methyl 3-(4-[[(2S)-2-(hydroxymethyl)pyrrolidinyl]carbonyl]-2-methoxy-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]phenoxy)propanoate -Drug Synthesis Database

【结构式】

【分子编号】26885

【品名】methyl 3-(4-[[(2S)-2-(hydroxymethyl)pyrrolidinyl]carbonyl]-2-methoxy-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]phenoxy)propanoate

【CA登记号】

【分子式】C₂₀H₂₅Cl₃N₂O₈

【分子量】527.78528

【元素组成】C 45.51% H 4.77% Cl 20.15% N 5.31% O 24.25%

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：(VII)

Reaction of vanillic acid (I) with 3-bromopropanol gave ether (II). Subsequent nitration of (II) with simultaneous oxidation of the primary alcohol employing nitric acid afforded the nitro diacid (IV), which by chemoselective esterification in the presence of a catalytic amount of p-toluenesulfonic acid yielded monoester (IV). After conversion of (IV) to the acid chloride upon treatment with oxalyl chloride, coupling with (S)-2-(hydroxymethyl)pyrrolidine (V) gave amide (VI). Catalytic hydrogenation of the nitro group of (VI), followed by protection of the intermediate aniline with 2,2,2-trichloroethyl chloroformate provided carbamate (VII). Further Swern oxidation of the alcohol group of (VII) with concomitant cyclization generated the pyrrolobenzodiazepine (VIII). The methyl ester of (VIII) was then hydrolyzed to carboxylic acid (IX).

参考文献中间体

合成目标

【1】 Baraldi, P.G.; Cacciari, B.; Guiotto, A.; Leoni, A.; Romagnoli, R.; Spalluto, G.; Mongelli, N.; Howard, P.W.; Thurston, D.E.; Bianchi, N.; Gambari, R.; Design, synthesis and biological activity of a pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-distamycin hybrid. Bioorg Med Chem Lett 1998, 8, 21, 3019.
【2】 Cacciari, B.; Baraldi, P.G.; Balboni, G.; et al.; Synthesis, in vitro antiproliferative activity, and DNA-binding properties of hybrid molecules containing pyrrolo[2,1-c][1,4]benzodiazepine and minor-groove-binding oligopyrrole carriers. J Med Chem 1999, 42, 25, 5131.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	12573	3-Bromo-1-propanol; 3-Bromopropanol	627-18-9	C₃H₇BrO	详情	详情
(I)	17786	4-hydroxy-3-methoxybenzoic acid; Vanillic acid	121-34-6	C₈H₈O₄	详情	详情
(II)	26881	4-(3-hydroxypropoxy)-3-methoxybenzoic acid		C₁₁H₁₄O₅	详情	详情
(III)	26882	4-(2-carboxyethoxy)-5-methoxy-2-nitrobenzoic acid		C₁₁H₁₁NO₈	详情	详情
(IV)	26883	5-methoxy-4-(3-methoxy-3-oxopropoxy)-2-nitrobenzoic acid		C₁₂H₁₃NO₈	详情	详情
(V)	21347	(2S)pyrrolidinylmethanol	23356-96-9	C₅H₁₁NO	详情	详情
(VI)	26884	methyl 3-(4-[[(2S)-2-(hydroxymethyl)pyrrolidinyl]carbonyl]-2-methoxy-5-nitrophenoxy)propanoate		C₁₇H₂₂N₂O₈	详情	详情
(VII)	26885	methyl 3-(4-[[(2S)-2-(hydroxymethyl)pyrrolidinyl]carbonyl]-2-methoxy-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]phenoxy)propanoate		C₂₀H₂₅Cl₃N₂O₈	详情	详情
(VIII)	26886	2,2,2-trichloroethyl (11S,11aS)-11-hydroxy-7-methoxy-8-(3-methoxy-3-oxopropoxy)-5-oxo-2,3,11,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate		C₂₀H₂₃Cl₃N₂O₈	详情	详情
(IX)	26887	3-([(11S,11aS)-11-hydroxy-7-methoxy-5-oxo-10-[(2,2,2-trichloroethoxy)carbonyl]-2,3,5,10,11,11a-hexahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl]oxy)propionic acid		C₁₉H₂₁Cl₃N₂O₈	详情	详情

Extended Information