2-amino-3-pyridinol; 2-Amino-3-hydroxypyridine -Drug Synthesis Database

【结构式】

【分子编号】37086

【品名】2-amino-3-pyridinol; 2-Amino-3-hydroxypyridine

【CA登记号】16867-03-1

【分子式】C₅H₆N₂O

【分子量】110.11552

【元素组成】C 54.54% H 5.49% N 25.44% O 14.53%

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：(III)

By cyclization of 2-amino-3-benzyloxypyridine (I) with 3-chloro-4-oxopentanonitrile (II) by means of thiethylamine in ethanol. Compound (I) is prepared by benzylation of 2-amino-3-hydroxypyridine (III) with benzyl chloride (IV) by means of NaOH in water-CH2Cl2. Compound (II) is prepared by chlorination of 4-oxopentanonitrile (V) with SO2Cl2 in ether.

参考文献中间体

合成目标

【1】 Puchalski, C.; Bristol, J.A.; EP 0033094 .
【2】 Hillier, K.; Serradell, M.N.; Castaner, J.; Blancafort, P.; SCH-28,080. Drugs Fut 1982, 7, 10, 755.

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)	37087	3-(benzyloxy)-2-pyridinylamine; 3-(benzyloxy)-2-pyridinamine	24016-03-3	C₁₂H₁₂N₂O	详情	详情
(II)	37089	3-chloro-4-oxopentanenitrile		C₅H₆ClNO	详情	详情
(III)	37086	2-amino-3-pyridinol; 2-Amino-3-hydroxypyridine	16867-03-1	C₅H₆N₂O	详情	详情
(IV)	19171	1-(Chloromethyl)benzene; Benzyl chloride	100-44-7	C₇H₇Cl	详情	详情
(V)	37088	4-oxopentanenitrile		C₅H₇NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

1-(3-Hydroxy-2-pyridyl)pyrrole (III) was prepared by Paal-Knorr condensation of 2-amino-3-hydroxypyridine (I) with 2,5-dimethoxytetrahydrofuran (II). The O-alkylation of (II) with ethyl alpha-bromophenylacetate (IV) in the presence of NaH in THF furnished ether (V). Subsequent saponification of the ethyl ester group of (IV) gave rise to carboxylic acid (VI), that was cyclized to tricyclic ketone (VII) upon treatment with phosphorus pentachloride. Finally, alkylation of the corresponding potassium enolate of (VII) with ethyl iodide yielded the title compound.

参考文献中间体

合成目标

【1】 Morelli, E.; Campiani, G.; Fabbrini, M.; et al.; Pyrrolobenzoxazepinone derivatives as non-nucleoside HIV-1 RT inhibitors: Further structure-activity relationship studies and identification of more potent broad-spectrum HIV-1 RT inhibitors with antiviral activirty. J Med Chem 1999, 42, 21, 4462.

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)	37086	2-amino-3-pyridinol; 2-Amino-3-hydroxypyridine	16867-03-1	C₅H₆N₂O	详情	详情
(II)	12132	2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether	696-59-3	C₆H₁₂O₃	详情	详情
(III)	41979	2-(1H-pyrrol-1-yl)-3-pyridinol		C₉H₈N₂O	详情	详情
(IV)	41980	ethyl 2-bromo-2-phenylacetate	2882-19-1	C₁₀H₁₁BrO₂	详情	详情
(V)	41981	ethyl 2-phenyl-2-[[2-(1H-pyrrol-1-yl)-3-pyridinyl]oxy]acetate		C₁₉H₁₈N₂O₃	详情	详情
(VI)	41982	2-phenyl-2-[[2-(1H-pyrrol-1-yl)-3-pyridinyl]oxy]acetic acid		C₁₇H₁₄N₂O₃	详情	详情
(VII)	41983	6-phenylpyrido[3,2-b]pyrrolo[1,2-d][1,4]oxazepin-7(6H)-one		C₁₇H₁₂N₂O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

2-Amino-3-hydroxypyridine (I) is alkylated with N-(2-chloroethyl)piperidine (II) under phase transfer conditions to provide ether (III). Subsequent cyclization of aminopyridine (III) with bis-trichlorophenyl malonate (IV) in refluxing acetone leads to the pyridopyrimidine (V). This is finally condensed with the N-(bromomethyl)saccharin derivative (VI) to furnish the title compound.

参考文献中间体

合成目标

【1】 Hermecz, I.; Kapui, Z.; Arányi, P.; Bátori, S.; Varga, M.; Dessilla, S.; Lévai, F.; Mikus, E.; Pascal, M.; Simonot, B.; Urbán Szabó, K.; Vasváriné Debreczy, L.; T. Nagy, L. (Sanofi-Synthélabo); Saccharin derivs. as orally active elastase inhibitors. WO 0144245 .

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)	37086	2-amino-3-pyridinol; 2-Amino-3-hydroxypyridine	16867-03-1	C₅H₆N₂O	详情	详情
(II)	10117	1-(2-Chloroethyl)piperidine; N-(2-Chloroethyl)piperidine	1932-03-2	C₇H₁₄ClN	详情	详情
(III)	62082	3-[2-(1-piperidinyl)ethoxy]-2-pyridinamine; 3-[2-(1-piperidinyl)ethoxy]-2-pyridinylamine		C₁₂H₁₉N₃O	详情	详情
(IV)	12956	bis(2,4,6-trichlorophenyl) malonate		C₁₅H₆Cl₆O₄	详情	详情
(V)	62083	2-hydroxy-9-[2-(1-piperidinyl)ethoxy]-4H-pyrido[1,2-a]pyrimidin-4-one		C₁₅H₁₉N₃O₃	详情	详情
(VI)	62084	2-(bromomethyl)-4-isopropyl-6-methoxy-1H-1,2-benzisothiazole-1,1,3(2H)-trione		C₁₂H₁₄BrNO₄S	详情	详情

Extended Information