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【结 构 式】 
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【分子编号】17491 【品名】ethyl acetate 【CA登记号】141-78-6 |
【 分 子 式 】C4H8O2 【 分 子 量 】88.10632 【元素组成】C 54.53% H 9.15% O 36.32% |
合成路线1
该中间体在本合成路线中的序号：(I)The condensation of ethyl acetate (I) with 4-picoline (II) by means of n-butyllithium in THF gives 1-(4-pyridyl)propanone (III), which by reaction with the dimethylacetal of dimethylformamide (IV) in refluxing HMPT is converted into 4-dimethylamino-3-(4-pyridyl)-3-buten-2-one (V). Finally, this compound is cyclized with cyanacetamide (VI) by means of sodium methoxide in refluxing DMF.
| 【1】 Lehser, G.Y.; Philion, R.E.; Page, D.F.; Opalka, C.J. (Sterling Winthrop Inc.); 5-(pyridinyl)-2(1H)-pyridinones, useful as cardiotonic agents and their preparation. DE 3044568; FR 2470124; GB 2065642; NL 8006399 . |
| 【2】 Serradell, M.N.; Castaner, J.; Blancafort, P.; WIN-47,203. Drugs Fut 1982, 7, 10, 757. |
| 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) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (II) | 31150 | 4-methylpyridine | 108-89-4 | C6H7N | 详情 | 详情 |
| (III) | 32092 | 1-(4-pyridinyl)acetone | C8H9NO | 详情 | 详情 | |
| (IV) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (V) | 32093 | (E)-4-(dimethylamino)-3-(4-pyridinyl)-3-buten-2-one | C11H14N2O | 详情 | 详情 | |
| (VI) | 12122 | Cyanoacetamide; 2-Cyanoacetamide | 107-91-5 | C3H4N2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)The condensation of 4-fluorocinnamic acid ethyl ester (I) with cyanacetic acid ethyl ester (II) by means of NaOEt in ethanol gives 2-cyano-3-(4-fluorophenyl)glutaric acid diethyl ester (III). Alternatively, glutarate (III) can also be obtained by condensation of 4-fluorobenzaldehyde (V) with cyanacetic ester (II) and acetic acid ethyl ester (VI). The reduction of the cyano group of (III) with H2 over PtO2 in ethanol, followed by cyclization in refluxing toluene, yields 4-(4-fluorophenyl)-6-oxopiperidine-3-carboxylic acid ethyl ester (IV) as a mixture of the cis- and trans-isomers. The reaction of the mixture (IV) with EtONa in refluxing toluene causes isomerization of the cis-isomer, affording (rac)-trans-4-(4-fluorophenyl)-6-oxopiperidine-3-carboxylic acid ethyl ester (VII), which is reduced with LiAlH4 or borane (NaBH4/BF3) to provide the (rac)-(trans)-hydroxymethylpiperidine (VIII). Finally, this compound is reductively methylated by treatment with formaldehyde and H2 over Pd/C in ethanol to furnish (rac)-(trans)-4-(4-fluorophenyl)-3-(hydroxymethyl)-1-methylpiperidine (IX), the desired intermediate. Alternatively, the cis/trans mixture 4-(4-fluorophenyl)-6-oxopiperidine-3-carboxylic acid ethyl ester (IV) can be methylated first with formaldehyde as before to give 4-(4-fluorophenyl)-1-methyl-6-oxopiperidine-3-carboxylic acid ethyl ester (X), also as a cis/trans mixture. This mixture is treated with EtONa in refluxing toluene to yield (rac)-(trans)-4-(4-fluorophenyl)-1-methyl-6-oxopiperidine-3-carboxylic acid ethyl ester (XI). Finally, this compound is reduced with LiAlH4 in THF/toluene to afford the previously described target intermediate (IX).
| 【1】 Bosch Rovira, A.; Dalmases Barjoan, P.; Herbera Espinal, M.R.; Carulla Oliver, J.M.; Marquillas Olóndriz, F. (Laboratorios Vita, SA); Process for obtaining (±)-trans-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine. ES 2121685 . |
| 【2】 Bosch Rovira, A.; Dalmases Barjoan, P.; Herbera Espinal, M.R.; Carulla Oliver, J.M.; Marquillas Olóndriz, F. (Laboratorios Vita, SA); Process for obtaining ethyl (±)-cis/(±)-trans-4-(4-fluorophenyl)-1-methylpiperidine-3-carboxylate. ES 2121684 . |
| 【3】 Bosch Rovira, A.; Dalmases Barjoan, P.; Marquilla Olondriz, F.; Herbera Espinal, M.R.; Carulla Oliver, J.M. (Laboratorios Vita, SA); Ethyl 4-(4-fluorophenyl)-2-piperidinone-5-carboxylate and process for obtaining it. ES 2121682 . |
| 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) | 56459 | ethyl (E)-3-(4-fluorophenyl)-2-propenoate | C11H11FO2 | 详情 | 详情 | |
| (II) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
| (III) | 56460 | diethyl 2-cyano-3-(4-fluorophenyl)pentanedioate | C16H18FNO4 | 详情 | 详情 | |
| (IV) | 56461 | ethyl 4-(4-fluorophenyl)-6-oxo-3-piperidinecarboxylate | C14H16FNO3 | 详情 | 详情 | |
| (V) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (VI) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (VII) | 56462 | ethyl (3S,4R)-4-(4-fluorophenyl)-6-oxo-3-piperidinecarboxylate | C14H16FNO3 | 详情 | 详情 | |
| (VIII) | 56463 | (rac)-[(3S,4R)-4-(4-fluorophenyl)piperidinyl]methanol | C12H16FNO | 详情 | 详情 | |
| (IX) | 43487 | [(3S,4R)-4-(4-fluorophenyl)-1-methylpiperidinyl]methanol; trans-(3S)-4-(4-fluorophenyl)-1-methyl-3-piperidine methanol | 105812-81-5 | C13H18FNO | 详情 | 详情 |
| (X) | 56464 | ethyl 4-(4-fluorophenyl)-1-methyl-6-oxo-3-piperidinecarboxylate | C15H18FNO3 | 详情 | 详情 | |
| (XI) | 56465 | ethyl (3S,4R)-4-(4-fluorophenyl)-1-methyl-6-oxo-3-piperidinecarboxylate | C15H18FNO3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)A new synthesis of BO-2727 has been described: The condensation of (2S,4R)-1-(tert-butoxycarbonyl)-4-(tert-butyldimethylsilyloxy)pyrrolidine-2-carbaldehyde (I) with ethyl acetate (II) by means of butyllithium and hexa-methyldisylazane (HMSA) in THF gives 3-[1-(tert-butoxycarbonyl)-4(R)-(tert-butyldimethylsilyloxy) pyrrolidin-2(S)-yl]-3-hydroxypropionic acid ethyl ester (III), which was submitted to column chromatography over silicagel yielding the pure 3(R)-hydroxypropionic acid (IV). The reduction of (IV) with NaBH4 in THF afforded the expected diol (V), which was treated with tosyl chloride and triethylamine to give the monotosylate (VI). The reaction of (VI) first with methylamine in methanol, and then with p-nitrobenzyloxycarbonyl chloride (PNZ-Cl) in the same solvent yielded (2S,4R)-2-[1(R)-hydroxy-3-[N-methyl-N-(p-nitrobenzyloxycarbonyl)amino]propyl] pyrrolidin-4-ol (VII). The reaction of (VII) first with SOCl2 and then with potassium thioacetate afforded the 4(R)-acetylsulfanyl derivative (VIII), which was hydrolyzed with NaOH in methanol/water to the corresponding thiol (IX). The condensation of (IX) with the carbapenem intermediate (X) by means of diisopropylethylamine (DIEA) in acetonitrile gave the precursor (protected) of BO-2727 (XI), which was finally deprotected by hydrogenation with H2 over Pd/C in THF/ethanol/pH-7 buffer.
| 【1】 Ohtake, N.; Okamoto, O.; Mitomo, R.; Kato, Y.; Yamamoto, K.; Haga, Y.; Fukatsu, H.; Nakagawa, S.; 1ß-Methyl-2-(5-substituted pyrrolidin-3-ylthio)carbapenems; 3. Synthesis and antibacterial activity of BO-2727 and its related compounds. J Antibiot 1997, 50, 7, 598. |
| 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) | 17490 | tert-butyl (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-formyl-1-pyrrolidinecarboxylate | C16H31NO4Si | 详情 | 详情 | |
| (II) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (III) | 17492 | tert-butyl (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(3-ethoxy-1-hydroxy-3-oxopropyl)-1-pyrrolidinecarboxylate | C20H39NO6Si | 详情 | 详情 | |
| (IV) | 17493 | tert-butyl (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-[(1R)-3-ethoxy-1-hydroxy-3-oxopropyl]-1-pyrrolidinecarboxylate | C20H39NO6Si | 详情 | 详情 | |
| (V) | 17494 | tert-butyl (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-[(1R)-1,3-dihydroxypropyl]-1-pyrrolidinecarboxylate | C18H37NO5Si | 详情 | 详情 | |
| (VI) | 17495 | tert-butyl (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-((1R)-1-hydroxy-3-[[(4-methylphenyl)sulfonyl]oxy]propyl)-1-pyrrolidinecarboxylate | C25H43NO7SSi | 详情 | 详情 | |
| (VII) | 16203 | 4-nitrobenzyl (2S,4R)-4-hydroxy-2-[(1R)-1-hydroxy-3-(methyl[[(4-nitrobenzyl)oxy]carbonyl]amino)propyl]-1-pyrrolidinecarboxylate | C24H28N4O10 | 详情 | 详情 | |
| (VIII) | 16204 | 4-nitrobenzyl (2S,4S)-4-(acetylsulfanyl)-2-[(1R)-1-hydroxy-3-(methyl[[(4-nitrobenzyl)oxy]carbonyl]amino)propyl]-1-pyrrolidinecarboxylate | C26H30N4O10S | 详情 | 详情 | |
| (IX) | 16205 | 4-nitrobenzyl (2S,4S)-2-[(1R)-1-hydroxy-3-(methyl[[(4-nitrobenzyl)oxy]carbonyl]amino)propyl]-4-sulfanyl-1-pyrrolidinecarboxylate | C24H28N4O9S | 详情 | 详情 | |
| (X) | 13224 | 4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 90776-59-3 | C29H27N2O10P | 详情 | 详情 |
| (XI) | 16207 | 4-nitrobenzyl (2S,4S)-4-([(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-2-[2-(4-nitrophenyl)acetyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]sulfanyl)-2-[(1R)-1-hydroxy-3-(methyl[[(4-nitrobenzyl)oxy]carbonyl]amino)propyl]-1-pyrrolidinecarboxylate | C41H44N6O14S | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)GW150526 was easily prepared starting from the known 3-unsubstituted indole derivative (IV) following the general synthetic route described in Scheme 20235901a. The known indole derivative (IV) was formylated at the C-3 position according to the well known Vilsmaier-Haack procedure obtaining the intermediate (VI) in high yield. The subsequent Wittig-type olefination reaction afforded the compound (VII) with high regio control in the formation of the olefinic moiety. The hydrolysis of the ethyl ester group afforded GV-150526 as sodium salt derivative.
| 【1】 Di Fabio, R.; Cugola, A.; Donati, D.; Ferinai, A.; Gaviraghi, G.; Ratti, E.; Trist, D.G.; Reggiani, A.; Identification and pharmacological characterization of GV150526, a novel glycine antagonist as potent neuroprotective agent. Drugs Fut 1998, 23, 1, 61. |
| 【2】 Salituro, F.G.; et al.; 3-(2-Carboxyindol-3-yl)propionic acid derivatives: Antagonists of the strychnine-insensitive glycine receptor associated with the N-methyl-D-aspartate receptor complex. J Med Chem 1990, 33, 11, 2946-8. |
| 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) | 28066 | 1-(3,5-dichlorophenyl)hydrazine | 39943-56-1 | C6H6Cl2N2 | 详情 | 详情 |
| (II) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (III) | 32141 | ethyl 2-[(E)-2-(3,5-dichlorophenyl)hydrazono]propanoate | C11H12Cl2N2O2 | 详情 | 详情 | |
| (IV) | 32142 | ethyl 4,6-dichloro-1H-indole-2-carboxylate | C11H9Cl2NO2 | 详情 | 详情 | |
| (V) | 32143 | N-methyl-N-phenylacetamide | 579-10-2 | C9H11NO | 详情 | 详情 |
| (VI) | 32144 | ethyl 4,6-dichloro-3-formyl-1H-indole-2-carboxylate | C12H9Cl2NO3 | 详情 | 详情 | |
| (VII) | 32145 | N-phenyl-2-(triphenylphosphoranylidene)acetamide | C26H22NOP | 详情 | 详情 | |
| (VIII) | 32147 | ethyl 3-[(E)-3-anilino-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate | C20H16Cl2N2O3 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)Alternatively, for the synthesis of analogues of GV-150526 substituted at the terminal phenyl ring belonging to the C-3 side chain as shown in Scheme 20235902a, compound (I) was transformed int the intermediate (III) in high yield. Following chemoselective deprotection of the tert-butyl ester group, the free carboxylic acid derivative (IV) was submitted to amidation reaction using different synthetic methods. In particular, the activation of the carboxy group through the formation of the corresponding 2-pyridyl thioester, generated in situ by the mild oxidation-reduction condensation reaction in the presence of 2,2'-dipyridyl disulfide and PPh3, was found to be highly efficient, also in the case of poor nucleophilic aromatic amines, affording the desired amide derivatives (VI) in high yield (either from the isolated 2-pyridyl thioester intermediate (V) or from the acid (IV) using a one pot procedure). Finally, target compounds were easily prepared by basic hydrolysis of the 2-carboxyethyl ester protecting group.
| 【1】 Struys, M.M.R.F.; et al.; Tetrahedron 1993, 49, 10, 2239. |
| 【2】 Davison, S.C.; et al.; VCH Publichers: Stuttgart 1989, 147, 4, 972-6. |
| 【3】 Di Fabio, R.; Cugola, A.; Donati, D.; Ferinai, A.; Gaviraghi, G.; Ratti, E.; Trist, D.G.; Reggiani, A.; Identification and pharmacological characterization of GV150526, a novel glycine antagonist as potent neuroprotective agent. Drugs Fut 1998, 23, 1, 61. |
| 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) | 28066 | 1-(3,5-dichlorophenyl)hydrazine | 39943-56-1 | C6H6Cl2N2 | 详情 | 详情 |
| (II) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (III) | 32141 | ethyl 2-[(E)-2-(3,5-dichlorophenyl)hydrazono]propanoate | C11H12Cl2N2O2 | 详情 | 详情 | |
| (IV) | 32142 | ethyl 4,6-dichloro-1H-indole-2-carboxylate | C11H9Cl2NO2 | 详情 | 详情 | |
| (V) | 32143 | N-methyl-N-phenylacetamide | 579-10-2 | C9H11NO | 详情 | 详情 |
| (VI) | 32144 | ethyl 4,6-dichloro-3-formyl-1H-indole-2-carboxylate | C12H9Cl2NO3 | 详情 | 详情 | |
| (VII) | 32145 | N-phenyl-2-(triphenylphosphoranylidene)acetamide | C26H22NOP | 详情 | 详情 | |
| (VIII) | 32147 | ethyl 3-[(E)-3-anilino-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate | C20H16Cl2N2O3 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：1) The condensation of 1-phenylhexan-3-one (I) with ethyl acetate by means of butyllithium and diisopropylamine in THF gives racemic 3-hydroxy-3-(2-phenylethyl)hexanoic acid ethyl ester (II), which is hydrolyzed with NaOH in methanol to the corresponding free acid (III). The optical resolution of (III) with (1R,2S)-(-)-norephedrine (IV) followed by treatment with aqueous HCl yields the chiral (R)-acid (V), which is treated with 4-biphenylyloxymethyl chloride (VI) and diisopropylethylamine in toluene affording the protected ester (VII). The reduction of the ester group of (VII) with diisobutylaluminum hydride (DIBAL) in toluene gives the monoprotected diol (VIII), which is oxidized at the primary hydroxy group with 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy radical (TEMPO) and NaOCl yielding the corresponding aldehyde (IX). The condensation of (IX) with (R)-3-(3-nitrophenyl)pentanoic acid methyl ester (X) by means of sodium hexamethyldisilazide (NaHMDS) in THF gives the hydroxyester (XI) as a mixture of four diastereomers. This mixture is oxidized with pyridinium chlorochromate (PCC) in dichloromethane to afford the ketoester (XII) also as a mixture of two diastereomers. Elimination of the biphenylyloxymethyl protecting group with H2SO4 in methanol yields the hydroxy ketoester (XIII).
| 【1】 Fors, K.S.; et al.; A convergent, scalable synthesis of HIV protease inhibitor PNU-140690. J Org Chem 1998, 63, 21, 7348. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 | |
| (I) | 17233 | 1-phenyl-3-hexanone | C12H16O | 详情 | 详情 | |
| (II) | 21156 | ethyl 3-hydroxy-3-phenethylhexanoate | C16H24O3 | 详情 | 详情 | |
| (III) | 21157 | 3-hydroxy-3-phenethylhexanoic acid | C14H20O3 | 详情 | 详情 | |
| (IV) | 13355 | 2-Amino-1-phenyl-1-propanol; (1S,2R)-(+)-Norephedrine | 37577-28-9 | C9H13NO | 详情 | 详情 |
| (IV) | 21158 | (1R,2S)-2-amino-1-phenyl-1-propanol | C9H13NO | 详情 | 详情 | |
| (V) | 21159 | (3R)-3-hydroxy-3-phenethylhexanoic acid | C14H20O3 | 详情 | 详情 | |
| (VI) | 21160 | [1,1'-biphenyl]-4-yl chloromethyl ether; 4-(chloromethoxy)-1,1'-biphenyl | C13H11ClO | 详情 | 详情 | |
| (VII) | 21161 | ([1,1'-biphenyl]-4-yloxy)methyl (3R)-3-[([1,1'-biphenyl]-4-yloxy)methoxy]-3-phenethylhexanoate | C40H40O5 | 详情 | 详情 | |
| (VIII) | 21162 | (3R)-3-[([1,1'-biphenyl]-4-yloxy)methoxy]-3-phenethyl-1-hexanol | C27H32O3 | 详情 | 详情 | |
| (IX) | 21163 | (3R)-3-[([1,1'-biphenyl]-4-yloxy)methoxy]-3-phenethylhexanal | C27H30O3 | 详情 | 详情 | |
| (X) | 21164 | methyl (3S)-3-(3-nitrophenyl)pentanoate | C12H15NO4 | 详情 | 详情 | |
| (XI) | 21165 | methyl (5R)-5-[([1,1'-biphenyl]-4-yloxy)methoxy]-3-hydroxy-2-[(1S)-1-(3-nitrophenyl)propyl]-5-phenethyloctanoate | C39H45NO7 | 详情 | 详情 | |
| (XII) | 21166 | methyl (5R)-5-[([1,1'-biphenyl]-4-yloxy)methoxy]-2-[(1S)-1-(3-nitrophenyl)propyl]-3-oxo-5-phenethyloctanoate | C39H43NO7 | 详情 | 详情 | |
| (XIII) | 21167 | methyl (5R)-5-hydroxy-2-[(1S)-1-(3-nitrophenyl)propyl]-3-oxo-5-phenethyloctanoate | C26H33NO6 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(II)The condensation of 2-[6-(dimethylamino)pyridin-3-yl]acetonitrile (I) with ethyl acetate (II) by means of NaH in THF gives 2-[6-(dimethylamino)pyridin-3-yl]-3-oxobutyronitrile (III), which is treated with hydrazine in refluxing ethanol/water to yield the corresponding hydrazone (IV). The cyclization of (IV) with ethyl acetoacetate (V) in refluxing dioxane affords 3-[6-(dimethylamino)pyridin-3-yl]-2,5-dimethylpyrazolo[2,3-a]pyrimidin-7-ol (VI), which is treated with refluxing POCl3 to provide the expected 7-chloro derivative (VII). Finally, this compound is treated with dipropylamine (VIII) in refluxing acetonitrile to furnish the target dipropylamino derivative.
| 【1】 Chen, C.; Webb, T.R.; McCarthy, J.R.; Moran, T.J.; Wilcoxen, K.M. (Janssen Pharmaceutica NV; Neurocrine Biosciences Inc.); Pyrazolopyrimidines as CRF receptor antagonists. EP 0880523; JP 2000503661; WO 9729109 . |
| 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) | 53973 | 2-[6-(dimethylamino)-3-pyridinyl]acetonitrile | n/a | C9H11N3 | 详情 | 详情 |
| (II) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (III) | 53974 | 2-[6-(dimethylamino)-3-pyridinyl]-3-oxobutanenitrile | n/a | C11H13N3O | 详情 | 详情 |
| (IV) | 53975 | 2-[6-(dimethylamino)-3-pyridinyl]-3-[(Z)hydrazono]butanenitrile | n/a | C11H15N5 | 详情 | 详情 |
| (V) | 11819 | ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate | 141-97-9 | C6H10O3 | 详情 | 详情 |
| (VI) | 53976 | 3-[6-(dimethylamino)-3-pyridinyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol | n/a | C15H17N5O | 详情 | 详情 |
| (VII) | 53977 | N-[5-(7-chloro-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-2-pyridinyl]-N,N-dimethylamine; 5-(7-chloro-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-dimethyl-2-pyridinamine | n/a | C15H16ClN5 | 详情 | 详情 |
| (VIII) | 21856 | N,N-dipropylamine; N-propyl-1-propanamine | 142-84-7 | C6H15N | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(II)The condensation of 2-(2,6-dichlorophenyl)acetonitrile (I) with ethyl acetate (II) by means of sodium ethoxide in refluxing ethanol gives 2-(2,6-dichlorophenyl)-3-oxobutyronitrile (III), which is methylated with diazomethane in ether yielding the enol ether (IV). Finally, this compound is cyclized with guanidine (V) by means of sodium ethoxide in refluxing ethanol.
| 【1】 Miller, A.A.; Nobbs, M.S.; Hyde, R.M.; Leach, M.J. (Glaxo Wellcome plc); Pharmacologically active CNS cpds.. AU 8945964; EP 0372934; EP 0713703; EP 0715851; EP 0727212; EP 0727213; EP 0727214; JP 1990202876; US 5587380; US 5597828; US 5635507; US 5684005 . |
| 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) | 18202 | 2-(2,6-dichlorophenyl)acetonitrile; 2,6-Dichlorophenylacetonitrile | 3215-64-3 | C8H5Cl2N | 详情 | 详情 |
| (II) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (III) | 28609 | 2-(2,6-dichlorophenyl)-3-oxobutanenitrile | C10H7Cl2NO | 详情 | 详情 | |
| (IV) | 28610 | (Z)-2-(2,6-dichlorophenyl)-3-methoxy-2-butenenitrile | C11H9Cl2NO | 详情 | 详情 | |
| (V) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：Addition of phenylmagnesium bromide to 6-methoxy-1-indanone (I) gave carbinol (II), which was dehydrated to phenylindene (III) upon treatment with p-toluenesulfonic acid in refluxing toluene. Oxidative cleavage of (III) with Jones reagent in the presence of OsO4 provided 2-benzoyl-4-methoxyphenylacetic acid (IV), which was further reduced to the 2-benzyl analogue (V) by hydrogenation over Pd/C. After conversion of (V) to the corresponding acid chloride (VI) using oxalyl chloride and a trace of DMF, Friedel-Crafts cyclization with AlCl3 furnished the dibenzocycloheptenone (VII). Addition of the lithium enolate of ethyl acetate to the carbonyl group of (VII) in the presence of tetramethylethylenediamine at -78 C generated the hydroxyester (VIII). Then, hydrogenolysis of the benzylic alcohol of (VIII) in the presence of Pd/C gave (IX). Subsequent cleavage of the methyl ether of (IX) by means of ethane thiol and AlCl3 provided the corresponding racemic phenol. Isolation of the required (S)-enantiomer (X) was carried out by chiral HPLC.
| 【1】 Drake, F.H. (SmithKline Beecham plc); Method for stimulating bone formation. EP 0946180; WO 9815278 . |
| 【2】 Miller, W.H.; Samanen, J.M.; Heerding, D.; Bondinell, W.E. (SmithKline Beecham Corp.); Vitronectin receptor antagonists. EP 1025090; WO 9915508 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 | |
| 17616 | bromo(phenyl)magnesium; Phenyl Magnesium Bromide | 100-58-3 | C6H5BrMg | 详情 | 详情 | |
| (I) | 34514 | 6-methoxy-1-indanone | 13623-25-1 | C10H10O2 | 详情 | 详情 |
| (II) | 34515 | 6-methoxy-1-phenyl-1-indanol | C16H16O2 | 详情 | 详情 | |
| (III) | 34516 | 5-methoxy-3-phenyl-1H-indene; methyl 3-phenyl-1H-inden-5-yl ether | C16H14O | 详情 | 详情 | |
| (IV) | 34517 | 2-(2-benzoyl-4-methoxyphenyl)acetic acid | C16H14O4 | 详情 | 详情 | |
| (V) | 34518 | 2-(2-benzyl-4-methoxyphenyl)acetic acid | C16H16O3 | 详情 | 详情 | |
| (VI) | 34519 | 2-(2-benzyl-4-methoxyphenyl)acetyl chloride | C16H15ClO2 | 详情 | 详情 | |
| (VII) | 34520 | 3-methoxy-5,11-dihydro-10H-dibenzo[a,d]cyclohepten-10-one | C16H14O2 | 详情 | 详情 | |
| (VIII) | 34521 | ethyl 2-(10-hydroxy-3-methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl)acetate | C20H22O4 | 详情 | 详情 | |
| (IX) | 34522 | ethyl 2-(3-methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl)acetate | C20H22O3 | 详情 | 详情 | |
| (X) | 34523 | ethyl 2-[(10S)-3-hydroxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-yl]acetate | C19H20O3 | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(III)The reaction of 2,6-dichloro-4-methoxybenzyl chloride (I) with tetraethylammonium cyanide in refluxing dichloromethane gives 2-(2,6-dichloro-4-methoxyphenyl)acetonitrile (II), which is condensed with ethyl acetate (III) by means of sodium ethoxide in refluxing ethanol to yield the 3-oxobutyronitrile (IV). The cyclization of (IV) with hydrazine (V) by means of HOAc in refluxing benzene affords the aminopyrazole (VI), which is further cyclized with ethyl acetoacetate (VII) in refluxing acetic acid to provide 3-(2,6-dichloro-4-methoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol (VIII). The reaction of (VIII) with refluxing POCl3 furnishes the corresponding chloro derivative (IX), which is allowed to react with ethylenediamine (X) in hot acetonitrile to give 7-(2-aminoethylamino)-3-(2,6-dichloro-4-methoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine (XI). Finally, this compound is reductocondensed with tetrahydropyran-4-one (XII) by means of sodium cyanoborohydride in methanol/HOAc to yield the target CP-671906-01.
| 【1】 Giangiordano, M.; Tran, J.; Darrow, J.W.; De Lombaert, S.; Blum, C.; Griffith, D.A.; Carpino, P.A. (Neurogen Corp.; Pfizer Inc.); Certain alkylene diamine-substd. pyrazolo[1,5-a]-1,5-pyrimidines and pyrazolo[1,5-a]-1,3,5-triazines. US 6372743; WO 0123387 . |
| 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) | 52615 | 3,5-dichloro-4-(chloromethyl)phenyl methyl ether; 1,3-dichloro-2-(chloromethyl)-5-(methyloxy)benzene | C8H7Cl3O | 详情 | 详情 | |
| (II) | 52616 | 2-[2,6-dichloro-4-(methyloxy)phenyl]acetonitrile | C9H7Cl2NO | 详情 | 详情 | |
| (III) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (IV) | 52621 | 2-[2,6-dichloro-4-(methyloxy)phenyl]-3-oxobutanenitrile | C11H9Cl2NO2 | 详情 | 详情 | |
| (V) | 27344 | hydrazine | 302-01-2 | H4N2 | 详情 | 详情 |
| (VI) | 52617 | 4-[2,6-dichloro-4-(methyloxy)phenyl]-3-methyl-1H-pyrazol-5-amine; 4-[2,6-dichloro-4-(methyloxy)phenyl]-3-methyl-1H-pyrazol-5-ylamine | C11H11Cl2N3O | 详情 | 详情 | |
| (VII) | 11819 | ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate | 141-97-9 | C6H10O3 | 详情 | 详情 |
| (VIII) | 52618 | 3-[2,6-dichloro-4-(methyloxy)phenyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-ol | C15H13Cl2N3O2 | 详情 | 详情 | |
| (IX) | 52619 | 7-chloro-3-[2,6-dichloro-4-(methyloxy)phenyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidine; 3,5-dichloro-4-(7-chloro-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)phenyl methyl ether | C15H12Cl3N3O | 详情 | 详情 | |
| (X) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (XI) | 52620 | N~1~-{3-[2,6-dichloro-4-(methyloxy)phenyl]-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl}-1,2-ethanediamine | C17H19Cl2N5O | 详情 | 详情 | |
| (XII) | 31563 | tetrahydro-4H-pyran-4-one | 29943-42-8 | C5H8O2 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(IV)The chiral intermediate (X) is prepared by two methods. Treatment of lactonitrile (I) with HCl/EtOH affords imidate (II), which is further reacted with ethanolic ammonia to produce amidine (III). Claisen condensation between ethyl acetate (IV) and ethyl formate (V) in the presence of NaH provides the sodium salt of ethyl 3-hydroxyacrylate (VI). Cyclization of (VI) with amidine (III) then furnishes the racemic pyrimidinone (VII). Kinetic resolution of (VII) is accomplished by acylation with vinyl butyrate (VIII) in the presence of lipase P30 to yield a mixture of unreacted (S)-alcohol (IX) and the desired (R)-butyrate ester (X), which can be separated by partition between CH2Cl2 and H2O.
| 【1】 Mylari, B.L.; Zembrowski, W.J.; Murry, J.A.; Chu-Moyer, M.Y. (Pfizer Products Inc.); Aminopyrimidines as sorbitol dehydrogenase inhibitors. EP 1185275; US 6414149; WO 0059510 . |
| 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) | 64060 | 2-hydroxypropanenitrile | C3H5NO | 详情 | 详情 | |
| (II) | 64061 | ethyl 2-hydroxypropanimidoate | C5H11NO2 | 详情 | 详情 | |
| (III) | 64062 | 2-hydroxypropanimidamide | C3H8N2O | 详情 | 详情 | |
| (IV) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (V) | 16602 | ethyl formate | 109-94-4 | C3H6O2 | 详情 | 详情 |
| (VI) | 64063 | sodium (E)-3-ethoxy-3-oxo-1-propen-1-olate | C5H7NaO3 | 详情 | 详情 | |
| (VII) | 64064 | 2-(1-hydroxyethyl)-4(3H)-pyrimidinone | C6H8N2O2 | 详情 | 详情 | |
| (VIII) | 53263 | n-Butyric acid vinyl ester; Vinyl n-butyrate; Vinyl butyrate | 123-20-6 | C6H10O2 | 详情 | 详情 |
| (IX) | 64065 | 2-[(1S)-1-hydroxyethyl]-4(3H)-pyrimidinone | C6H8N2O2 | 详情 | 详情 | |
| (X) | 64066 | (1R)-1-(6-oxo-1,6-dihydro-2-pyrimidinyl)ethyl butyrate | C10H14N2O3 | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(XIII)Condensation of 1-tritylimidazole-4-carbaldehyde (IV) with ethyl acetate (XIII) using LDA in THF furnishes ethyl 3-hydroxy-3-(1-trityl-4-imidazolyl)propanoate (XIV), which by reduction with LiAlH4 in THF affords diol (XV). Selective oxidation of the secondary alcohol of compound (XV) by means of MnO2 in CH2Cl2 gives 3-hydroxy-1-(1-trityl-4-imidazolyl)-1-propanone (XVI), which upon hydroxyl group activation with MsCl and Et3N in EtOAc followed by cyclization in the presence of Et3N and MeOH in acetonitrile at 70 °C yields 5,6-dihydro-7H-pyrrolo[1,2-c]imidazol-7-one (XVII). Coupling of ketone (XVII) with metalated 6-bromo-N-methyl-2-naphthamide (XVIII) [prepared by amidation of 6-bromo-2-naphthoic acid (I) with CH3NH2 by means of EDC, HOBt and DIEA in DMF] with BuLi and optionally 2-bromobenzotrifluoride in THF provides the 7-(2-naphthyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-ol derivative (XIX), which is finally resolved by crystallization with (2S,3S)-(–)-tartranilic acid followed by addition of NaOH or by chiral HPLC separation .
Intermediate (XVI) can alternatively be prepared by addition of HBr to 1-(1-trityl-4-imidazolyl)-2-propen-1-one (XX) in AcOH to afford the bromoketone (XXI) and then cyclization in the presence of Et3N .
| 【1】 Hitaka, T., Kusaka, M., Aoki, I., Ojida, A., Matsunaga, N., Adachi, M., Tasaka, A. (Takeda Pharmaceutical Co., Ltd.). Novel imidazole derivatives, production method thereof and use thereof. EP 1334106, EP 1681290, JP 2003201282, JP 2006045239, US 7141598, WO 2002040484. |
| 【2】 Kaku, T., Hitaka, T., Ojida, A. et al. Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorg Med Chem 2011, 19(21): 6383-99. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 27712 | 1-trityl-1H-imidazole-4-carbaldehyde；1-Tritylimidazole-4-carboxaldehyde | 33016-47-6 | C23H18N2O | 详情 | 详情 |
| (XIII) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (XIV) | 68266 | ethyl 3-hydroxy-3-(1-trityl-4-imidazolyl)propanoate | C27H26N2O3 | 详情 | 详情 | |
| (XV) | 68267 | 1-(1-trityl-1H-imidazol-4-yl)propane-1,3-diol | C25H24N2O2 | 详情 | 详情 | |
| (XVI) | 68268 | 3-hydroxy-1-(1-trityl-1H-imidazol-4-yl)propan-1-one;3-hydroxy-1-(1-trityl-4-imidazolyl)-1-propanone | C25H22N2O2 | 详情 | 详情 | |
| (XVII) | 68269 | 5,6-dihydro-7H-pyrrolo[1,2-c]imidazol-7-one;5H-pyrrolo[1,2-c]imidazol-7(6H)-one | C6H6N2O | 详情 | 详情 | |
| (XVIII) | 68270 | 6-bromo-N-methyl-2-naphthamide | C12H10BrNO | 详情 | 详情 | |
| (XIX) | 68271 | 7-(2-naphthyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-ol;6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide | C18H17N3O2 | 详情 | 详情 | |
| (XX) | 68272 | 1-(1-trityl-4-imidazolyl)-2-propen-1-one;1-(1-trityl-1H-imidazol-4-yl)prop-2-en-1-one | C25H20N2O | 详情 | 详情 | |
| (XXI) | 68273 | 3-bromo-1-(1H-imidazol-4-yl)propan-1-one | C6H7BrN2O | 详情 | 详情 |
合成路线13
该中间体在本合成路线中的序号：(XIII)Alternatively, racemate (XIX) is obtained by aldol condensation of ketone (VI) with ethyl acetate (XIII) by means of LDA to yield the racemic β-hydroxy ester (XXII), which by reduction with Red-Al in toluene furnishes the corresponding diol (XXIII). Activation of diol (XXIII) with MsCl in the presence of DIEA in THF followed by cyclization by means of DIEA and MeOH in acetonitrile gives the 7-(2-naphthyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-ol derivative (XXIV). Finally, the N,N-diisopropyl-2-naphthamide derivative (XXVI) is treated with CH3NH2 in the presence of BuLi in THF .
| 【1】 Kaku, T., Hitaka, T., Ojida, A. et al. Discovery of TAK-700, a naphthylmethylimidazole derivative, as a highly selective, orally active 17, 20 lyase inhibitor for prostate cancer. 240th ACS Natl Meet (Aug 22-26, Boston) 2010, Abst MEDI 96. |
| 【2】 Hitaka, T., Kusaka, M., Aoki, I., Ojida, A., Matsunaga, N., Adachi, M., Tasaka, A. (Takeda Pharmaceutical Co., Ltd.). Novel imidazole derivatives, production method thereof and use thereof. EP 1334106, EP 1681290, JP 2003201282, JP 2006045239, US 7141598, WO 2002040484. |
| 【3】 Kaku, T., Hitaka, T., Ojida, A. et al. Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorg Med Chem 2011, 19(21): 6383-99. |
| 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) | 68258 | N,N-diisopropyl-6-(1-trityl-1H-imidazole-4-carbonyl)-2-naphthamide | C40H37N3O2 | 详情 | 详情 | |
| (XIII) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (XIX) | 68271 | 7-(2-naphthyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-ol;6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide | C18H17N3O2 | 详情 | 详情 | |
| (XXII) | 68274 | racemic ethyl 3-(6-(diisopropylcarbamoyl)naphthalen-2-yl)-3-hydroxy-3-(1-trityl-1H-imidazol-4-yl)propanoate | C44H45N3O4 | 详情 | 详情 | |
| (XXIII) | 68275 | 6-(1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl)-N,N-diisopropyl-2-naphthamide (XXIV) C23H27N3O2 7-(2-naphthyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-ol | C42H43N3O3 | 详情 | 详情 | |
| (XXIV) | 68276 | 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N,N-diisopropyl-2-naphthamide | C23H27N3O2 | 详情 | 详情 |
合成路线14
该中间体在本合成路线中的序号：(XXVIII)The chiral precursor (X) has been obtained from pyridine (V) by two different strategies. Heck coupling of 2,6-diethyl-4-bromopyridine (V) with benzyl 3(S)-cyclopentyl-3-hydroxy-4-pentenoate (XXIV) in the presence of Pd(OAc)2, Bu4NCl and (c-Hex)2NMe in DMA at 90 °C affords benzyl 3-cyclopentyl-5-(2,6-diethylpyridin-4-yl)-3(R)-hydroxypent-4-enoate (XXV), which finally undergoes double bond reduction and O-debenzylation by means of H2 over Pd/C in EtOH .
Alternatively, coupling of 4-bromo-2,6-diethylpyridine (V) with 1-cyclopentyl-2-propen-1-ol (XXVI) in the presence of Pd(OAc)2, LiBr and Et3N in DMA/H2O gives rise to 1-cyclopentyl-3-(2,6-diethyl-4-pyridinyl)-1-propanone (XXVII). Subsequent condensation of ketone (XXVII) with ethyl acetate (XXVIII) by means of LiHMDS in THF affords the hydroxy ester (XXIX), which by hydrolysis with NaOH in H2O/THF yields the racemic free acid (XXX). Finally, fractional crystallization of carboxylic acid (XXX) with (1R,2R)-2-amino-1-(4-nitrophenyl) propane-1,3-diol in THF provides the desired (R)-enantiomer (X). The undesired (S)-enantiomer (XXXI), obtained from the mother liquors of resolution of compound (XXX), can be recycled by esterification with EtOH and H2SO4 in refluxing THF, followed by retroaldol reaction of the obtained hydroxy ester in the presence of t-BuOK in MTBE to produce ketone (XXVII) .
| 【1】 Johnson, S., Drowns, M., Tatlock, J. et al. Synthetic route optimization of PF-00868554, an HCV polymerase inhibitor in clinical evaluation. Synlett 2010(5): 796-800. |
| 【2】 Matthews, C.F., Scott, R.W., Tucker, J.L. (Pfizer, Inc.). CN 102336758, EP 1928878, JP 2007056022, US 2009023921, US 7807838, WO 2007023381. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 68333 | 4-bromo-2,6-diethylpyridine | 877133-54-5 | C9H12BrN | 详情 | 详情 |
| (X) | 68339 | (R)-3-cyclopentyl-5-(2,6-diethylpyridin-4-yl)-3-hydroxypentanoic acid | C19H29NO3 | 详情 | 详情 | |
| (XXIV) | 68348 | (S)-benzyl 3-cyclopentyl-3-hydroxypent-4-enoate;benzyl 3(S)-cyclopentyl-3-hydroxy-4-pentenoate | C17H22O3 | 详情 | 详情 | |
| (XXV) | 68349 | 3-cyclopentyl-5-(2,6-diethylpyridin-4-yl)-3(R)-hydroxypent-4-enoate;(R,E)-benzyl 3-cyclopentyl-5-(2,6-diethylpyridin-4-yl)-3-hydroxypent-4-enoate | C26H33NO3 | 详情 | 详情 | |
| (XXVI) | 68350 | 1-cyclopentylprop-2-en-1-ol | C8H14O | 详情 | 详情 | |
| (XXVII) | 68351 | 1-cyclopentyl-3-(2,6-diethyl-4-pyridinyl)-1-propanone | C17H25NO | 详情 | 详情 | |
| (XXVIII) | 17491 | ethyl acetate | 141-78-6 | C4H8O2 | 详情 | 详情 |
| (XXIX) | 68352 | ethyl 3-cyclopentyl-5-(2,6-diethylpyridin-4-yl)-3-hydroxypentanoate | C21H33NO3 | 详情 | 详情 | |
| (XXX) | 68353 | racemic 3-cyclopentyl-5-(2,6-diethylpyridin-4-yl)-3-hydroxypentanoic acid | C19H29NO3 | 详情 | 详情 | |
| (XXXI) | 68354 | (S)-3-cyclopentyl-5-(2,6-diethylpyridin-4-yl)-3-hydroxypentanoic | C19H29NO3 | 详情 | 详情 |