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【结 构 式】 
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【分子编号】16168 【品名】2-(3-pyridinyl)acetic acid; 3-Pyridylacetic acid 【CA登记号】501-81-5 |
【 分 子 式 】C7H7NO2 【 分 子 量 】137.13812 【元素组成】C 61.31% H 5.14% N 10.21% O 23.33% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of 2,6-di-tert-butyllphenol (I) with hexamethylenetetramine (HMT) and sulfuric acid in ethyleneglycol at 130 C gives 4-hydroxy-3,5-di-tert-butylbenzaldehyde (II), which is finally condensed with 2-(3-pyridyl)acetic acid (III) by means of piperidine in dichloromethane at 130 C.
| 【1】 Lazer, E.S.; Farina, P.R.; Gundel, R.H.; Wegner, C.D.; 2,6-Disubstituted-4-(2-arylethenyl)phenol 5-lipoxygenase inhibitors: Development and profile of BI-L-239. Drugs Fut 1991, 16, 7, 641. |
| 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) | 25925 | 2,6-di(tert-butyl)phenol | 128-39-2 | C14H22O | 详情 | 详情 |
| (II) | 14875 | 3,5-Bis(1,1-dimethylethyl)-4-hydroxybenzaldehyde; 3,5-di(tert-butyl)-4-hydroxybenzaldehyde; 3,5-Di-tert-butyl-4-hydroxybenzaldehyde | 1620-98-0 | C15H22O2 | 详情 | 详情 |
| (III) | 16168 | 2-(3-pyridinyl)acetic acid; 3-Pyridylacetic acid | 501-81-5 | C7H7NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Risedronic acid is prepared by treatment of 2-(3-pyridyl)acetic acid (I) with a mixture of phosphorous acid and phosphorus oxychloride at reflux for 2.5 h.
| 【1】 Benedict, J.J.; Perkins, C.M. (The Procter & Gamble Co.); Pharmaceutical compsns. containing geminal diphosphonates. AU 8551534; EP 0186405; ES 8707543; JP 1995285976; JP 1997202794; US 5583122 . |
| 【2】 Mealy, N.; Castaner, J.; Prous, J.; Risedronate Sodium. Drugs Fut 1993, 18, 7, 605. |
合成路线3
该中间体在本合成路线中的序号：(X)Removal of the desosamine unit was effected by hydrolysis in 1N HCl at r.t. The resulting diol (VIII) was then selectively acetylated at the 2'-hydroxyl yielding monoacetate ester (IX). Further coupling of (IX) with 3-pyridylacetic acid-HCl (X) was carried out by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) or, alternatively, by previous activation of (X) as the mixed anhydride with pivalic acid to furnish the 3-O-pyridylacetyl ester (XI). The protecting acetate group of (XI) was finally removed by selective hydrolysis in boiling MeOH.
| 【1】 Morimoto, S.; Sugiyama, H.; Tanikawa, T.; Kashimura, M.; Asaka, T.; Suzuki, K.; Adachi, T.; Akashi, T.; Synthesis and antibacterial activitis of unique acyclides: 3-O-Acyl-5-O-desosaminylerythronolide 6,9;11,12-dicarbonates. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F2160. |
| 【2】 Asaka, T.; Tanikawa, T.; Ishii, T.; Kashimura, M. (Taisho Pharmaceutical Co., Ltd.); Erythromycin A derivs.. WO 9813373 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 33091 | (2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione; (2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione | C39H65NO15 | 详情 | 详情 | |
| (VIII) | 33093 | (2S,3R,7R,8R,11R,12S,13S,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-hydroxy-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione | C31H51NO12 | 详情 | 详情 | |
| (IX) | 33094 | (2S,3R,4S,6R)-4-(dimethylamino)-2-[[(2S,3R,7R,8R,11R,12S,13S,14R,15R,19R)-8-ethyl-12-hydroxy-2,7,11,13,15,19-hexamethyl-5,10,17-trioxo-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icos-14-yl]oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate | C33H53NO13 | 详情 | 详情 | |
| (X) | 16168 | 2-(3-pyridinyl)acetic acid; 3-Pyridylacetic acid | 501-81-5 | C7H7NO2 | 详情 | 详情 |
| (XI) | 33095 | (2S,3R,7R,8R,11R,12S,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-2,7,11,13,15,19-hexamethyl-5,10,17-trioxo-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icos-12-yl 2-(3-pyridinyl)acetate; (2S,3R,7R,8R,11R,12S,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-2,7,11,13,15,19-hexamethyl-5,10,17-trioxo-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icos-12-yl 2-(3-pyridinyl)acetate | C40H58N2O14 | 详情 | 详情 |