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【结 构 式】 
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【分子编号】27575 【品名】butyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-[(2S)-3-hydroxy-2-methylpropyl]-4-methoxyphenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate 【CA登记号】 |
【 分 子 式 】C35H43NO6 【 分 子 量 】573.72956 【元素组成】C 73.27% H 7.55% N 2.44% O 16.73% |
合成路线1
该中间体在本合成路线中的序号：(XXIX)Addition of Grignard reagent (XXIV) to this aldehyde (XXIII) at -78 C produced the diastereomeric mixture of alcohols (XXV), which was oxidized to ketone (XXVI) with tetrapropylammonium perruthenate (TPAP) and N-methylmorpholine N-oxide. The tert-butyl ester group of (XXVI) was then transesterified with n-butanol and Ti(OBu)4 to ester (XXVII). Cyclization of ketoester (XXVII) was performed in the presence of lithium hexamethyldisilazide to produce the cyclopentapyridine system (XXVIII). This mixture of tertiary alcohols was deoxygenated with triethylsilane and a Lewis acid to yield (XXIX) as the major diastereoisomer.
| 【1】 Frey, L.F.; Devine, P.N.; Tschaen, D.M.; Dolling, U.H.; Tillyer, R.D.; Kato, Y. (Banyu Pharmaceutical Co., Ltd.; Merck & Co., Inc.); Stereoselective deoxygenation reaction. EP 0923557; JP 1999514676; WO 9806700 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIII) | 27569 | tert-butyl (3R)-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]-3-(6-butyl-3-formyl-2-pyridinyl)propanoate | C34H53NO5Si | 详情 | 详情 | |
| (XXIV) | 27570 | 1,3-benzodioxol-5-yl(bromo)magnesium | C7H5BrMgO2 | 详情 | 详情 | |
| (XXV) | 27571 | tert-butyl (3R)-3-[3-[1,3-benzodioxol-5-yl(hydroxy)methyl]-6-butyl-2-pyridinyl]-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]propanoate | C41H59NO7Si | 详情 | 详情 | |
| (XXVI) | 27572 | tert-butyl (3R)-3-[3-(1,3-benzodioxol-5-ylcarbonyl)-6-butyl-2-pyridinyl]-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]propanoate | C41H57NO7Si | 详情 | 详情 | |
| (XXVII) | 27573 | butyl (3R)-3-[3-(1,3-benzodioxol-5-ylcarbonyl)-6-butyl-2-pyridinyl]-3-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]propanoate | C41H57NO7Si | 详情 | 详情 | |
| (XXVIII) | 27574 | butyl (6S,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-((2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropyl)-4-methoxyphenyl]-5-hydroxy-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate | C41H57NO7Si | 详情 | 详情 | |
| (XXIX) | 27575 | butyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-[(2S)-3-hydroxy-2-methylpropyl]-4-methoxyphenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate | C35H43NO6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIX)Oxidation of the side-chain hydroxyl group of (XXIX) to the carboxylic acid (XXXI) was effected in a two-step procedure involving SO3-pyridine complex oxidation to aldehyde (XXX), followed by oxidation to carboxylic acid (XXXI) with sodium chlorite. Finally, basic hydrolysis of the butyl ester of (XXXI) provided the target compound.
| 【1】 Frey, L.F.; Devine, P.N.; Tschaen, D.M.; Dolling, U.H.; Tillyer, R.D.; Kato, Y. (Banyu Pharmaceutical Co., Ltd.; Merck & Co., Inc.); Stereoselective deoxygenation reaction. EP 0923557; JP 1999514676; WO 9806700 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIX) | 27575 | butyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[2-[(2S)-3-hydroxy-2-methylpropyl]-4-methoxyphenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate | C35H43NO6 | 详情 | 详情 | |
| (XXX) | 27576 | butyl (5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-2-butyl-7-[4-methoxy-2-[(2S)-2-methyl-3-oxopropyl]phenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate | C35H41NO6 | 详情 | 详情 | |
| (XXXI) | 27577 | (2S)-3-[2-[(5S,6R,7R)-5-(1,3-benzodioxol-5-yl)-6-(butoxycarbonyl)-2-butyl-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl]-5-methoxyphenyl]-2-methylpropionic acid | C35H41NO7 | 详情 | 详情 |