(4S)-4-(tert-butyl)-1,3-oxazolidine-2,5-dione -Drug Synthesis Database

【结构式】

【分子编号】21638

【品名】(4S)-4-(tert-butyl)-1,3-oxazolidine-2,5-dione

【CA登记号】

【分子式】C₇H₁₁NO₃

【分子量】157.16928

【元素组成】C 53.49% H 7.05% N 8.91% O 30.54%

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：(I)

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.

参考文献中间体

合成目标

【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：(I)

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 malate building block (IV) in DMF afforded amide (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.

参考文献中间体

合成目标

【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)	21662	1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-hydroxy-3-isobutylbutanedioate		C₁₈H₂₁F₅O₅	详情	详情
(V)	21663	tert-butyl (2S,3R)-2-hydroxy-3-([[(1S)-1-(1H-indol-3-ylcarbonyl)-2,2-dimethylpropyl]amino]carbonyl)-5-methylhexanoate		C₂₆H₃₈N₂O₅	详情	详情
(VI)	21664	(2S,3R)-2-hydroxy-3-([[(1S)-1-(1H-indol-3-ylcarbonyl)-2,2-dimethylpropyl]amino]carbonyl)-5-methylhexanoic acid		C₂₂H₃₀N₂O₅	详情	详情
(VII)	21644	(Aminooxy)(tert-butyl)dimethylsilane; O-[tert-Butyl(dimethyl)silyl]hydroxylamine	41879-39-4	C₆H₁₇NOSi	详情	详情

Extended Information