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【结 构 式】 
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【分子编号】41024 【品名】(3S)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-[2-[(methylsulfonyl)oxy]ethoxy]butyl methanesulfonate 【CA登记号】 |
【 分 子 式 】C24H36O8S2Si 【 分 子 量 】544.76254 【元素组成】C 52.92% H 6.66% O 23.5% S 11.77% Si 5.16% |
合成路线1
该中间体在本合成路线中的序号：(XXIV)The carbinol intermediate (XV) has also been obtained as follows: Alkylation of 4-(tert-butyldiphenylsilyloxy)-3(S)-hydroxybutyric acid methyl ester (XVIII) with allyl trichloroacetylimidate (XIX) and trifluoromethanesulfonic acid gives the allyl ether (XX), which is reduced with DIBAL in toluene to afford the alcohol (XXI). Ozonolysis of (XXI) with O3 in methanol provides the hydroxyaldehyde (XXII), which is reduced with NaBH4 in methanol, giving diol (XXIII). Reaction of (XXIII) with MsCl and TEA in ether yields the dimesylate (XXIV), which is treated with NaI in hot acetone to provide the diiodide (XXV). Cyclization of (XXV) with 3,4-bis(3-indolyl)-1-methyl-2,5-dihydro-1H-pyrrole-2,5-dione (XI) by means of Cs2CO3 in DMF gives the hexacyclic compound (XXVI), which is demethylated as before by reaction with KOH in refluxing ethanol to the hexacyclic furan derivative (XXVII) and then treated with HMDS in hot methanol to give the demethylated pyrrole derivative (XXVIII). Finally, this compound is desilylated with HCl to the carbinol (XV).
| 【1】 Sorbera, L.A.; Rabasseda, X.; Silvestre, J.S.; Castañer, J.; LY-333531 Mesylate Hydrate. Drugs Fut 2000, 25, 10, 1017-1026. |
| 【2】 Jirousek, M.R.; Gillig, J.R.; Gonzalez, C.M.; et al.; (S)-13-[(Dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16,21-dimetheno-1H,13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H)-dione (LY333531) and related analogues: Isozyme selective inhibitors of protein kinase Cbeta. J Med Chem 1996, 39, 14, 2664. |
| 【3】 Heath, W.F. Jr.; Jirousek, M.R.; McDonald, J.H. III; Rito, C.J. (Eli Lilly and Company); Protein kinase C inhibitors. CA 2137203; EP 0657458; JP 1995238044; US 5624949 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 41012 | 3,4-di(1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione | 113963-68-1 | C21H15N3O2 | 详情 | 详情 |
| (XV) | 41013 | (18S)-18-(hydroxymethyl)-17-oxa-4,14,21-triazahexacyclo[19.6.1.1(7,14).0(2,6).0(8,13).0(22,27)]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione | C26H23N3O4 | 详情 | 详情 | |
| (XVIII) | 41019 | methyl (3S)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-hydroxybutanoate | C21H28O4Si | 详情 | 详情 | |
| (XIX) | 22755 | allyl 2,2,2-trichloroethanimidoate | 51479-73-3 | C5H6Cl3NO | 详情 | 详情 |
| (XX) | 41020 | methyl (3S)-3-(allyloxy)-4-[[tert-butyl(diphenyl)silyl]oxy]butanoate | C24H32O4Si | 详情 | 详情 | |
| (XXI) | 41021 | (3S)-3-(allyloxy)-4-[[tert-butyl(diphenyl)silyl]oxy]-1-butanol | C23H32O3Si | 详情 | 详情 | |
| (XXII) | 41022 | 2-[[(1S)-1-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-hydroxypropyl]oxy]acetaldehyde | C22H30O4Si | 详情 | 详情 | |
| (XXIII) | 41023 | (3S)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-(2-hydroxyethoxy)-1-butanol | C22H32O4Si | 详情 | 详情 | |
| (XXIV) | 41024 | (3S)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-[2-[(methylsulfonyl)oxy]ethoxy]butyl methanesulfonate | C24H36O8S2Si | 详情 | 详情 | |
| (XXV) | 41025 | tert-butyl(diphenyl)silyl (2S)-4-iodo-2-(2-iodoethoxy)butyl ether; tert-butyl[[(2S)-4-iodo-2-(2-iodoethoxy)butyl]oxy]diphenylsilane | C22H30I2O2Si | 详情 | 详情 | |
| (XXVI) | 41026 | (18S)-18-([[tert-butyl(diphenyl)silyl]oxy]methyl)-4-methyl-17-oxa-4,14,21-triazahexacyclo[19.6.1.1(7,14).0(2,6).0(8,13).0(22,27)]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione | C43H43N3O4Si | 详情 | 详情 | |
| (XXVII) | 41027 | (18S)-18-([[tert-butyl(diphenyl)silyl]oxy]methyl)-4,17-dioxa-14,21-diazahexacyclo[19.6.1.1(7,14).0(2,6).0(8,13).0(22,27)]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione | C42H40N2O5Si | 详情 | 详情 | |
| (XXVIII) | 41028 | (18S)-18-([[tert-butyl(diphenyl)silyl]oxy]methyl)-17-oxa-4,14,21-triazahexacyclo[19.6.1.1(7,14).0(2,6).0(8,13).0(22,27)]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione | C42H41N3O4Si | 详情 | 详情 |