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  • 1484-84-0,C7H15NO,129.2037,2-(2-piperidinyl)-1-ethanol; 2-Pi--药物合成数据库
  • 发布时间:2004-10-25 来源:本站整理
  • 【化学名】
    2-(2-piperidinyl)-1-ethanol; 2-Piperidineethanol
    【CAS登记号】
    1484-84-0
    【结构式】
    1484-84-0,C7H15NO,129.2037,2-(2-piperidinyl)-1-ethanol; 2-Pi--药物合成数据库
    【分子式】
    C7H15NO
    【分子量】
    129.2037
    【来源】
    Acros Organics; Aldrich; ICN Biomedical Research Products; INSPEC Group PLC & Int'l Specialty Chemicals Ltd; Interchem Corp.; Interor; Koei Chemical Company, Ltd; Pfaltz & Bauer, Inc.; Raschig GmbH; Reilly Industries, Inc.; Sichuan Sangao Biochemical Co., Ltd.; TCI
    【合成情况】
     
    〖目标产物〗
    Tiquizium bromide, HSR-902, Thiaton
    〖合成路线〗
    〖合成方法〗
    The reaction of 2-piperidineethanol (I) with acrylonitrile (II) gives N-(2-cyanoethyl)piperidine-2-ethanol (III), which by treatment with SOCl2 is converted into the chloronitrile (IV). The cyclization of (IV) with NaH affords 3-cyanoquinolizidine (V), which by hydrolysis with ethanol and HCl yields ethyl quinolizidine-3-carboxylate (VI). The Grignard reaction of (VI) with 2-thienylmagnesium bromide gives thienyl-3-quinolizidinyl methanol (VIII), which is dehydrated with HCl ethanol to afford 3-(di-2-thienylmethylene)quinolizidine (IX). Finally, this compound is quaternirzed with methyl bromide in acetone.
    〖参考〗
    Blancafort, P.; Serradell, M.N.; Casta馿r, J.; Thorpe, P.J.; Tiquizium bromide. Drugs Fut 1982, 7, 9, 655
    〖目标产物〗
    Tiquizium bromide, HSR-902, Thiaton
    〖合成路线〗
    〖合成方法〗
    The reaction of 2-piperidineethanol (I) with acrylonitrile (II) gives N-(2-cyanoethyl)piperidine-2-ethanol (III), which by treatment with SOCl2 is converted into the chloronitrile (IV). The cyclization of (IV) with NaH affords 3-cyanoquinolizidine (V), which by hydrolysis with ethanol and HCl yields ethyl quinolizidine-3-carboxylate (VI). The Grignard reaction of (VI) with 2-thienylmagnesium bromide gives thienyl-3-quinolizidinyl methanol (VIII), which is dehydrated with HCl ethanol to afford 3-(di-2-thienylmethylene)quinolizidine (IX). Finally, this compound is quaternirzed with methyl bromide in acetone.
    〖参考〗
    Ogawa, N.; Matsubara, I.; Kato, H.; Kurata, S.; Koshinaka, E.; Yamagishi, K.; Kubo, S.; Studies on antispasmodics. I. Synthesis and anticholinergic activity of 1-, 2- and 3-diarylmethylenequinolizidine quaternary ammonium salts. Chem Pharm Bull 1979, 27, /div> d
    〖目标产物〗
    Tiquizium bromide, HSR-902, Thiaton
    〖合成路线〗
    〖合成方法〗
    The reaction of 2-piperidineethanol (I) with acrylonitrile (II) gives N-(2-cyanoethyl)piperidine-2-ethanol (III), which by treatment with SOCl2 is converted into the chloronitrile (IV). The cyclization of (IV) with NaH affords 3-cyanoquinolizidine (V), which by hydrolysis with ethanol and HCl yields ethyl quinolizidine-3-carboxylate (VI). The Grignard reaction of (VI) with 2-thienylmagnesium bromide gives thienyl-3-quinolizidinyl methanol (VIII), which is dehydrated with HCl ethanol to afford 3-(di-2-thienylmethylene)quinolizidine (IX). Finally, this compound is quaternirzed with methyl bromide in acetone.
    〖参考〗
    Kato, H.; Koshinaka, E.; Ogawa, N.; Kurata, S.; Yamagishi, K.; Ishikuza, M. (Hokuriku Seiyaku Co., Ltd.); Substituted quinolizidine and indolizidine derivatives and the preparation thereof. BE 0866988; DE 2820687; FR 2390956; GB 1602927; JP 8034148
    〖目标产物〗
    FK-453, FR-453, FR-113453
    〖合成路线〗
    〖合成方法〗
    A new synthesis of FK-453 has been published: The cyclization of 1-aminopyridinium iodide (I) with 3-phenylpropynoic acid ethyl ester (II) by means of KOH in DMF gives 2-phenylpyrazolo[1,5-a]pyridine-3-carboxylic acid ethyl ester (III), which is decarboxylated with 47% aqueous HBr yielding 2-phenylpyrazolo[1,5-a]pyridine (IV). The Vilsmayer formylation of (IV) with POCl3 and DMF affords 2-phenylpyrazolo[1,5-a]pyridine-3-carbaldehyde (V), which by a Horner-Emmonds condensation with 2-(diethoxyphosphoryl)acetic acid ethyl ester and NaH in THF is converted into 3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-2(E)-propenoic acid ethyl ester (VII). The hydrolysis of (VII) with NaOH in methanol gives the free acid (VIII), which by reaction with SOCl2 in dichloromethane yields the corresponding acyl chloride (IX). The condensation of (IX) with 2-(2-hydroxyethyl)piperidine (X) by means of triethylamine in dichloromethane affords FK-453 as a racemic mixture (XI), which is finally submitted to optical resolution.
    〖参考〗
    Kita, Y.; Akahane, A.; Kusunoki, T.; Terai, T.; Yoshida, K.; Shiokawa, Y.; Mitsunaga, T.; Katayama, H.; Discovery of FK453, a novel non-xanthine adenosine A1 receptor antagonist. Bioorg Med Chem Lett 1996, 6, 17, 2059
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