　 -Drug Synthesis Database

【结构式】

【分子编号】60787

【品名】　

【CA登记号】

【分子式】C₆H₁₀N₄

【分子量】138.17236

【元素组成】C 52.16% H 7.29% N 40.55%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IX)

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.

参考文献中间体

合成目标

【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	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

合成路线2

该中间体在本合成路线中的序号：(VII)

The N-Boc group of the orthogonally protected beta-lysine (I) is removed by acidic treatment to provide amine (II), which is further reprotected as the trifluoroacetamide (III) by reaction with methyl trifluoroacetate. Transesterification of acid (III) with t-butyl acetate in the presence of HClO4 gives rise to the corresponding t-butyl ester (IV). Selective methylation of the trifluoroacetamide N of (IV) furnishes the N-methyl amide (V), which is subsequently hydrolyzed to the N-methyl amine (VI) under alkaline conditions. Guanidylation of amine (VI) with N,N'-bis-carbobenzoxy-1-amidinopyrazole (VII) leads to the protected guanidine (VIII). Then, acidic cleavage of the tert-butyl ester group of (VIII) provides carboxylic acid (IX)

参考文献中间体

合成目标

【1】 Brands, M.; Endermann, R.; Gahlmann, R.; et al.; Novel antibiotics for the treatment of gram-positive bacterial infections. J Med Chem 2002, 45, 19, 4246.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	62268	(3S)-3-{[(benzyloxy)carbonyl]amino}-6-[(tert-butoxycarbonyl)amino]hexanoic acid	C₁₉H₂₈N₂O₆	详情	详情
(II)	62269	(3S)-6-amino-3-{[(benzyloxy)carbonyl]amino}hexanoic acid	C₁₄H₂₀N₂O₄	详情	详情
(III)	62270	(3S)-3-{[(benzyloxy)carbonyl]amino}-6-[(2,2,2-trifluoroacetyl)amino]hexanoic acid	C₁₆H₁₉F₃N₂O₅	详情	详情
(IV)	62271	tert-butyl (3S)-3-{[(benzyloxy)carbonyl]amino}-6-[(2,2,2-trifluoroacetyl)amino]hexanoate	C₂₀H₂₇F₃N₂O₅	详情	详情
(V)	62272	tert-butyl (3S)-3-{[(benzyloxy)carbonyl]amino}-6-[methyl(2,2,2-trifluoroacetyl)amino]hexanoate	C₂₁H₂₉F₃N₂O₅	详情	详情
(VI)	62273	tert-butyl (3S)-3-{[(benzyloxy)carbonyl]amino}-6-(methylamino)hexanoate	C₁₉H₃₀N₂O₄	详情	详情
(VII)	60787		C₆H₁₀N₄	详情	详情
(VIII)	62274	tert-butyl (3S)-3-{[(benzyloxy)carbonyl]amino}-6-[({[(benzyloxy)carbonyl]amino}{[(benzyloxy)carbonyl]imino}methyl)(methyl)amino]hexanoate	C₃₆H₄₄N₄O₈	详情	详情
(IX)	62275	(3S)-3-{[(benzyloxy)carbonyl]amino}-6-[({[(benzyloxy)carbonyl]amino}{[(benzyloxy)carbonyl]imino}methyl)(methyl)amino]hexanoic acid	C₃₂H₃₆N₄O₈	详情	详情

Extended Information