【结 构 式】 |
【分子编号】60792 【品名】benzyl (Z)-{4-[(2S)-2-[((2R,3S)-3-{[(benzyloxy)amino]carbonyl}-2-isobutyl-6-phenylhexanoyl)amino]-3-(methylamino)-3-oxopropyl]anilino}{[(benzyloxy)carbonyl]amino}methylidenecarbamate 【CA登记号】 |
【 分 子 式 】C51H58N6O8 【 分 子 量 】883.05716 【元素组成】C 69.37% H 6.62% N 9.52% O 14.49% |
合成路线1
该中间体在本合成路线中的序号:(XIV)N-Boc-L-4'-Aminophenylalanine-N-methylamide (VIII) was converted to the guanidine derivative (X) by reaction with pyrazole-N,N'-bis(benzyloxycarbonyl)carboxamidine (IX). After acidic Boc group cleavage in (IX), the resultant amino amide (XI) was coupled with the carboxylic acid (VII) to produce a diastereomeric mixture of amides, which were separated by column chromatography. The desired isomer (XII) was then treated with 95% aqueous trifluoroacetic acid to remove the tert-butyl ester group, yielding acid (XIII). Coupling of (XIII) with O-benzyl hydroxylamine furnished the O-benzyl hydroxamate (XIV). Finally, the benzyl and benzyloxycarbonyl protecting groups of (XIV) were removed by catalytic hydrogenation over Pd/C to afford the title compound.
【1】 Fujisawa, T.; Odake, S.; Morita, Y.; Hongo, T.; Ito, H.; Yasuda, J.; Suda, E.; Igeta, K.; Morikawa, T. (Fuji Yakuhin Kogyo Co., Ltd.); Highly water-soluble metalloproteinase inhibitor. EP 0832875; WO 9633968 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VII) | 60699 | (2R)-3-(tert-butoxycarbonyl)-2-isobutyl-6-phenylhexanoic acid | C21H32O4 | 详情 | 详情 | |
(VIII) | 60700 | tert-butyl (1S)-1-(4-aminobenzyl)-2-(methylamino)-2-oxoethylcarbamate | C15H23N3O3 | 详情 | 详情 | |
(IX) | 60787 | C6H10N4 | 详情 | 详情 | ||
(X) | 60788 | benzyl (Z)-{[(benzyloxy)carbonyl]amino}{4-[(2S)-2-[(tert-butoxycarbonyl)amino]-3-(methylamino)-3-oxopropyl]anilino}methylidenecarbamate | C32H37N5O7 | 详情 | 详情 | |
(XI) | 60789 | benzyl (Z)-{4-[(2S)-2-amino-3-(methylamino)-3-oxopropyl]anilino}{[(benzyloxy)carbonyl]amino}methylidenecarbamate | C27H29N5O5 | 详情 | 详情 | |
(XII) | 60790 | tert-butyl (2S,3R)-3-({[(1S)-1-{4-[({[(benzyloxy)carbonyl]amino}{[(benzyloxy)carbonyl]imino}methyl)amino]benzyl}-2-(methylamino)-2-oxoethyl]amino}carbonyl)-5-methyl-2-(3-phenylpropyl)hexanoate | C48H59N5O8 | 详情 | 详情 | |
(XIII) | 60791 | (2S,3R)-3-({[(1S)-1-{4-[({[(benzyloxy)carbonyl]amino}{[(benzyloxy)carbonyl]imino}methyl)amino]benzyl}-2-(methylamino)-2-oxoethyl]amino}carbonyl)-5-methyl-2-(3-phenylpropyl)hexanoic acid | C44H51N5O8 | 详情 | 详情 | |
(XIV) | 60792 | benzyl (Z)-{4-[(2S)-2-[((2R,3S)-3-{[(benzyloxy)amino]carbonyl}-2-isobutyl-6-phenylhexanoyl)amino]-3-(methylamino)-3-oxopropyl]anilino}{[(benzyloxy)carbonyl]amino}methylidenecarbamate | C51H58N6O8 | 详情 | 详情 |