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【结 构 式】

【分子编号】49192

【品名】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

【CA登记号】

【 分 子 式 】C38H48N2O4

【 分 子 量 】596.8102

【元素组成】C 76.48% H 8.11% N 4.69% O 10.72%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(X)

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
Extended Information