• 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:
    : A process for preparing therapeutically active compounds comprising preparation of a Wittig reagent and employing it in a reaction according to the reaction scheme: NaOCH3 Ph3PO
    公开号:SU923366A3
    申请号:SU792798502
    申请日:1979-08-03
    公开日:1982-04-23
    发明作者:Бамберг Петер
    申请人:Астра Лэкемедель Аб (Инофирма)；
    IPC主号:
    专利说明:

    The invention relates to an improved method for producing Ν, Ν-dimethyl-3 ”(4-bromophenyl) ~ 3“ (3-pyridyl) allylamine of the formula 1
    or its dihydrochloride, or Z-isomer, which has valuable pharmaceutical properties.
    A known method of producing Ν, Ν-dimethyl-3 ”(4-bromophenyl) -3 ~ (3-pyridyl) allylamine, which consists in the fact that c> -dimethylamino-4-bromopropiophenone is reacted with pyridyllithium obtained by the interaction of n-butyllithium with 3-bromopyridine, and obtained in stage 1- (4-bromophenyl) -3 ”(Ν, N-dimethylamino) -1- (3 - pyridyl) propanol is subjected to dehydrogenation, followed by isolation of the target product in free form, in the form of a salt or Z-isomer (1).
    The disadvantage of this method is that the yield of the target product does not exceed 2.5%, in terms of the starting material brompropiophenone or bromopyridine.
    (A The aim of the invention is to increase the yield of the target product.
    This goal is achieved by the method of producing Ν, N-dimethyl-3 “(4-bromophenyl) -3“ (Z-pyridyl) allylamine, 15 or its dihydrochloride, or Z-isomer, which consists in the fact that Z-pyridyl-4-bromophenylketone subjected to interaction with the compound of the formula T1 ® CH E θ 20 pBTSB g CH g I ^ · 1g (m)
    CH 3 J where ph means' phenyl, in the presence of sodium methylate or butyllithium .thenium, followed by isolation of the ce923366 left product in free form or in the form of di hydrochloride, or Z-isomer.
    Example 1. Obtaining N, N-dimethyl-3 * (4-bromophenyl “3“ (3-pyridyl) allylamine di hydrochloride.
    A suspension of 1.4 g (2.5 mol) of dimethylaminoethyl triphenylphosphonium bromide in 2 ml of dimethylformamide is added to 0.14 g (2.5 mol) of sodium methylate in 1 ml of dimethylformamide. After stirring for 10 minutes, 0.66 g (2.5 mmol) of 3 ~ pyridyl-4-bromophenyl-ketone in 2 ml of dimethylformamide are added. A brown solution forms. The mixture was stirred at room temperature overnight and then poured into ice water. An oily residue was extracted with ether. The ether phase is washed with water and evaporated. The residue was stirred with a mixture of ether and petroleum ether (1: 2). In this case, triphenylphosphine oxide crystallizes. The crystals are filtered and the mother liquor is evaporated. The residue was extracted twice with 10 ml of hexane and 1 ml of concentrated hydrochloric acid was added to the hexane solution. Two phases form. Then, a mixture of ethanol and ether (1: 1) was added dropwise to obtain a homogeneous phase. Then the product crystallizes.
    After cooling, 0.3 g (40%, in terms of the initial ketone) of the product is obtained with mp. 188-192 ° C.
    Example 2. Obtaining Ν, Ν-dimethyl _ 3 “(4-bromophenyl) -3“ (3 - pyridyl) ki over magnesium sulfate and evaporation of the ether phase give 2.2 g (69%) of the desired product as a yellow oil (mixture isomers of Z and E in a ratio of 5 62:38).
    Example 3. To a solution of 2.2 g of the base analogously to example 2 in 20 ml of acetone add 1 ml (11 mol) of concentrated hydrochloric acid 10. The reaction mixture was refluxed for 30 minutes, then cooled, acetone was decanted off from the precipitate, and recrystallization from isopropanol gave 15.1.2 g (30%) of N, N-dimethyl-3 “(4-bromophenyl) -3 ~ dihydrochloride monohydrate - (3 ~ pyridyl) allylamine as an isomer Z having a melting point of 192- * 194 ° C.
    The proposed method allows to increase the yield of the target product to 30-69%.
    权利要求:
    Claims (1)
    [1]
    Claim
    The method of obtaining N, Ν-dimethyl-Z - (4-bromophenyl) -3 _ (3pyridyl) allyl
    CH 3 35 or its di hydrochloride, or Z-isomer, characterized in that allylamine.
    10 mol of butyllithium in 10 ml of hexane is added to 4.14 g (10 moles of dimethylaminoethyltriphenylphosphonium bromide 40 at room temperature for one minute. After stirring for 30 minutes, a suspension of v of 2.62 g (10 mol) of 3 “pyridyl-4- bromfenilketona in 15 ml of dry tetrahydro-5 furan. The reaction mixture was heated to 6D ° C for 5 hours. After cooling, 25 ml of 2M hydrochloric acid, washed with toluene, tetrahydrofuran was evaporated in vacuo, 50 again added 2M hydrochloric acid, the aqueous phase washed with toluene twice m, filtered and alkalinized. The aqueous phase is extracted twice with ether. After drying, in order to increase the yield of the target product, 3-pyridyl-4-bromophenylketone is reacted with a compound of the formula I Ο Θ Br where ph is phenyl in the presence of sodium methylate or butyl lithium, followed by isolation of the target product in free form or in the form of dihydrochloride, or the Z-isomer.
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    同族专利:
    公开号 | 公开日
    NO782304L|1979-01-05|
    FI64581C|1983-12-12|
    IT1105226B|1985-10-28|
    SE7707707L|1979-01-05|
    IT7850123D0|1978-06-30|
    AT365171B|1981-12-28|
    SE409861B|1979-09-10|
    DK295378A|1979-01-05|
    WO1979000023A1|1979-01-25|
    JPS5414976A|1979-02-03|
    CH641163A5|1984-02-15|
    ES471302A1|1979-09-01|
    FI64581B|1983-08-31|
    CA1082198A|1980-07-22|
    FI782115A|1979-01-05|
    ATA483778A|1981-05-15|
    NL7807246A|1979-01-08|
    引用文献:
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    SE7909514L|1979-11-16|1981-05-17|Astra Laekemedel Ab|NEW HALOPHENYL-PYRIDYL-ALLYLAMINE DERIVATIVES|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    SE7707707A|SE409861B|1977-07-04|1977-07-04|A NEW PROCEDURE FOR PREPARING A THERAPEUTIC ACTIVE PYRIDINE ASSOCIATION|
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