)-ylmethyl]indole (V),which is condensed with phenyl(vinyl)sulfone (VI) by means of tri-p-tolylphosphine,palladium acetate and triethylamine in refluxing acetonitrile giving the substituted (E)-vinyl sulfone (VII).Finally,this compound is hydrogenated with H2 over Pd/C in ethanol/HCl.
📌 参考资料/链接:
参考文献标题:Indole derivs
文献作者:Macor,J.E.; Wythes,M.J.(Pfizer Inc.)
参考来源:EP 0592438; JP 1993507288; JP 1997003063; US 5545644; WO 9206973

📄 详细内容


合成路线:The reaction of N-(benzyloxycarbonyl)-D-proline (I) with oxalyl chloride in dichloromethane/DMF gives the corresponding acyl chloride (II),which is condensed with 5-bromoindole (III) by means of ethylmagnesium bromide in ether yielding 3-(N-benzyloxycarbonyl-D-prolyl)-5-bromoindole (IV).The reduction of the carbonyl group of (IV) with LiAlH4 in THF affords 5-bromo-3-[1-methylpyrrolidin-2(R)-ylmethyl]indole (V),which is condensed with phenyl(vinyl)sulfone (VI) by means of tri-p-tolylphosphine,palladium acetate and triethylamine in refluxing acetonitrile giving the substituted (E)-vinyl sulfone (VII).Finally,this compound is hydrogenated with H2 over Pd/C in ethanol/HCl.

参考文献标题:Salts of an anti-migraine indole deriv
文献作者:Harding,V.D.; Macrae,R.J.; Ogilvie,R.J.(Pfizer Inc.)
参考来源:EP 0776323; JP 1997512283; US 6110940; WO 9606842


合成路线:The reaction of N-(benzyloxycarbonyl)-D-proline (I) with oxalyl chloride in dichloromethane/DMF gives the corresponding acyl chloride (II),which is condensed with 5-bromoindole (III) by means of ethylmagnesium bromide in ether yielding 3-(N-benzyloxycarbonyl-D-prolyl)-5-bromoindole (IV).The reduction of the carbonyl group of (IV) with LiAlH4 in THF affords 5-bromo-3-[1-methylpyrrolidin-2(R)-ylmethyl]indole (V),which is condensed with phenyl(vinyl)sulfone (VI) by means of tri-p-tolylphosphine,palladium acetate and triethylamine in refluxing acetonitrile giving the substituted (E)-vinyl sulfone (VII).Finally,this compound is hydrogenated with H2 over Pd/C in ethanol/HCl.

参考文献标题:Process for the preparation of 3-acyl-indoles
文献作者:Perkins,J.F.(Pfizer Inc.)
参考来源:EP 1088817


合成路线:The reaction of N-(benzyloxycarbonyl)-D-proline (I) with oxalyl chloride in dichloromethane/DMF gives the corresponding acyl chloride (II),which is condensed with 5-bromoindole (III) by means of ethylmagnesium bromide in ether yielding 3-(N-benzyloxycarbonyl-D-prolyl)-5-bromoindole (IV).The reduction of the carbonyl group of (IV) with LiAlH4 in THF affords 5-bromo-3-[1-methylpyrrolidin-2(R)-ylmethyl]indole (V),which is condensed with phenyl(vinyl)sulfone (VI) by means of tri-p-tolylphosphine,palladium acetate and triethylamine in refluxing acetonitrile giving the substituted (E)-vinyl sulfone (VII).Finally,this compound is hydrogenated with H2 over Pd/C in ethanol/HCl.
参考文献标题:Eletriptan
文献作者:Ngo,J.; Rabasseda,X.; Castar,J.
参考来源:Drugs Fut 1997,22(3),221


产品链接: CAS No. 143322-58-1››