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【结 构 式】 
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【分子编号】61128 【品名】 【CA登记号】 |
【 分 子 式 】C4H8 【 分 子 量 】56.10752 【元素组成】C 85.63% H 14.37% |
合成路线1
该中间体在本合成路线中的序号：(III)In an alternative synthesis, which does not utilize the alkaloid catharanthine, Sharpless asymmetric epoxidation of 2-ethyl-2-propenol (I) in the presence of ( )-diethyl tartrate provides (R)-2-ethyl-2,3-epoxypropanol (II). Subsequent addition of allylmagnesium chloride (III) to epoxide (II) leads to diol (IV), which is further protected as the corresponding acetonide (V) with 2,2 dimethoxypropane and p-TsOH. Ozonolysis of the terminal olefin (V) gives rise to aldehyde (VI). Condensation of aldehyde (VI) with the indoloazapine (VII) furnishes the bridged azepine (VIII) as a diastereomeric mixture. Without isolation, this mixture of amines is N-alkylated with benzyl bromide, and the resultant ammonium salts (IX) are subjected to rearrangement in boiling MeOH in the presence of Et3N to provide an equimolecular mixture of the tetracyclic diastereoisomers (X) and (XI) (5).
| 【1】 Kuehne, M.E.; Matson, P.A..; Bornmann, W.G.; Enantioselective syntheses of vinblastine, leurosidine, vincovaline, and 20'-epi-vincovaline. J Org Chem 1991, 56, 2, 513. |
| 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) | 63603 | 2-ethyl-2-propen-1-ol | C5H10O | 详情 | 详情 | |
| (II) | 63604 | (2-ethyl-2-oxiranyl)methanol | C5H10O2 | 详情 | 详情 | |
| (III) | 61128 | C4H8 | 详情 | 详情 | ||
| (IV) | 63605 | 2-ethyl-5-hexene-1,2-diol | C8H16O2 | 详情 | 详情 | |
| (V) | 63606 | 4-(3-butenyl)-4-ethyl-2,2-dimethyl-1,3-dioxolane | C11H20O2 | 详情 | 详情 | |
| (VI) | 63607 | 3-(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)propanal | C10H18O3 | 详情 | 详情 | |
| (VII) | 63608 | methyl 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate | C14H16N2O2 | 详情 | 详情 | |
| (VIII) | 63609 | methyl 15-{2-[(4S)-4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl}-8,12-diazatetracyclo[10.2.1.0~1,9~.0~2,7~]pentadeca-2,4,6,9-tetraene-10-carboxylate | C24H32N2O4 | 详情 | 详情 | |
| (IX) | 63610 | 12-benzyl-15-{2-[(4S)-4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl}-10-(methoxycarbonyl)-8-aza-12-azoniatetracyclo[10.2.1.0~1,9~.0~2,7~]pentadeca-2,4,6,9-tetraene bromide | C31H39BrN2O4 | 详情 | 详情 | |
| (X) | 63611 | methyl 4-[(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O4 | 详情 | 详情 | |
| (XI) | 63612 | methyl 4-[(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate | C31H38N2O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)The reaction of 1(R)-phenylethane-1,2-diol (I) with N-hydroxyphthalimide (II) by means of DEAD and PPh3 gives the N-alcoxyphthalimide (III) with(S)-configuration. The hydrazinolysis of (III) with hydrazine hydrate affords the O-alkylhydroxylamine (IV), which is condensed with benzaldehyde (V) to provide the alkylated benzaldoxime (VI). The alkylation of the oxime (VI) with vinyl lithium (VII) in toluene gives the N, O dialkylated hydroxylamine (VIII), which is treated with Zn and AcOH to yield 1(R)-phenylallylamine (IX). The protection of the amine (IX) with Boc2O and NaOH affords the carbamate (X), which is oxidized at the vinyl double bond by means of OsO4 and NaIO4 to provide the acetaldehyde (XI). The reaction of aldehyde (XI) with allylmagnesium bromide (XII) in ethyl ether gives the aminoalcohol (XIII), which is protected with Tbdms-Cl and imidazole to yield the silyl ether (XIV).
| 【1】 Yamazaki, N.; et al.; Nucleophilic addition of methyllithium to chiral oxime ethers: Asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue. Tetrahedron Lett 2001, 42, 30, 5029. |
| 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) | 56141 | (R)-(-)-1-Phenyl-1,2-ethanediol; (R)-(-)-alpha,beta-Dihydroxyethylbenzene; (R)-(-)-Phenyl-1,2-ethanediol; (R)-(-)-Styrene glycol; (-)-Styrene glycol | 16355-00-3 | C8H10O2 | 详情 | 详情 |
| (II) | 13505 | N-Hydroxyphthalimide; 2-Hydroxy-1H-isoindole-1,3(2H)-dione | 524-38-9 | C8H5NO3 | 详情 | 详情 |
| (III) | 56142 | 2-{[(1S)-2-hydroxy-1-phenylethyl]oxy}-1H-isoindole-1,3(2H)-dione | C16H13NO4 | 详情 | 详情 | |
| (IV) | 56143 | (2S)-2-(aminooxy)-2-phenyl-1-ethanol | C8H11NO2 | 详情 | 详情 | |
| (V) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (VI) | 62256 | benzaldehyde O-[(1S)-2-hydroxy-1-phenylethyl]oxime | C15H15NO2 | 详情 | 详情 | |
| (VII) | 42368 | vinyllithium | 917-57-7 | C2H3Li | 详情 | 详情 |
| (VIII) | 62257 | (2S)-2-phenyl-2-({[(1R)-1-phenyl-2-propenyl]amino}oxy)-1-ethanol | C17H19NO2 | 详情 | 详情 | |
| (IX) | 62258 | (1R)-1-phenyl-2-propenylamine; (1R)-1-phenyl-2-propen-1-amine | C9H11N | 详情 | 详情 | |
| (X) | 62259 | tert-butyl (1R)-1-phenyl-2-propenylcarbamate | C14H19NO2 | 详情 | 详情 | |
| (XI) | 45428 | tert-butyl (1S)-2-oxo-1-phenylethylcarbamate | C13H17NO3 | 详情 | 详情 | |
| (XII) | 61128 | C4H8 | 详情 | 详情 | ||
| (XIII) | 62260 | tert-butyl (1S)-2-hydroxy-1-phenyl-4-pentenylcarbamate | C16H23NO3 | 详情 | 详情 | |
| (XIV) | 62261 | tert-butyl (1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-1-phenyl-4-pentenylcarbamate | C22H37NO3Si | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VI)The reaction of benzyl-alpha-D-mannoside (I) with Ts-Cl in pyridine gives the 6-O-tosylate (II), which is treated with 2,2-dimethoxypropane (III), trimethyl orthoacetate and naphthalenesulfonic acid to yield the acetonide (IV). The silylation of the remaining OH group of (IV) with Tms-Cl and TEA in THF affords the silyl ether (V), which is condensed with allylmagnesium bromide (VI) in ethyl ether to provide the olefinic compound (VII). The desilylation of (VII) by means of TBAF in THF gives the secondary alcohol (VIII); which is oxidized by means of (COCl)2, DMSO and TEA in dichloromethane to yield the ketone derivative (IX). The oxidation of the terminal double bond of (IX) by means of RuO2 and NaIO4 in CCl4/acetonitrile affords the carboxylic acid (X), which is methylated with diazomethane to provide the corresponding methyl ester (XI). Alternatively the propionic ester (XI) can also be obtained by the following sequence: The condensation of the silyl ether (V) with the sodium salt of diethyl malonate (XII) in refluxing toluene gives the malonyl derivative (XIII), which is treated with NaCl at 145 C, yielding the lactone (XIV). The methanolysis of (XIV) with KOH in methanol affords the hydroxyester (XV), which is finally oxidized with PCC in dichloromethane to provide the target ketoester (XI), already reported. The reduction of the carbonyl group of (XI) by means of NaBH4 in ethanol gives the hydroxyester (XVI), which is treated with triflic anhydride and pyridine to yield the corresponding triflate (XVII). The reaction of (XVII) with sodium azide in DMF affords the azido derivative (XVIII), which is reduced with H2 over Pd/C to provide the expected amino derivative (XIX). The cyclization of (XIX) in refluxing toluene gives the lactam (XX), which is finally reduced to the target perhydro-pyrano[3,2-b]pyridine (XXI) intermediate.
| 【1】 Bermejo Gonzalez, F.; et al.; Efficient preparation of a valuable intermediate in the synthesis of (-)-swainsonine. Bull Chem Soc Jpn 1992, 65, 2, 567. |
| 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) | 62617 | (2S,3S,4S,5S,6R)-2-(benzyloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol | C13H18O6 | 详情 | 详情 | |
| (II) | 62659 | [(2R,3S,4S,5S,6S)-6-(benzyloxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl]methyl 4-methylbenzenesulfonate | C20H24O8S | 详情 | 详情 | |
| (III) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (IV) | 62660 | [(3aS,4S,6R,7R,7aS)-4-(benzyloxy)-7-hydroxy-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl]methyl 4-methylbenzenesulfonate | C23H28O8S | 详情 | 详情 | |
| (V) | 62661 | {(3aS,4S,6R,7R,7aR)-4-(benzyloxy)-2,2-dimethyl-7-[(trimethylsilyl)oxy]tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl}methyl 4-methylbenzenesulfonate | C26H36O8SSi | 详情 | 详情 | |
| (VI) | 61128 | C4H8 | 详情 | 详情 | ||
| (VII) | 62662 | (3aS,4S,6R,7R,7aR)-4-(benzyloxy)-6-(3-butenyl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-yl trimethylsilyl ether; {[(3aS,4S,6R,7R,7aR)-4-(benzyloxy)-6-(3-butenyl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-yl]oxy}(trimethyl)silane | C22H34O5Si | 详情 | 详情 | |
| (VIII) | 62663 | (3aS,4S,6R,7R,7aS)-4-(benzyloxy)-6-(3-butenyl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-7-ol | C19H26O5 | 详情 | 详情 | |
| (IX) | 62664 | (3aS,4S,6R,7aR)-4-(benzyloxy)-6-(3-butenyl)-2,2-dimethyldihydro-4H-[1,3]dioxolo[4,5-c]pyran-7(6H)-one | C19H24O5 | 详情 | 详情 | |
| (X) | 62665 | 3-[(3aS,4S,6R,7aR)-4-(benzyloxy)-2,2-dimethyl-7-oxotetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl]propanoic acid | C18H22O7 | 详情 | 详情 | |
| (XI) | 62667 | methyl 3-[(3aS,4S,6R,7aR)-4-(benzyloxy)-2,2-dimethyl-7-oxotetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl]propanoate | C19H24O7 | 详情 | 详情 | |
| (XII) | 16336 | [2-ethoxy-1-(ethoxycarbonyl)-2-oxoethyl]sodium | C7H11NaO4 | 详情 | 详情 | |
| (XIII) | 62666 | diethyl 2-({(3aS,4S,6R,7R,7aR)-4-(benzyloxy)-2,2-dimethyl-7-[(trimethylsilyl)oxy]tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl}methyl)malonate | C26H40O9Si | 详情 | 详情 | |
| (XIV) | 62669 | (3aS,4S,5aR,9aR,9bR)-4-(benzyloxy)-2,2-dimethylhexahydro[1,3]dioxolo[4,5-d]pyrano[3,2-b]pyran-8(4H)-one | C18H22O6 | 详情 | 详情 | |
| (XV) | 62668 | methyl 3-[(3aS,4S,6R,7R,7aS)-4-(benzyloxy)-7-hydroxy-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl]propanoate | C19H26O7 | 详情 | 详情 | |
| (XVI) | 62670 | methyl 3-[(3aS,4S,6R,7S,7aS)-4-(benzyloxy)-7-hydroxy-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl]propanoate | C19H26O7 | 详情 | 详情 | |
| (XVII) | 62671 | methyl 3-((3aS,4S,6R,7S,7aR)-4-(benzyloxy)-2,2-dimethyl-7-{[(trifluoromethyl)sulfonyl]oxy}tetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl)propanoate | C20H25F3O9S | 详情 | 详情 | |
| (XVIII) | 62672 | methyl 3-[(3aS,4S,6R,7R,7aS)-7-azido-4-(benzyloxy)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl]propanoate | C19H25N3O6 | 详情 | 详情 | |
| (XIX) | 62673 | methyl 3-[(3aS,4S,6R,7R,7aS)-7-amino-4-(benzyloxy)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-6-yl]propanoate | C19H27NO6 | 详情 | 详情 | |
| (XX) | 62674 | (3aS,4S,5aR,9aR,9bS)-4-(benzyloxy)-2,2-dimethylhexahydro-4H-[1,3]dioxolo[4',5':4,5]pyrano[3,2-b]pyridin-8(5aH)-one | C18H23NO5 | 详情 | 详情 | |
| (XXI) | 62626 | (3aS,4S,5aR,9aR,9bS)-2,2-dimethyloctahydro-4H-[1,3]dioxolo[4',5':4,5]pyrano[3,2-b]pyridin-4-yl benzyl ether; (3aS,4S,5aR,9aR,9bS)-4-(benzyloxy)-2,2-dimethyloctahydro-4H-[1,3]dioxolo[4',5':4,5]pyrano[3,2-b]pyridine | C18H25NO4 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(IV)The synthesis of the dihydropyranyl acetaldehyde intermediate (XVII) has been obtained as follows: The reduction of the pentanedioic acid monoethyl ester (I) with BH3 gives the hydroxyester (II), which is oxidized with DMP to yield the aldehyde (III). The reaction of (III) with the chiral borane (IV) affords the 5-hydroxyoctenoic ester (V), which is treated with dimethylamine to provide the corresponding amide (VI). The reaction of (VI) with propenal diethylacetal (VII) gives ether (VIII), which is submitted to a ring closing metathesis reaction catalyzed by a Ru catalyst to yield the dihydropyran derivative (IX). The reaction of (IX) with tert-butyldimethylsilyloxy ethylene (X) catalyzed by LiClO4 affords the dihydropyranyl acetaldehyde (XI), which is reduced with NaBH4 and protected with Tes-Cl to provide the butyramide (XII). The reaction of (XII) with MeLi gives the pentanone (XIII), which is treated with Ph-NTf2 and KHMDS to yield the enol triflate (XIV). The reaction of (XIV) with Tms-CH2-MgCl affords the methylene derivative (XV), which is selectively desilylated with K2CO3 to provide the dihdyropyranyl ethanol compound (XVI). Finally, this compound is oxidized with DMP to obtain the target dihydropyranyl acetaldehyde intermediate (XVII).
| 【1】 Ahmed, A.; Hoegenauer, E.K.; Enev, V.S.; Hanbauer, M.; Kaehlig, H.; Ohler, E.; Mulzer, J.; Total synthesis of the microtubule stabilizing antitumor agent laulimalide and some nonnatural analogues: The power of Sharpless' asymmetric epoxidation. J. Org. Chem. 2003, 68, 8, 3026. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 61304 | Trimethylsilylmethylmagnesium Chloride; (Trimethylsilyl)methylmagnesium chloride Solution; Chloro[(trimethylsilyl)methyl]magnesium; (TRIMETHYLSILYLMETHYL)MAGNESIUM CHLORIDE; (TRIMETHYLSILYL)METHYLMAGNESIUM CHL. SOL | 13170-43-9 | C4H11ClMgSi | 详情 | 详情 |
| (I) | 61124 | (3R)-3-methyl-5-oxo-5-propoxypentanoic acid | C9H16O4 | 详情 | 详情 | |
| (II) | 61125 | propyl (3R)-5-hydroxy-3-methylpentanoate | C9H18O3 | 详情 | 详情 | |
| (III) | 61126 | propyl (3R)-3-methyl-5-oxopentanoate | C9H16O3 | 详情 | 详情 | |
| (IV) | 61128 | C4H8 | 详情 | 详情 | ||
| (V) | 61127 | propyl (3R,5S)-5-hydroxy-3-methyl-7-octenoate | C12H22O3 | 详情 | 详情 | |
| (VI) | 61129 | (3R,5S)-5-hydroxy-N,N,3-trimethyl-7-octenamide | C11H21NO2 | 详情 | 详情 | |
| (VII) | 61131 | 1-propoxy-2-propenyl propyl ether; 3,3-dipropoxy-1-propene | C9H18O2 | 详情 | 详情 | |
| (VIII) | 61130 | (3R,5S)-N,N,3-trimethyl-5-[(1-propoxy-2-propenyl)oxy]-7-octenamide | C17H31NO3 | 详情 | 详情 | |
| (IX) | 61132 | (3R)-N,N,3-trimethyl-4-[(2S)-6-propoxy-3,6-dihydro-2H-pyran-2-yl]butanamide | C15H27NO3 | 详情 | 详情 | |
| (X) | 61133 | tert-butyl(dimethyl)(vinyloxy)silane; tert-butyl(dimethyl)silyl vinyl ether | C8H18OSi | 详情 | 详情 | |
| (XI) | 61134 | (3R)-N,N,3-trimethyl-4-[(2S,6R)-6-(2-oxoethyl)-3,6-dihydro-2H-pyran-2-yl]butanamide | C14H23NO3 | 详情 | 详情 | |
| (XII) | 61135 | (3R)-N,N,3-trimethyl-4-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)butanamide | C20H39NO3Si | 详情 | 详情 | |
| (XIII) | 61136 | (4R)-4-methyl-5-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)-2-pentanone | C19H36O3Si | 详情 | 详情 | |
| (XIV) | 61137 | 1-[(2R)-2-methyl-3-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)propyl]vinyl trifluoromethanesulfonate | C20H35F3O5SSi | 详情 | 详情 | |
| (XV) | 61138 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)ethyl triethylsilyl ether; trimethyl{2-[(2S)-2-methyl-3-((2S,6R)-6-{2-[(triethylsilyl)oxy]ethyl}-3,6-dihydro-2H-pyran-2-yl)propyl]-2-propenyl}silane | C23H46O2Si2 | 详情 | 详情 | |
| (XVI) | 61139 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)-1-ethanol | C17H32O2Si | 详情 | 详情 | |
| (XVII) | 61140 | 2-((2R,6S)-6-{(2S)-2-methyl-4-[(trimethylsilyl)methyl]-4-pentenyl}-5,6-dihydro-2H-pyran-2-yl)acetaldehyde | C17H30O2Si | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(XXVII)The reaction of the chiral diol (XXIV) first with MsCl and TEA, and then with NaCN gives the chiral butyronitrile (XXV), which is reduced with DIBAL in dichloromethane to yield the butyraldehyde (XXVI). The reaction of (XXVI) with allyl tributyl tin (XXVII), (S)-BINOL and Ti(OiPr)4 affords the secondary alcohol (XXVIII), which is condensed with acetal (XXIX) by means of PPTS to provide the diene (XXX). A ring closing metathesis reaction in (XXX) by means of a Ru catalyst gives the dihydropyran derivative (XXXI). Alternatively, the reaction of (XXVIII) with propenoyl chloride (XXXII) by means of TEA gives the diene (XXXIII), which is submitted to a ring closing metathesis reaction as before to yield the dihydropyranone (XXXIV). The reduction of (XXXIV) with DIBAL, followed by treatment with CSA and ethanol affords the dihydropyran derivative (XXXV). The reaction of both acetals (XXXI) or (XXXV) with CH2=CH-O-Tbdms (XXXVI) in the presence of Montmorillonite as Lewis acid, followed by a treatment with NaBH4 provides the dihydropyran (XXXVII) as a single isomer.
| 【1】 Ghosh, A.K.; Wang, Y.; Kim, J.T.; Total synthesis of microtubule-stabilizing agent (-)-laulimalide. J Org Chem 2001, 66, 26, 8973. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIV) | 63122 | (2R)-3-(benzyloxy)-2-methyl-1-propanol | C11H16O2 | 详情 | 详情 | |
| (XXV) | 63123 | (3R)-4-(benzyloxy)-3-methylbutanenitrile | C12H15NO | 详情 | 详情 | |
| (XXVI) | 63124 | (3R)-4-(benzyloxy)-3-methylbutanal | C12H16O2 | 详情 | 详情 | |
| (XXVII) | 61128 | C4H8 | 详情 | 详情 | ||
| (XXVIII) | 63125 | (4S,6R)-7-(benzyloxy)-6-methyl-1-hepten-4-ol | C15H22O2 | 详情 | 详情 | |
| (XXIX) | 63126 | 3,3-diethoxy-1-propene; 1-ethoxy-2-propenyl ethyl ether | C7H14O2 | 详情 | 详情 | |
| (XXX) | 63127 | 1-[({(2R,4S)-4-[(1-ethoxy-2-propenyl)oxy]-2-methyl-6-heptenyl}oxy)methyl]benzene; benzyl (2R,4S)-4-[(1-ethoxy-2-propenyl)oxy]-2-methyl-6-heptenyl ether | C20H30O3 | 详情 | 详情 | |
| (XXXI) | 63128 | (2S,6R)-2-[(2R)-3-(benzyloxy)-2-methylpropyl]-6-ethoxy-3,6-dihydro-2H-pyran; benzyl (2R)-3-[(2S,6R)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether | C18H26O3 | 详情 | 详情 | |
| (XXXII) | 11577 | Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride | 814-68-6 | C3H3ClO | 详情 | 详情 |
| (XXXIII) | 63130 | (1S)-1-[(2R)-3-(benzyloxy)-2-methylpropyl]-3-butenyl acrylate | C18H24O3 | 详情 | 详情 | |
| (XXXIV) | 63131 | (6S)-6-[(2R)-3-(benzyloxy)-2-methylpropyl]-5,6-dihydro-2H-pyran-2-one | C16H20O3 | 详情 | 详情 | |
| (XXXV) | 63132 | (2S,6S)-2-[(2R)-3-(benzyloxy)-2-methylpropyl]-6-ethoxy-3,6-dihydro-2H-pyran; benzyl (2R)-3-[(2S,6S)-6-ethoxy-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether | C18H26O3 | 详情 | 详情 | |
| (XXXVI) | 61133 | tert-butyl(dimethyl)(vinyloxy)silane; tert-butyl(dimethyl)silyl vinyl ether | C8H18OSi | 详情 | 详情 | |
| (XXXVII) | 63129 | benzyl (2R)-3-[(2S,6R)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,6-dihydro-2H-pyran-2-yl]-2-methylpropyl ether; (2-{(2R,6S)-6-[(2R)-3-(benzyloxy)-2-methylpropyl]-5,6-dihydro-2H-pyran-2-yl}ethoxy)(tert-butyl)dimethylsilane | C24H40O3Si | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(II)Palladium-catalyzed coupling between the known vinyl triflate (I) and allyl tributyltin (II) provides adduct (III). Then, reduction of the ester function of (III) by means of DIBAL in cold toluene leads to the target allylic alcohol.
| 【1】 Gibbs, B.S.; et al.; Novel farnesol and geranylgeraniol analogues: A potential new class of anticancer agents directed against protein prenylation. J Med Chem 1999, 42, 19, 3800. |
合成路线7
该中间体在本合成路线中的序号：(XII)Lithiation of 1,3-dimethoxybenzene (I), followed by addition of triisopropyl borate to the resultant lithio derivative (II) provided boronic acid (III). This was subjected to palladium-catalyzed Suzuki coupling with methyl 5-nitro-2-bromobenzoate (IV) to afford the biphenyl compound (V). Cleavage of the methyl ethers of (V) using boron tribromide gave rise to the tricyclic lactone (VI). After methylation of the hydroxyl group of (VI) with iodomethane and cesium carbonate, the resultant nitro derivative (VII) was reduced to amine (VIII) by catalytic hydrogenation. Iodine-catalyzed condensation of amine (VIII) with acetone at 105 ºC in a sealed vessel furnished the benzopyranoquinoline system (IX). The lactone function of (IX) was then reduced to the corresponding lactol (X) by means of DIBAL in cold dichloromethane. Subsequent treatment of (X) with methanol and p-toluenesulfonic acid produced acetal (XI). The acetal methoxy group of (XI) was finally displaced with allyl trimethylsilane (XII) in the presence of boron trifluoride etherate to furnish the title allyl derivative
| 【1】 Halbeisen, S.; Schmitt, R.; Birnbock, H.; Hopfgartner, G.; Van Marle, S.P.; Weber, C.; Single dose pharmacokinetics of bosentan in healthy man. 4th Int Conf Endothelin (April 23 1995, London) 1995, Abst P131. |
| 【2】 Wang, A.X.; Kym, P.R.; Jones, T.K.; Kort, M.E.; Edwards, J.P.; Moore, J.L.; Elmore, S.W.; Coughlan, M.J.; Pratt, J.K. (Abbott Laboratories Inc.; Ligand Pharmaceuticals, Inc.); Glucocorticoid-selective anti-inflammatory agents. EP 1053239; WO 9941256 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 23199 | 2-Propanone; Acetone; beta-ketopropane; chevron acetone;propan-2-one； Dimethyl formaldehyde; Dimethyl ketone; dimethylketal; Ketone propane; Methyl ketone; Propanone; Pyroacetic acid; Pyroacetic ether | 67-64-1 | C3H6O | 详情 | 详情 |
| (I) | 11934 | m-Dimethoxybenzene; 1,3-Dimethoxybenzene; 3-Methoxyphenyl methyl ether | 151-10-0 | C8H10O2 | 详情 | 详情 |
| (II) | 49860 | (2,6-dimethoxyphenyl)lithium | C8H9LiO2 | 详情 | 详情 | |
| (III) | 32549 | 2,6-dimethoxyphenylboronic acid | 23112-96-1 | C8H11BO4 | 详情 | 详情 |
| (IV) | 26874 | methyl 2-bromo-5-nitrobenzoate | 6942-36-5 | C8H6BrNO4 | 详情 | 详情 |
| (V) | 49861 | methyl 2',6'-dimethoxy-4-nitro[1,1'-biphenyl]-2-carboxylate | C16H15NO6 | 详情 | 详情 | |
| (VI) | 49862 | 1-hydroxy-8-nitro-6H-benzo[c]chromen-6-one | C13H7NO5 | 详情 | 详情 | |
| (VII) | 49863 | 1-methoxy-8-nitro-6H-benzo[c]chromen-6-one | C14H9NO5 | 详情 | 详情 | |
| (VIII) | 49864 | 8-amino-1-methoxy-6H-benzo[c]chromen-6-one | C14H11NO3 | 详情 | 详情 | |
| (IX) | 49865 | 10-methoxy-2,2,4-trimethyl-1,2-dihydro-5H-chromeno[3,4-f]quinolin-5-one | C20H19NO3 | 详情 | 详情 | |
| (X) | 62365 | 10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinolin-5-ol | C20H21NO3 | 详情 | 详情 | |
| (XI) | 62366 | 10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinolin-5-yl methyl ether; 5,10-dimethoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinoline | C21H23NO3 | 详情 | 详情 | |
| (XII) | 61128 | C4H8 | 详情 | 详情 |