• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Prepn. of 2-(2- and 3-thienyl)ethylamines of formula (I) is claimed (where R1 is in posn. 2, 3, 4 or 5 and is H, alkyl, aromatic gp. which may be a heterocycle (and is opt. mono- or poly-substd. by alkyl, phenyl, halogen, nitro, cyano, amino, carboxy or alkoxy), alkoxy, halogen, nitro, carboxy, cyano or amino; the aminoethyl chain may occupy posn. 2 or 3; R2 is H, alkyl or atomatic gp. which may be a heterocycle (and may be substd. as above); Ar is aromatic gp. which may be a heterocycle (and may be substd. as above)). Process comprises (a) heating (V) to give (VI); (b) treating with water to give (VII); (c) reducing to give (VIII); (d) reacting this with a base, followed by a halogen deriv. Ar-CH(Hal)-R2 to give (X) and (e) treatment of (X) with acid to give (I) (where X and Y are alkyl, aryl, alkoxy, aryloxy, dialkyl- or diarylamino; M is a cation, pref. alkali or alkaline earth metal). (I) are intermediates for chemical prods. and pharmaceuticals.
    公开号:SU1181543A3
    申请号:SU823456110
    申请日:1982-06-25
    公开日:1985-09-23
    发明作者:Шекрун Исаак；Эймес Ален
    申请人:Санофи (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a process for the creep of 2- (thienyl-2) or 2- (thienyl-3) ethylamine derivatives, which are used as intermediates in the chemical-pharmaceutical industry. The purpose of the invention is to simplify the process of synthesizing 2- (thienyl-2) or 2-hthiensh 1-3 derivatives of ethylamine. Example 1. Preparation of H-ortho-chlorobenzyl-2- (thienyl-2) ethylamine hydrochloride rata. Option A. Stadi A. Dietsh1-N- (thienylidene-2) aminomethylphosphonate. To 16.7 g (0, 1 mol) of diethylaminomethylphosphonate in 200 ml of absolute ethanol was added 11.2 g (0.1 mol) of 2-thienaldehyde and boiled under reflux for 30 minutes. The water formed during the reaction is then removed by azeotropic distillation. After complete evaporation of the solvent, 28 g (100%) of pure yellow oil are obtained. IR spectrum (film),. 1645 () {1260 (P-0); 1060-1080 (P-O-C) Nuclear Magnetic Resonance Spectrum (CDCEj), CL (tMS), ppm: 1.3 (triplet, 6H); 3.9-4.45 (multiplet, 6H); 7-7.6 (multiplet, 3N); 8.5 (doublet, 1H), Stage B and B, Diethyl- / g- (thienyl-2 N-vinylphosphoramidate, K suspension 11.2 g (0.1 mol) tert, potassium butylate in 160 MP THF (tetrahydrofuran) a solution of 27.9 g (0.1 mol) of diethyl-H- (thienylidene-2) aminomethylphosphonate in 40 ml of THF is added dropwise. During the addition, the temperature varies from 20 to 35 ° C. After the addition is completed, the temperature for 30 the min is swept up to 40-45 ° С, after which the reaction mixture is drunk in 400 MP of an aqueous saturated solution of ammonium chloride, the aqueous phase is extracted with diisopropyl ether, then the combined ether phases washed with a saturated solution of sodium chloride, dried with sodium sulfate and evaporated to obtain 20.9 g (75%) of the product indicated as a yellow oil as a yellow oil; NMR spectrum (CDCtj), cL (TMS), m, d, 1.3 ( triplet, 6H); 3.95 (double doublet, 4H); 6.35 (multiplet, 1H); 6.9-7.5 (multiplet, 5H) after exchange with DjO (multiplet, 4H), 1 32 IR spectrum (film), (NH) 3300; 1650 (); 1250 (P-0); 1050 (P-O-C), Stage G, Diethyl-M-2- (thienyl-2) ethylphosphoramidate. The resulting 20.9 g (0.075 mol) of DIETH-y9- (thienyl-2) N-vinylphosphoramidate is added to a solution of 2.85 g (0.075 mol) of sodium borohydride in 200 mp of ethanol. During the addition process the temperature rises, then stabilizes (/ - AOC) After additional stirring for 2 hours, the temperature of the medium was adjusted to 45-50 ° C for 1 hour, then the ethanol was evaporated and the residue was treated with a mixture of diisopropyl ether and water. The aqueous phase is re-extracted several times with diisopropyl ether and the combined organic phases are washed with water, dried with sodium sulfate and evaporated to give 21 g (75% of the original aminomethylphosphonate) of the title product as a yellow oil, IR spectrum (film), 3400; 1520; 1275; 1210, NMR spectrum (CASEH), cG (TMS), m, d,: 1.3 (triplet, 6H); 3.1 (multiplet, 5H; A - CH CHj-NH), 3.1 is obtained by exchange with DjO (multiplet, 4H); 4.05 (double doublet, 4H); 6.75-7.2 (multiplet, ZN) ,. Stage D, Diethyl-K-orthochlorobenzyl-L-2- (thienyl-2) ethylphosphoramidate, To a suspension of 3.6 g (0.075 mol) of sodium hydride (50% in oil) in 150 MP of toluene is added dropwise at stirring at room temperature 21 g (0.075 mol) of ethyl TH2- (thienyl-2) ethylphosphoramidate in 20 ml of toluene. The medium that has become red is brought to a temperature of 80 ° C over 1 h, then 16.1 g (0.1 mol) of orthochlorobenzyl chloride is added dropwise. The temperature is maintained at 80 ° C with stirring for 3 hours, then after cooling it is washed with water, the Toluene phase is then evaporated to obtain the title phosphoramidate (contaminated with excess orthochlorobenzyl chloride) as an oil, used without purification in the next stage. A clean sample is obtained by chromatography silica column (eluted with ethyl acetate), IR spectrum (film), cm: 3000; 1550; 1250 1050.
    权利要求:
    Claims (2)
    [1]
    1. METHOD FOR PRODUCING 2- (THienyl-2) -i or 2- (thienyl-3) ethylamine derivatives of the formula [GZ- ^ C ^ MHC ^ -Sbshchs! .
    iro) 2 p-nhch = ch - {Rj | (IV) where R - has the indicated meaning, which is then reduced with sodium borohydride to a compound of the general formula, characterized in that, in order to simplify the process, a carbanion of the general formula.
    (R0) 2 pnhch 2 ch 2 -CP) (v) where R is the indicated value, it is subsequently reacted with sodium hydride in toluene and halobenzyl chloride to obtain the general formula of the compound e m® (RO) oP-CH-N = CH II about where R is alkyl with 1-4 carbon atoms;
    M + - alkali metal cation, by heating at 35-45 ° C in tetrahydrofuran is converted to a derivative of the general formula (RO) 2 PN-CH 2 CH 2 -JFj]
    About CH 2 SbH 5 (VI) where R and M + have the indicated meanings, the latter is converted by the action of water into a compound of the general formula where R - has the indicated meaning, followed by treatment with acid.
    [2]
    2. The method of pop. 1, characterized in that the compound of general formula (IV) is directly reacted with an alkali metal tert-butylate M + in tetrahydrofuran at 35-45 ° C, then with halobenzyl chloride and sodium borohydride and the resulting compound of general formula (VI) is treated with an acid.
    SU, „> 1181543
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    同族专利:
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    EP0253595A3|1986-07-16|1988-12-14|COOKSON GROUP plc|Novel pyrrole monomers and polymers prepared therefrom|
    FR2624860B1|1987-12-18|1990-06-01|Sanofi Sa|PROCESS FOR THE PREPARATION OF N- -2 ETHYLAMINE|
    US4900539A|1988-12-22|1990-02-13|The United States Of America As Represented By The United States Department Of Energy|Radiohalogenated thienylethylamine derivatives for evaluating local cerebral blood flow|
    US7820180B2|2004-09-24|2010-10-26|The Trustees Of The University Of Pennsylvania|Listeria-based and LLO-based vaccines|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    FR8113064A|FR2508455B1|1981-06-30|1981-06-30|
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