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【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
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