【结 构 式】 |
【药物名称】CD-3127, LG-268, LG-100268 【化学名称】6-[1-(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopropyl]pyridine-3-carboxylic acid 【CA登记号】153559-76-3 【 分 子 式 】C24H29NO2 【 分 子 量 】363.50423 |
【开发单位】Ligand (Originator) 【药理作用】Antidiabetic Drugs, Atherosclerosis Therapy, CARDIOVASCULAR DRUGS, ENDOCRINE DRUGS, Lipoprotein Disorders, Treatment of , METABOLIC DRUGS, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, ABCA1 Expression Enhancers, Insulin Sensitizers, Retinoid RXR Agonists |
合成路线1
The Friedel Crafts condensation of 2,5-dichloro-2,2,5,5-tetramethylhexane (I) with toluene (II) by means of AlCl3 gives 1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene (III), which is submitted to a new condensation with the pyridine-2-carbonyl chloride (IV) by means of AlCl3 in dichloromethane to yield the diaryl ketone (V). The reaction of (V) with methyltriphenylphosphonium bromide (VI) and NaNH2 affords the 1,1-diarylethylene (VII), which is treated with Et2Zn and Cl-CH2-I in dichloromethane to provide the 1,1-diarylcyclopropane (VIII). Finally, the ester group of (VIII) is hydrolyzed with KOH in methanol/water to yield the target carboxylic acid.
【1】 Faul, M.M.; Ratz, A.M.; Sullivan, K.A.; Trankle, W.G.; Winneroski, L.L.; Synthesis of novel retinoid X receptor-selective retinoids. J Org Chem 2001, 66, 17, 5772. |
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) | 35216 | 2,5-dichloro-2,5-dimethylhexane | C8H16Cl2 | 详情 | 详情 | |
(II) | 12890 | Toluene | 108-88-3 | C7H8 | 详情 | 详情 |
(III) | 35217 | 1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene | C15H22 | 详情 | 详情 | |
(IV) | 64262 | methyl 6-(chlorocarbonyl)nicotinate | C8H6ClNO3 | 详情 | 详情 | |
(V) | 64263 | methyl 6-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]nicotinate | C23H27NO3 | 详情 | 详情 | |
(VI) | 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 |
(VII) | 64264 | methyl 6-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)vinyl]nicotinate | C24H29NO2 | 详情 | 详情 | |
(VIII) | 64265 | methyl 6-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)cyclopropyl]nicotinate | C25H31NO2 | 详情 | 详情 |