新产品编号:158709

合成路线:An alternative process consisted in the palladium-catalyzed condensation of iodoaniline (VIII) with the acyl silane (XV),to produce the 2-silyl indole (XVI).Then,acid desilylation of (XVI),followed by treatment with oxalic acid yielded the title compound.

合成路线:An alternative procedure for the synthesis of indolylpropanol (VII) is depicted as follows: alkylation of 2-trimethylsilyl-1,3-dithiane (IX) with bromide (X) employing n-butyllithium in cold THF afforded (XI).Subsequent hydrolysis of the thioacetal group of (XI) by means of HgO/HgCl2 provided acylsilane (XII).Iodoaniline (XIII) was prepared by iodination of p-triazolylaniline (IV) with iodine monochloride.Condensation of iodoaniline (XIII) with acylsilane (XII) in the presence of Pd(OAc)2 produced the silylated indole (XIV).Then acid treatment of (XIV) removed both silyl groups to give (VII).

合成路线:In an alternative method,the title compound was obtained by desilylation of the 2-silylindole precursor (XXI).

参考文献标题:Palladium catalyzed indolization
文献作者:Chen,C.-Y.; Larsen,R.D.(Merck & Co.,Inc.)
参考来源:US 5808064; WO 9806725


合成路线:Hydrogenation of the enantiomerically pure 1-(alpha-methylbenzyl)-3-(hydroxymethyl)pyrrolidine (I) in the presence of Pearlman's catalyst and di-tert-butyl dicarbonate produced the N-Boc pyrrolidine (II).Reaction of (II) with methanesulfonyl chloride,followed by condensation of the resulting mesylate (III) with (S)-alpha-methylbenzylamine (IV) in toluene at 150 C in a sealed tube afforded the aminomethyl pyrrolidine derivative (V).Then,acidic cleavage of the Boc protecting group yielded pyrrolidine (VI).

合成路线:Halogenation of the substituted aniline (VII) by means of iodine monochloride gave ortho-iodoaniline (VIII).3-Butyn-1-ol (IX) was protected as the 1,4-bis(triethylsilyl)derivative (X) by deprotonation with butyllithium,followed by treatment with triethylsilyl chloride.Palladium-catalyzed condensation of disilylated butynol (X) with iodoaniline (VIII) furnished a mixture of the bis(silylated) tryptophol (XI) and the O-desilylated analogue (XII).Treatment of the crude mixture with methanolic HCl produced the completely desilylated indole (XIII),which was converted to mesylate (XIV) by reaction with methanesulfonyl chloride and triethylamine.Alkylation of pyrrolidine (VI) with mesylate (XIV) then yielded the target (indolylethyl)pyrrolidine,which was finally converted to the title dioxalate salt.
参考文献标题:Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1-yl)ethyl]indoles: Potent agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B receptor
文献作者:Sternfeld,F.; Guiblin,A.R.; Jelley,R.A.; Matassa,V.G.; Reeve,A.J.; Hunt,P.A.; Beer,M.S.; Heald,A.; Stanton,J.A.; Sohal,B.; Watt,A.P.; Street,L.J.
参考来源:J Med Chem 1999,42(4),677