2-(2-piperidinyl)-1-ethanol; 2-Piperidineethanol -Drug Synthesis Database

【结构式】

【分子编号】17614

【品名】2-(2-piperidinyl)-1-ethanol; 2-Piperidineethanol

【CA登记号】1484-84-0

【分子式】C₇H₁₅NO

【分子量】129.20224

【元素组成】C 65.07% H 11.7% N 10.84% O 12.38%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

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.

参考文献中间体

合成目标

【1】 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, 6, 1454-63.
【2】 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 .
【3】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Thorpe, P.J.; Tiquizium bromide. Drugs Fut 1982, 7, 9, 655.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	17614	2-(2-piperidinyl)-1-ethanol; 2-Piperidineethanol	1484-84-0	C₇H₁₅NO	详情	详情
(II)	10847	Acrylonitrile	107-13-1	C₃H₃N	详情	详情
(III)	32078	3-[2-(2-hydroxyethyl)-1-piperidinyl]propanenitrile		C₁₀H₁₈N₂O	详情	详情
(IV)	32079	3-[2-(2-chloroethyl)-1-piperidinyl]propanenitrile		C₁₀H₁₇ClN₂	详情	详情
(V)	32080	octahydro-2H-quinolizine-3-carbonitrile		C₁₀H₁₆N₂	详情	详情
(VI)	32081	ethyl octahydro-2H-quinolizine-3-carboxylate		C₁₂H₂₁NO₂	详情	详情
(VII)	32082	bromo(2-thienyl)magnesium	5713-61-1	C₄H₃BrMgS	详情	详情
(VIII)	32083	octahydro-2H-quinolizin-3-yl[di(2-thienyl)]methanol		C₁₈H₂₃NOS₂	详情	详情
(IX)	32084	3-[di(2-thienyl)methylene]octahydro-2H-quinolizine		C₁₈H₂₁NS₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

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.

参考文献中间体

合成目标

【1】 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.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	32760	1-aminopyridinium iodide		C₅H₇IN₂	详情	详情
(II)	13278	ethyl phenylpropiolate; ethyl 3-phenyl-2-propynoate	2216-94-6	C₁₁H₁₀O₂	详情	详情
(III)	13279	ethyl 2-phenylpyrazolo[1,5-a]pyridine-3-carboxylate		C₁₆H₁₄N₂O₂	详情	详情
(IV)	13280	2-Phenylpyrazolo[1,5-a]pyridine		C₁₃H₁₀N₂	详情	详情
(V)	13271	2-Phenylpyrazolo[1,5-a]pyridine-3-carbaldehyde		C₁₄H₁₀N₂O	详情	详情
(VI)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(VII)	13283	ethyl (E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-2-propenoate		C₁₈H₁₆N₂O₂	详情	详情
(VIII)	13274	(E)-3-(2-Phenylpyrazolo[1,5-a]pyridin-3-yl)-2-propenoic acid		C₁₆H₁₂N₂O₂	详情	详情
(IX)	13275	(E)-3-(2-Phenylpyrazolo[1,5-a]pyridin-3-yl)-2-propenoyl chloride		C₁₆H₁₁ClN₂O	详情	详情
(X)	17614	2-(2-piperidinyl)-1-ethanol; 2-Piperidineethanol	1484-84-0	C₇H₁₅NO	详情	详情
(XI)	13287	(E)-1-[2-(2-Hydroxyethyl)-1-piperidinyl]-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-2-propen-1-one		C₂₃H₂₅N₃O₂	详情	详情

Extended Information