2-(4-Pyridinyl)-1-ethanol; 2-Pyridin-4-ylethanol -Drug Synthesis Database

【结构式】

【分子编号】52533

【品名】2-(4-Pyridinyl)-1-ethanol; 2-Pyridin-4-ylethanol

【CA登记号】

【分子式】C₇H₉NO

【分子量】123.1546

【元素组成】C 68.27% H 7.37% N 11.37% O 12.99%

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：(XXI)

The (S)-methyl tryptamine (XIII) was protected as the N-Boc derivative (XIV), and its ethyl ester group was then hydrolyzed with KOH to provide acid (XV). Coupling of (XV) with isoquinuclidine (XVI) in the presence of PyBOP gave amide (XVII). Cleavage of the N-Boc group of (XVII) was carried out employing trifluoroacetic acid in anisole. The resultant amine (XVIII) was condensed with 2,4-dinitrobenzenesulfonyl chloride (XIX) under modified Schotten-Baumann conditions to afford the sulfonamide (XX). Mitsunobu coupling of sulfonamide (XX) with 4-(2-hydroxyethyl)pyridine (XXI) gave adduct (XXII). The sulfonyl group of (XXII) was finally removed by treatment with neat propylamine to yield the title secondary amine.

参考文献中间体

合成目标

【1】 Ashton, W.T.; et al.; Orally, bioavailable, indole-based nonpeptide GnRH receptor antagonists with high potency and functional activity. Bioorg Med Chem Lett 2001, 11, 19, 2597.
【2】 Chu, L.; Wyvratt, M.J.; Ponpipom, M.M.; Lin, P.; Ashton, W.T.; Goulet, M.; Young, J.; Girotra, N.N.; Fisher, M.H. (Merck & Co., Inc.); Antagonists of gonadotropin releasing hormone. EP 1095038; WO 0004013 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIII)	52525	ethyl 2-[3-(2-amino-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropanoate	C₂₅H₃₂N₂O₂	详情	详情
(XIV)	52526	ethyl 2-[3-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1-methylethyl]-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropanoate	C₃₀H₄₀N₂O₄	详情	详情
(XV)	52527	2-[3-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-1-methylethyl]-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropanoic acid	C₂₈H₃₆N₂O₄	详情	详情
(XVI)	52528	2-azabicyclo[2.2.2]octane	C₇H₁₃N	详情	详情
(XVII)	52529	1,1-dimethylethyl 2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propylcarbamate	C₃₅H₄₇N₃O₃	详情	详情
(XVIII)	52530	2-[3-(2-amino-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1-(2-azabicyclo[2.2.2]oct-2-yl)-2-methyl-1-propanone	C₃₀H₃₉N₃O	详情	详情
(XIX)	52531	2,4-dinitrobenzenesulfonyl chloride	C₆H₃ClN₂O₆S	详情	详情
(XX)	52532	N-{2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propyl}-2,4-dinitrobenzenesulfonamide	C₃₆H₄₁N₅O₇S	详情	详情
(XXI)	52533	2-(4-Pyridinyl)-1-ethanol; 2-Pyridin-4-ylethanol	C₇H₉NO	详情	详情
(XXII)	52534	N-{2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]propyl}-2,4-dinitro-N-[2-(4-pyridinyl)ethyl]benzenesulfonamide	C₄₃H₄₈N₆O₇S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Alkylation of 2-pyridin-4-ylethanol (I) with 4-fluorobenzyl chloride (II), followed by reduction of the resultant pyridinium salt (III) with NaBH4 leads to the tetrahydropyridine (IV). Acid-catalyzed condensation of alcohol (IV) with benzhydrol (V) then provides the benzhydryl ether (VI) (1). Hydroboration of tetrahydropyridine (VI) and subsequent oxidative work up gives rise to the racemic trans piperidinol rac-(VII) (1,2). Resolution of (VII) is accomplished via esterification with (-)-camphanic chloride (VIII), followed by HPLC separation of the resulting diastereoisomers. The desired isomer (IX) is finally hydrolyzed employing K2CO3 in MeOH to provide the target enantiomer

参考文献中间体

合成目标

【1】 Ghorai, S.K.; Cook, C.; Davis, M.; Venkataraman, S.K.; George, C.; Beardsley, P.M.; Reith, M.E.A.; Dutta, A.K.; High affinity hydroxypiperidine analogues of 4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidine for the dopamine transporter: Stereospecific interactions in vitro and in vivo. J Med Chem 2003, 46, 7, 1220.
【2】 Dutta, A.K. (Wayne State University); N- and O-substd. 4-[2-(diphenylmethoxy)-ethyl]-1-[(phenyl)methyl]piperidine analogs and methods of treating CNS disorders therewith. WO 0198266 .

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)	52533	2-(4-Pyridinyl)-1-ethanol; 2-Pyridin-4-ylethanol		C₇H₉NO	详情	详情
(II)	12354	4-Fluorobenzyl chloride; 1-(Chloromethyl)-4-fluorobenzene	352-11-4	C₇H₆ClF	详情	详情
(III)	63533	1-[(4-fluorophenyl)methyl]-4-(2-hydroxyethyl)pyridinium chloride		C₁₄H₁₅ClFNO	详情	详情
(IV)	63534	2-{1-[(4-fluorophenyl)methyl]-1,2,3,6-tetrahydro-4-pyridinyl}-1-ethanol		C₁₄H₁₈FNO	详情	详情
(V)	11845	Diphenylmethanol; Benzhydrol	91-01-0	C₁₃H₁₂O	详情	详情
(VI)	63535	diphenylmethyl 2-{1-[(4-fluorophenyl)methyl]-1,2,3,6-tetrahydro-4-pyridinyl}ethyl ether; 4-{2-[(diphenylmethyl)oxy]ethyl}-1-[(4-fluorophenyl)methyl]-1,2,3,6-tetrahydropyridine		C₂₇H₂₈FNO	详情	详情
(VII)	63536	4-{2-[(diphenylmethyl)oxy]ethyl}-1-[(4-fluorophenyl)methyl]-3-piperidinol		C₂₇H₃₀FNO₂	详情	详情
(VIII)	16583	(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride; (-)-Camphanic chloride	39637-74-6	C₁₀H₁₃ClO₃	详情	详情
(IX)	63537	4-{2-[(diphenylmethyl)oxy]ethyl}-1-[(4-fluorophenyl)methyl]-3-piperidinyl 4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate		C₃₇H₄₂FNO₅	详情	详情

Extended Information