[2-(4-Methyl-2-phenylpiperazino)-3-pyridinyl]methanol -Drug Synthesis Database

【结构式】

【分子编号】10320

【品名】[2-(4-Methyl-2-phenylpiperazino)-3-pyridinyl]methanol

【CA登记号】61337-89-1

【分子式】C₁₇H₂₁N₃O

【分子量】283.37336

【元素组成】C 72.06% H 7.47% N 14.83% O 5.65%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XIII)

Two new syntheses of labeled azamianserin have been described: 1) [13C]-Labeled: The reaction of 2-chloropyridine-3-carbonitrile (I) with glycine ethyl ester (II) by means of Na2CO3 in DMSO gives N-(3-cyanopyridin-2-yl)glycine ethyl ester (III), which by reaction with methylamine in toluene is converted into the corresponding amide (IV). The treatment of (IV) with sodium hypophosphite and RaNi in water-acetic acid-pyridine affords N-(3-formylpyridin-2-yl)glycine methylamide (V), which is reduced with NaBH4 in methanol to the corresponding alcohol (VI). Further reduction of (VI) with LiAlH4 in refluxing dioxane gives 2-[2-(methylamino)ethylamino]-3-pyridinemethanol (VII), which is condensed with [13C]-labeled alpha-bromoacetophenone (VIII) [prepared from labeled benzene (IX) submitted to a Friedel-Crafts condensation with AlCl3 and acetic anhydride to acetophenone (X) and bromination with Br2 in ether] by means of triethylamine in dioxane to afford the substituted acetophenone (XI). The cyclization of (XI) by heating at 120 C yields the tricyclic compound (XII), which is reduced with LiAlH4 - AlCl3 in ethyl ether to give 2-(4-methyl-2-phenylpiperazin-1-yl)pyridine-3-methanol (XIII). Finally, this compound is cyclized in hot H2SO4.

参考文献中间体

合成目标

【1】 Wieringa, J.H.; Kaspersen, F.M.; van Rooij, F.A.M.; Sperling, E.G.M.; The synthesis of ORG 3770 labelled with 3H, 13C and 14C. J Label Compd Radiopharm 1989, 27, 9, 1055.

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)	10308	2-Chloronicotinonitrile; 2-Chloro-3-cyanopyridine	6602-54-6	C₆H₃ClN₂	详情	详情
(II)	10309	ethyl 2-aminoacetate; Glycine ethyl ester	459-73-4	C₄H₉NO₂	详情	详情
(III)	10310	ethyl 2-[(3-cyano-2-pyridinyl)amino]acetate		C₁₀H₁₁N₃O₂	详情	详情
(IV)	10311	2-[(3-Cyano-2-pyridinyl)amino]-N-methylacetamide		C₉H₁₀N₄O	详情	详情
(V)	10312	2-[(3-Formyl-2-pyridinyl)amino]-N-methylacetamide		C₉H₁₁N₃O₂	详情	详情
(VI)	10313	2-[[3-(Hydroxymethyl)-2-pyridinyl]amino]-N-methylacetamide		C₉H₁₃N₃O₂	详情	详情
(VII)	10314	(2-[[2-(Methylamino)ethyl]amino]-3-pyridinyl)methanol		C₉H₁₅N₃O	详情	详情
(VIII)	10315	2-Bromo-1-phenyl-ethanone; 2-Bromo-1-phenyl-1-ethanone	70-11-1	C₈H₇BrO	详情	详情
(VIII)	44642	2-bromo-1-phenyl-1-ethanone		C₈H₇BrO	详情	详情
(IX)	13364	Benzene	71-43-2	C₆H₆	详情	详情
(IX)	44640	benzene		C₆H₆	详情	详情
(X)	10317	Acetophenone	98-86-2	C₈H₈O	详情	详情
(X)	44641	acetophenone		C₈H₈O	详情	详情
(XI)	10318	2-[(2-[[3-(Hydroxymethyl)-2-pyridinyl]amino]ethyl)(methyl)amino]-1-phenyl-1-ethanone		C₁₇H₂₁N₃O₂	详情	详情
(XI)	44643	2-[(2-[[3-(hydroxymethyl)-2-pyridinyl]amino]ethyl)(methyl)amino]-1-phenyl-1-ethanone		C₁₇H₂₁N₃O₂	详情	详情
(XII)	10319	8-Methyl-6a-phenyl-7,8,9,10-tetrahydro-5H,6aH-pyrazino[2,1-b]pyrido[2,3-d][1,3]oxazine		C₁₇H₁₉N₃O	详情	详情
(XII)	44644	8-methyl-6a-phenyl-7,8,9,10-tetrahydro-5H,6aH-pyrazino[2,1-b]pyrido[2,3-d][1,3]oxazine		C₁₇H₁₉N₃O	详情	详情
(XIII)	10320	[2-(4-Methyl-2-phenylpiperazino)-3-pyridinyl]methanol	61337-89-1	C₁₇H₂₁N₃O	详情	详情
(XIII)	44645	[2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinyl]methanol		C₁₇H₂₁N₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

2) [14C]-Labeled: The condensation of 2-chloro-3-nitropyridine (I) with 1-methyl-3-phenylpiperazine (II) by means of KF at 140 C in DMF gives 4-methyl-1-(3-nitropyridin-2-yl)-2-phenylpiperazine (III), which is reduced with H2 over Pd/C in ethanol to the amine (IV). The reaction of (IV) with pentyl nitrite and bromoform at 100 C yields 1-(3-bromopyridin-2-yl)-4-methyl-2-phenylpiperazine (V), which by reaction with butyllithium and [14C]-labeled CO2 in ether is converted into 2-(4-methyl-2-phenylpiperazin-1-yl)pyridine-3-carboxylic acid (VI). The reduction of (VI) with LiAlH4 in hot THF affords the corresponding alcohol (VII), which is finally cyclized in hot H2SO4.

参考文献中间体

合成目标

【1】 Wieringa, J.H.; Kaspersen, F.M.; van Rooij, F.A.M.; Sperling, E.G.M.; The synthesis of ORG 3770 labelled with 3H, 13C and 14C. J Label Compd Radiopharm 1989, 27, 9, 1055.

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)	10321	2-Chloro-3-nitropyridine	5470-18-8	C₅H₃ClN₂O₂	详情	详情
(II)	10322	1-Methyl-3-phenylpiperazine	5271-27-2	C₁₁H₁₆N₂	详情	详情
(III)	10323	4-Methyl-1-(3-nitro-2-pyridinyl)-2-phenylpiperazine		C₁₆H₁₈N₄O₂	详情	详情
(IV)	10324	2-(4-Methyl-2-phenylpiperazino)-3-pyridinamine; 2-(4-Methyl-2-phenylpiperazino)-3-pyridinylamine		C₁₆H₂₀N₄	详情	详情
(V)	10325	1-(3-Bromo-2-pyridinyl)-4-methyl-2-phenylpiperazine		C₁₆H₁₈BrN₃	详情	详情
(VI)	10326	2-(4-Methyl-2-phenylpiperazino)nicotinic acid		C₁₇H₁₉N₃O₂	详情	详情
(VI)	44646	2-(4-methyl-2-phenyl-1-piperazinyl)nicotinic acid		C₁₇H₁₉N₃O₂	详情	详情
(VII)	10320	[2-(4-Methyl-2-phenylpiperazino)-3-pyridinyl]methanol	61337-89-1	C₁₇H₂₁N₃O	详情	详情
(VII)	44647	[2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinyl]methanol		C₁₇H₂₁N₃O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Reaction of 2-chloronicotinonitrile (I) with 1-methyl-3-phenylpiperazine (II) gives 2-(4-methyl-2-phenyl-1-piperazinyl)-3-pyridinecarbonitrile (III), which is hydrolyzed to the carboxylic acid, which is reducted to the hydroxymethyl derivative (IV). Cyclization of (IV) in concentrated sulfuric acid at 20-35 C gives the title compound after 2 h and treatment with ammonia.

参考文献中间体

合成目标

【1】 Van der Burg, W.J. (Akzo Nobel N.V.); Tetracyclic compounds. BE 0840362; CH 622261; DE 2614406; DK 142498; ES 446634; FR 2305986; GB 1543171; JP 76122099; NL 754075 .
【2】 Koch, H.; Azamianserin. Drugs Fut 1985, 10, 12, 965.

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)	10308	2-Chloronicotinonitrile; 2-Chloro-3-cyanopyridine	6602-54-6	C₆H₃ClN₂	详情	详情
(II)	10322	1-Methyl-3-phenylpiperazine	5271-27-2	C₁₁H₁₆N₂	详情	详情
(III)	29819	2-(4-methyl-2-phenyl-1-piperazinyl)nicotinonitrile		C₁₇H₁₈N₄	详情	详情
(IV)	10320	[2-(4-Methyl-2-phenylpiperazino)-3-pyridinyl]methanol	61337-89-1	C₁₇H₂₁N₃O	详情	详情

Extended Information