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【结 构 式】 
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【分子编号】21641 【品名】1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-allyl-3-isobutylbutanedioate 【CA登记号】 |
【 分 子 式 】C21H25F5O4 【 分 子 量 】436.419116 【元素组成】C 57.8% H 5.77% F 21.77% O 14.66% |
合成路线1
该中间体在本合成路线中的序号：(IV)Friedel Crafts acylation of indole (II) with tert-leucine N-carboxyanhydride (I) in the presence of AlCl3 gave aminoketone (III). Subsequent condensation of (III) with the succinate building block (IV) in DMF afforded succinamide (V). Further deprotection of the tert-butyl ester of (V) by treatment with trifluoroacetic acid provided carboxylic acid (VI), which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VII) in the presence of EDC and HOBt to yield, after desilylation, the target hydroxamic acid.
| 【1】 Sheppard, G.S.; Florjancic, A.S.; Giesler, J.R.; Xu, L.; Guo, Y.; Davidsen, S.K.; Marcotte, P.A.; Elmore, I.; Albert, D.H.; Terrance, J.M.; Bouska, J.J.; Goodfellow, C.L.; Morgan, D.W.; Summers, J.B.; Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors. Bioorg Med Chem Lett 1998, 8, 22, 3251. |
| 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) | 21638 | (4S)-4-(tert-butyl)-1,3-oxazolidine-2,5-dione | C7H11NO3 | 详情 | 详情 | |
| (II) | 15292 | Indole; 1H-indole | 120-72-9 | C8H7N | 详情 | 详情 |
| (III) | 21640 | (2S)-2-amino-1-(1H-indol-3-yl)-3,3-dimethyl-1-butanone | C14H18N2O | 详情 | 详情 | |
| (IV) | 21641 | 1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-allyl-3-isobutylbutanedioate | C21H25F5O4 | 详情 | 详情 | |
| (V) | 21642 | tert-butyl (2S)-2-[(1R)-1-([[(1S)-1-(1H-indol-3-ylcarbonyl)-2,2-dimethylpropyl]amino]carbonyl)-3-methylbutyl]-4-pentenoate | C29H42N2O4 | 详情 | 详情 | |
| (VI) | 21643 | (2S)-2-[(1R)-1-([[(1S)-1-(1H-indol-3-ylcarbonyl)-2,2-dimethylpropyl]amino]carbonyl)-3-methylbutyl]-4-pentenoic acid | C25H34N2O4 | 详情 | 详情 | |
| (VII) | 21644 | (Aminooxy)(tert-butyl)dimethylsilane; O-[tert-Butyl(dimethyl)silyl]hydroxylamine | 41879-39-4 | C6H17NOSi | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Friedel Crafts acylation of indole (II) with phenylalanine N-carboxyanhydride (I) in the presence of AlCl3 gave aminoketone (III). Subsequent condensation of (III) with the succinate building block (IV) in DMF afforded succinamide (V). Further deprotection of the tert-butyl ester of (V) by treatment with trifluoroacetic acid provided carboxylic acid (VI), which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VII) in the presence of EDC and HOBt to yield, after desilylation, the target hydroxamic acid.
| 【1】 Sheppard, G.S.; Florjancic, A.S.; Giesler, J.R.; Xu, L.; Guo, Y.; Davidsen, S.K.; Marcotte, P.A.; Elmore, I.; Albert, D.H.; Terrance, J.M.; Bouska, J.J.; Goodfellow, C.L.; Morgan, D.W.; Summers, J.B.; Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors. Bioorg Med Chem Lett 1998, 8, 22, 3251. |
| 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) | 21645 | (4S)-4-benzyl-1,3-oxazolidine-2,5-dione | 14825-82-2 | C10H9NO3 | 详情 | 详情 |
| (II) | 15292 | Indole; 1H-indole | 120-72-9 | C8H7N | 详情 | 详情 |
| (III) | 21647 | (2S)-2-amino-1-(1H-indol-3-yl)-3-phenyl-1-propanone | C17H16N2O | 详情 | 详情 | |
| (IV) | 21641 | 1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-allyl-3-isobutylbutanedioate | C21H25F5O4 | 详情 | 详情 | |
| (IV) | 21655 | 4-(tert-butyl) 1-(2,3,4,5,6-pentafluorophenyl) (2R,3S)-2-isobutyl-3-(4-pentenyl)butanedioate | C23H29F5O4 | 详情 | 详情 | |
| (V) | 21649 | tert-butyl (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-(1H-indol-3-yl)-2-oxoethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoate | C32H40N2O4 | 详情 | 详情 | |
| (V) | 21656 | tert-butyl (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-(1H-indol-3-yl)-2-oxoethyl]amino]carbonyl)-3-methylbutyl]-6-heptenoate | C34H44N2O4 | 详情 | 详情 | |
| (VI) | 21650 | (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-(1H-indol-3-yl)-2-oxoethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoic acid | C28H32N2O4 | 详情 | 详情 | |
| (VI) | 21657 | (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-(1H-indol-3-yl)-2-oxoethyl]amino]carbonyl)-3-methylbutyl]-6-heptenoic acid | C30H36N2O4 | 详情 | 详情 | |
| (VII) | 21644 | (Aminooxy)(tert-butyl)dimethylsilane; O-[tert-Butyl(dimethyl)silyl]hydroxylamine | 41879-39-4 | C6H17NOSi | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)Condensation of N-(tert-butoxycarbonyl)phenylalanine (I) with phenyllithium furnished ketone (II). The N-Boc group of (II) was deprotected with HCl in dioxan to yield aminoketone (III), which was then condensed with the succinate building block (IV) in DMF to afford succinamide (V). Further deprotection of the tert-butyl ester of (V) by treatment with trifluoroacetic acid provided carboxylic acid (VI), which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VII) in the presence of EDC and HOBt to yield, after desilylation, the target hydroxamic acid.
| 【1】 Sheppard, G.S.; Florjancic, A.S.; Giesler, J.R.; Xu, L.; Guo, Y.; Davidsen, S.K.; Marcotte, P.A.; Elmore, I.; Albert, D.H.; Terrance, J.M.; Bouska, J.J.; Goodfellow, C.L.; Morgan, D.W.; Summers, J.B.; Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors. Bioorg Med Chem Lett 1998, 8, 22, 3251. |
| 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) | 12874 | (2R)-2-[(tert-Butoxycarbonyl)amino]-3-phenylpropionic acid; N-alpha-t-BOC-L-Phenylalanine | 13734-34-4 | C14H19NO4 | 详情 | 详情 |
| (II) | 21667 | tert-butyl (1S)-1-benzyl-2-oxo-2-phenylethylcarbamate | 202861-97-0 | C20H23NO3 | 详情 | 详情 |
| (III) | 21668 | (2S)-2-amino-1,3-diphenyl-1-propanone hydrochloride | C15H16ClNO | 详情 | 详情 | |
| (IV) | 21641 | 1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-allyl-3-isobutylbutanedioate | C21H25F5O4 | 详情 | 详情 | |
| (V) | 21670 | tert-butyl (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-oxo-2-phenylethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoate | C30H39NO4 | 详情 | 详情 | |
| (VI) | 21671 | (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-oxo-2-phenylethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoic acid | C26H31NO4 | 详情 | 详情 | |
| (VII) | 21644 | (Aminooxy)(tert-butyl)dimethylsilane; O-[tert-Butyl(dimethyl)silyl]hydroxylamine | 41879-39-4 | C6H17NOSi | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(V)Condensation of N-(tert-butoxycarbonyl)phenylalanine methyl ester (I) with pyrrolyl magnesium bromide (generated from pyrrole (II) and MeMgBr) furnished ketone (III). The N-Boc group of (III) was deprotected with HCl in dioxan to yield aminoketone (IV), which was then condensed with the succinate building block (V) in DMF to afford succinamide (VI). Further deprotection of the tert-butyl ester of (VI) by treatment with trifluoroacetic acid provided carboxylic acid (VII), which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VIII) in the presence of EDC and HOBt to yield, after desilylation, the target hydroxamic acid.
| 【1】 Sheppard, G.S.; Florjancic, A.S.; Giesler, J.R.; Xu, L.; Guo, Y.; Davidsen, S.K.; Marcotte, P.A.; Elmore, I.; Albert, D.H.; Terrance, J.M.; Bouska, J.J.; Goodfellow, C.L.; Morgan, D.W.; Summers, J.B.; Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors. Bioorg Med Chem Lett 1998, 8, 22, 3251. |
| 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) | 21673 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate | C15H21NO4 | 详情 | 详情 | |
| (II) | 21674 | 1H-pyrrole | 109-97-7 | C4H5N | 详情 | 详情 |
| (III) | 21675 | tert-butyl (1S)-1-benzyl-2-oxo-2-(1H-pyrrol-2-yl)ethylcarbamate | C18H22N2O3 | 详情 | 详情 | |
| (IV) | 21676 | (2S)-2-amino-3-phenyl-1-(1H-pyrrol-2-yl)-1-propanone hydrochloride | C13H15ClN2O | 详情 | 详情 | |
| (V) | 21641 | 1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-allyl-3-isobutylbutanedioate | C21H25F5O4 | 详情 | 详情 | |
| (VI) | 21678 | tert-butyl (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoate | C28H38N2O4 | 详情 | 详情 | |
| (VII) | 21679 | (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoic acid | C24H30N2O4 | 详情 | 详情 | |
| (VIII) | 21644 | (Aminooxy)(tert-butyl)dimethylsilane; O-[tert-Butyl(dimethyl)silyl]hydroxylamine | 41879-39-4 | C6H17NOSi | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(V)Condensation of N-(tert-butoxycarbonyl)phenylalanine methyl ester (I) with 2-thienyllithium (II) in THF at -78 C furnished racemized ketone (III). The N-Boc group of (III) was deprotected with HCl in dioxan to yield aminoketone (IV), which was then condensed with the succinate building block (V) in DMF to afford succinamide (VI). Further deprotection of the tert-butyl ester of (VI) by treatment with trifluoroacetic acid provided carboxylic acid (VII), which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VIII) in the presence of EDC and HOBt to yield, after desilylation, the target hydroxamic acid.
| 【1】 Sheppard, G.S.; Florjancic, A.S.; Giesler, J.R.; Xu, L.; Guo, Y.; Davidsen, S.K.; Marcotte, P.A.; Elmore, I.; Albert, D.H.; Terrance, J.M.; Bouska, J.J.; Goodfellow, C.L.; Morgan, D.W.; Summers, J.B.; Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors. Bioorg Med Chem Lett 1998, 8, 22, 3251. |
| 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) | 21673 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate | C15H21NO4 | 详情 | 详情 | |
| (II) | 21682 | 2-thienyllithium | 2786-07-4 | C4H3LiS | 详情 | 详情 |
| (III) | 21683 | tert-butyl 1-benzyl-2-oxo-2-(2-thienyl)ethylcarbamate | C18H21NO3S | 详情 | 详情 | |
| (IV) | 21684 | 2-amino-3-phenyl-1-(2-thienyl)-1-propanone hydrochloride | C13H14ClNOS | 详情 | 详情 | |
| (V) | 21641 | 1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-allyl-3-isobutylbutanedioate | C21H25F5O4 | 详情 | 详情 | |
| (VI) | 21686 | tert-butyl (2S)-2-[(1R)-1-([[1-benzyl-2-oxo-2-(2-thienyl)ethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoate | C28H37NO4S | 详情 | 详情 | |
| (VII) | 21687 | (2S)-2-[(1R)-1-([[1-benzyl-2-oxo-2-(2-thienyl)ethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoic acid | C24H29NO4S | 详情 | 详情 | |
| (VIII) | 21644 | (Aminooxy)(tert-butyl)dimethylsilane; O-[tert-Butyl(dimethyl)silyl]hydroxylamine | 41879-39-4 | C6H17NOSi | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(V)Condensation of N-(tert-butoxycarbonyl)phenylalanine methyl ester (I) with 2-oxazolyllithium (II) in THF at -78 C furnished racemized ketone (III). The N-Boc group of (III) was deprotected with HCl in dioxan to yield aminoketone (IV), which was then condensed with the succinate building block (V) in DMF to afford succinamide (VI). Further deprotection of the tert-butyl ester of (VI) by treatment with trifluoroacetic acid provided carboxylic acid (VII), which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VIII) in the presence of EDC and HOBt to yield, after desilylation, the target hydroxamic acid.
| 【1】 Sheppard, G.S.; Florjancic, A.S.; Giesler, J.R.; Xu, L.; Guo, Y.; Davidsen, S.K.; Marcotte, P.A.; Elmore, I.; Albert, D.H.; Terrance, J.M.; Bouska, J.J.; Goodfellow, C.L.; Morgan, D.W.; Summers, J.B.; Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors. Bioorg Med Chem Lett 1998, 8, 22, 3251. |
| 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) | 21673 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate | C15H21NO4 | 详情 | 详情 | |
| (II) | 21690 | 1,3-oxazol-2-yllithium | C3H2LiNO | 详情 | 详情 | |
| (III) | 21691 | tert-butyl 1-benzyl-2-(1,3-oxazol-2-yl)-2-oxoethylcarbamate | C17H20N2O4 | 详情 | 详情 | |
| (IV) | 21692 | 2-amino-1-(1,3-oxazol-2-yl)-3-phenyl-1-propanone hydrochloride | C12H13ClN2O2 | 详情 | 详情 | |
| (V) | 21641 | 1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-allyl-3-isobutylbutanedioate | C21H25F5O4 | 详情 | 详情 | |
| (VI) | 21694 | tert-butyl (2S)-2-[(1R)-1-([[1-benzyl-2-(1,3-oxazol-2-yl)-2-oxoethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoate | C27H36N2O5 | 详情 | 详情 | |
| (VII) | 21695 | (2S)-2-[(1R)-1-([[1-benzyl-2-(1,3-oxazol-2-yl)-2-oxoethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoic acid | C23H28N2O5 | 详情 | 详情 | |
| (VIII) | 21644 | (Aminooxy)(tert-butyl)dimethylsilane; O-[tert-Butyl(dimethyl)silyl]hydroxylamine | 41879-39-4 | C6H17NOSi | 详情 | 详情 |