【结 构 式】 |
【分子编号】49188 【品名】(2R)-2-[2-(tert-butoxy)-2-oxoethyl]-4-pentenoic acid 【CA登记号】 |
【 分 子 式 】C11H18O4 【 分 子 量 】214.26152 【元素组成】C 61.66% H 8.47% O 29.87% |
合成路线1
该中间体在本合成路线中的序号:(V)Coupling of N-Boc-L-tert-leucine (I) with (R)-1-phenylethylamine (II) using EDC and HOBt gave amide (III) which, after acid cleavage of the N-Boc group, provided amino amide (IV). Acylation of amine (IV) with (R)-2-allylsuccinic acid 4-tert-butyl ester (V) afforded the diamide (VI). Biphenylyl bromide (IX) was prepared by the Suzuki coupling between 5-bromo-2-iodotoluene (VII) and phenylboronic acid (VIII). The biaryl group was then introduced via Heck reaction of biphenylyl bromide (IX) with olefin (VI), yielding adduct (X). Subsequent hydrogenation of the olefin double bond of (X) over Pd/C afforded (XI). Carboxylic acid (XII) was then obtained by trifluoroacetic acid-promoted cleavage of the tert-butyl ester group of (XI). Conversion of (XII) to the title hydroxamic acid was then achieved by coupling of carboxylic acid (XII) with O-allylhydroxylamine (XIII), followed by O-allyl group cleavage in the presence of ammonium formate and palladium catalyst.
【1】 Fray, M.J.; et al.; Discovery of potent and selective succinyl hydroxamate inhibitors of matrix metalloprotease-3 (stromelysin-1). 13th Noordwijkerhout-Camerino Symp Trends Drug Res (May 6 2001, Noordwijkerhout) 2001, Abst P8. |
【2】 Fray, M.J.; Dickinson, R.P.; Discovery of potent and selective succinyl hydroxamate inhibitors of matrix metalloprotease-3 (stromelysin-1). Bioorg Med Chem Lett 2001, 11, 4, 571. |
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) | 22251 | (2S)-2-[(tert-butoxycarbonyl)amino]-3,3-dimethylbutyric acid;2-((tert-butoxycarbonyl)amino)-3,3-dimethylbutanoic acid;N-(tert-butoxycarbonyl)-3-methyl-L-valine | 62965-35-9 | C11H21NO4 | 详情 | 详情 |
(II) | 10039 | (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine | 3886-69-9 | C8H11N | 详情 | 详情 |
(III) | 49186 | tert-butyl (1S)-2,2-dimethyl-1-([[(1R)-1-phenylethyl]amino]carbonyl)propylcarbamate | C19H30N2O3 | 详情 | 详情 | |
(IV) | 49187 | (2S)-2-amino-3,3-dimethyl-N-[(1R)-1-phenylethyl]butanamide | C14H22N2O | 详情 | 详情 | |
(V) | 49188 | (2R)-2-[2-(tert-butoxy)-2-oxoethyl]-4-pentenoic acid | C11H18O4 | 详情 | 详情 | |
(VI) | 49189 | tert-butyl (3R)-3-([[(1S)-2,2-dimethyl-1-([[(1R)-1-phenylethyl]amino]carbonyl)propyl]amino]carbonyl)-5-hexenoate | C25H38N2O4 | 详情 | 详情 | |
(VII) | 49190 | 1-Bromo-4-iodo-5-methylbenzene; 5-Bromo-2-iodotoluene | C7H6BrI | 详情 | 详情 | |
(VIII) | 16593 | Phenylboronic acid;Benzeneboronic acid;Phenylboron dihydroxide | 98-80-6 | C6H7BO2 | 详情 | 详情 |
(IX) | 49191 | 4-bromo-2-methyl-1,1'-biphenyl | C13H11Br | 详情 | 详情 | |
(X) | 49192 | tert-butyl (3R,5E)-3-([[(1S)-2,2-dimethyl-1-([[(1R)-1-phenylethyl]amino]carbonyl)propyl]amino]carbonyl)-6-(2-methyl[1,1'-biphenyl]-4-yl)-5-hexenoate | C38H48N2O4 | 详情 | 详情 | |
(XI) | 49193 | tert-butyl (3R)-3-([[(1S)-2,2-dimethyl-1-([[(1R)-1-phenylethyl]amino]carbonyl)propyl]amino]carbonyl)-6-(2-methyl[1,1'-biphenyl]-4-yl)hexanoate | C38H50N2O4 | 详情 | 详情 | |
(XII) | 49194 | (3R)-3-([[(1S)-2,2-dimethyl-1-([[(1R)-1-phenylethyl]amino]carbonyl)propyl]amino]carbonyl)-6-(2-methyl[1,1'-biphenyl]-4-yl)hexanoic acid | C34H42N2O4 | 详情 | 详情 | |
(XIII) | 49195 | 3-(aminooxy)-1-propene; O-allylhydroxylamine | C3H7NO | 详情 | 详情 |