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【结 构 式】 
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【分子编号】22266 【品名】2-(dichloromethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 【CA登记号】 |
【 分 子 式 】C7H13BCl2O2 【 分 子 量 】210.89542 【元素组成】C 39.87% H 6.21% B 5.13% Cl 33.62% O 15.17% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Hydrogenolysis of the benzyl ester of (XIII) over Pd/C gave peptide acid (XIV), which was converted to the mixed anhydride (XV) using isobutyl chloroformate and N-methylmorpholine. (Aminobutenyl)- dioxaborolane (XIX) was obtained by treatment of the (dichloromethyl)dioxaborolane (XVI) with allylmagnesium bromide (XVII), and subsequent displacement of the remaining chlorine atom with lithium bis(trimethylsilyl)amide. Condensation of anhydride (XV) with racemic aminoborolane (XIX) produced (XX) as a diastereomeric mixture. Finally, removal of the tert-butyl esters and hydrolysis of the dioxaborolane to the target boronic acid was effected with trifluoroacetic acid in CH2Cl2.
| 【1】 Attwood, M.R.; Campbell, A.D.; Bennett, J.M.; et al.; The design and synthersis of potent inhibitors of hepatitis C virus NS3-4A proteinase. Antivir Chem Chemother 1999, 10, 5, 259. |
| 【2】 Attwood, M.R.; Hurst, D.N.; Jones, P.S.; Kay, P.B.; Raynham, T.M.; Wilson, F.X. (F. Hoffmann-La Roche AG); Antiviral peptide derivs.. JP 2000508344; WO 9822496 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 22263 | 1-benzyl 19-(tert-butyl) (2S,5S,8S,11S,14S)-14-[2-(tert-butoxy)-2-oxoethyl]-11-[3-(tert-butoxy)-3-oxopropyl]-5-(tert-butyl)-2-isobutyl-8-(2-methylbenzyl)-4,7,10,13,16-pentaoxo-3,6,9,12,15-pentaazanonadecane-1,19-dioate | C54H81N5O13 | 详情 | 详情 | |
| (XIV) | 22264 | (2S,5S,8S,11S,14S)-14-[2-(tert-butoxy)-2-oxoethyl]-11-[3-(tert-butoxy)-3-oxopropyl]-5-(tert-butyl)-2-isobutyl-21,21-dimethyl-8-(2-methylbenzyl)-4,7,10,13,16,19-hexaoxo-20-oxa-3,6,9,12,15-pentaazadocosan-1-oic acid | C47H75N5O13 | 详情 | 详情 | |
| (XV) | 22265 | 4-Tert-butoxysuccinyl-(4-O-tert-butyl)-L-aspartyl-(5-O-tert-butyl)-L-glutamyl-(2-methyl)-L-phenylalanyl-L-tert-leucyl-L-leucine isobutoxycarbonyl anhydride; 4-Tert-butoxysuccinyl-(4-O-tert-butyl)-L-aspartyl-(5-O-tert-butyl)-L-glutamyl-(2-methyl)-L-phenylalanyl-L-tert-leucyl-L-leucine isobutoxycarbonyl anhydride | C52H83N5O15 | 详情 | 详情 | |
| (XVI) | 22266 | 2-(dichloromethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane | C7H13BCl2O2 | 详情 | 详情 | |
| (XVII) | 10386 | Allyl(bromo)magnesium | 1730-25-2 | C3H5BrMg | 详情 | 详情 |
| (XVIII) | 22272 | 2-(1-chloro-3-butenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane | C10H18BClO2 | 详情 | 详情 | |
| (XIX) | 65180 | 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-butenylamine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-buten-1-amine | C10H20BNO2 | 详情 | 详情 | |
| (XX) | 22274 | tert-butyl (6S,9S,12S,15S,18S)-6-[2-(tert-butoxy)-2-oxoethyl]-9-[3-(tert-butoxy)-3-oxopropyl]-15-(tert-butyl)-18-isobutyl-12-(2-methylbenzyl)-4,7,10,13,16,19-hexaoxo-21-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,8,11,14,17,20-hexaaza-23-tetracosen-1-oate | C57H93BN6O14 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVI)Hydrogenolysis of the benzyl ester of (XIII) over Pd/C gave peptide acid (XIV), which was converted to the mixed anhydride (XV) using isobutyl chloroformate and N-methylmorpholine. (Aminopropyl)- dioxaborolane (XIX) was obtained by treatment of the (dichloromethyl)dioxaborolane (XVI) with ethylmagnesium bromide (XVII), and subsequent displacement of the remaining chlorine atom with lithium bis(trimethylsilyl)amide. Condensation of anhydride (XV) with racemic aminoborolane (XIX) produced (XX) as a diastereomeric mixture. Finally, removal of the tert-butyl esters and hydrolysis of the dioxaborolane to the target boronic acid was effected with trifluoroacetic acid in CH2Cl2.
| 【1】 Attwood, M.R.; Campbell, A.D.; Bennett, J.M.; et al.; The design and synthersis of potent inhibitors of hepatitis C virus NS3-4A proteinase. Antivir Chem Chemother 1999, 10, 5, 259. |
| 【2】 Attwood, M.R.; Hurst, D.N.; Jones, P.S.; Kay, P.B.; Raynham, T.M.; Wilson, F.X. (F. Hoffmann-La Roche AG); Antiviral peptide derivs.. JP 2000508344; WO 9822496 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 22264 | (2S,5S,8S,11S,14S)-14-[2-(tert-butoxy)-2-oxoethyl]-11-[3-(tert-butoxy)-3-oxopropyl]-5-(tert-butyl)-2-isobutyl-21,21-dimethyl-8-(2-methylbenzyl)-4,7,10,13,16,19-hexaoxo-20-oxa-3,6,9,12,15-pentaazadocosan-1-oic acid | C47H75N5O13 | 详情 | 详情 | |
| (XV) | 22265 | 4-Tert-butoxysuccinyl-(4-O-tert-butyl)-L-aspartyl-(5-O-tert-butyl)-L-glutamyl-(2-methyl)-L-phenylalanyl-L-tert-leucyl-L-leucine isobutoxycarbonyl anhydride; 4-Tert-butoxysuccinyl-(4-O-tert-butyl)-L-aspartyl-(5-O-tert-butyl)-L-glutamyl-(2-methyl)-L-phenylalanyl-L-tert-leucyl-L-leucine isobutoxycarbonyl anhydride | C52H83N5O15 | 详情 | 详情 | |
| (XVI) | 22266 | 2-(dichloromethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane | C7H13BCl2O2 | 详情 | 详情 | |
| (XVII) | 22267 | (bromomethyl)(ethyl)magnesium | C3H7BrMg | 详情 | 详情 | |
| (XVIII) | 22268 | 2-(1-chloropropyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane | C9H18BClO2 | 详情 | 详情 | |
| (XIX) | 22269 | 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-propanamine; 1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propylamine | C9H20BNO2 | 详情 | 详情 | |
| (XX) | 22270 | tert-butyl (6S,9S,12S,15S,18S)-18-[2-(tert-butoxy)-2-oxoethyl]-15-[3-(tert-butoxy)-3-oxopropyl]-9-(tert-butyl)-6-isobutyl-12-(2-methylbenzyl)-5,8,11,14,17,20-hexaoxo-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4,7,10,13,16,19-hexaazatricosan-23-oate | C56H93BN6O14 | 详情 | 详情 |