2,3,5,6-Tetrafluorophenol -Drug Synthesis Database

【结构式】

【分子编号】49986

【品名】2,3,5,6-Tetrafluorophenol

【CA登记号】769-39-1

【分子式】C₆H₂F₄O

【分子量】166.0748928

【元素组成】C 43.39% H 1.21% F 45.76% O 9.63%

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：(VI)

Aspartic acid beta-tert-butyl ester (II) was silylated using bis(trimethylsilyl)acetamide and subsequently coupled with the hydroxysuccinimidyl ester of Z-valine (I) to furnish dipeptide (III) (1). This was converted to the corresponding mixed anhydride (IV) with isobutyl chloroformate and N-methylmorpholine. Reaction of anhydride (IV) with ethereal diazomethane, followed by treatment of the intermediate diazo ketone with HBr in HOAc, gave rise to the bromo ketone (V). Tetrafluorophenol (VI) was alkylated with bromide (V) to yield ether (VII). The ketone function of (VII) was then reduced to alcohol (VIII) employing NaBH4. Further hydrogenolysis of the benzyloxycarbonyl group of (VIII) provided amine (IX).

参考文献中间体

合成目标

【1】 Ternansky, R.J.; et al.; Structure-activity relationship of a series of oxamyl dipeptide caspase inhibitors developed for the treatment of stroke. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 75.
【2】 Karanewsky, D.S.; Ternansky, R.J. (Idun Pharmaceuticals, Inc.); C-Terminal modified oxamyl dipeptides as inhibitors of the ICE/ced-3 family of cysteine proteases. EP 1091930; WO 0001666 .

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)	49982	benzyl (1S)-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-2-methylpropylcarbamate		C₁₇H₂₀N₂O₆	详情	详情
(II)	26564	(2S)-2-amino-4-(tert-butoxy)-4-oxobutyric acid	3057-74-7	C₈H₁₅NO₄	详情	详情
(III)	49983	(2S)-2-[((2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)amino]-4-(tert-butoxy)-4-oxobutyric acid		C₂₁H₃₀N₂O₇	详情	详情
(IV)	49984			C₂₆H₃₈N₂O₉	详情	详情
(V)	49985	tert-butyl (3S)-3-[((2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)amino]-5-bromo-4-oxopentanoate		C₂₂H₃₁BrN₂O₆	详情	详情
(VI)	49986	2,3,5,6-Tetrafluorophenol	769-39-1	C₆H₂F₄O	详情	详情
(VII)	49987	tert-butyl (3S)-3-[((2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)amino]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoate		C₂₈H₃₂F₄N₂O₇	详情	详情
(VIII)	49988	tert-butyl (3S)-3-[((2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoyl)amino]-4-hydroxy-5-(2,3,5,6-tetrafluorophenoxy)pentanoate		C₂₈H₃₄F₄N₂O₇	详情	详情
(IX)	49989	tert-butyl (3S)-3-[[(2S)-2-amino-3-methylbutanoyl]amino]-4-hydroxy-5-(2,3,5,6-tetrafluorophenoxy)pentanoate		C₂₀H₂₈F₄N₂O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVIII)

Coupling of the succinimidyl ester of protected glutamic acid (XVI) with glutamic acid gamma-tert-butyl ester (XV) provided the protected dipeptide (XVII), which was then activated with tetrafluorophenol (XVIII) by means of EDC in DMF to yield the tetrafluorophenyl ester (XIX). Condensation of (XIX) with amine (XIV) produced amide (XX), whose N-benzyloxycarbonyl group was then removed by hydrogenolysis over Pd/C to yield amine (XXI).

参考文献中间体

合成目标

【1】 Rajopadhye, M.; Harris, T.D.; Cheesman, E.H. (DuPont Pharmaceuticals Co.); Vitronectin receptor antagonist pharmaceuticals. WO 0035488 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	51008	(2S)-2-[[(4-[4-[(2-aminoethyl)amino]-4-oxobutoxy]-2,6-dimethylphenyl)sulfonyl]amino]-3-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]propionic acid		C₃₁H₄₁N₉O₇S	详情	详情
(XV)	51009	(2S)-2-amino-5-(tert-butoxy)-5-oxopentanoic acid		C₉H₁₇NO₄	详情	详情
(XVI)	51010	tert-butyl (4S)-4-[[(benzyloxy)carbonyl]amino]-5-[(2,5-dioxo-1-pyrrolidinyl)oxy]-5-oxopentanoate		C₂₁H₂₆N₂O₈	详情	详情
(XVII)	51011	(2S)-2-[[(2S)-2-[[(benzyloxy)carbonyl]amino]-5-(tert-butoxy)-5-oxopentanoyl]amino]-5-(tert-butoxy)-5-oxopentanoic acid		C₂₆H₃₈N₂O₉	详情	详情
(XVIII)	49986	2,3,5,6-Tetrafluorophenol	769-39-1	C₆H₂F₄O	详情	详情
(XIX)	51012	5-(tert-butyl) 1-(2,3,5,6-tetrafluorophenyl) (2S)-2-[[(2S)-2-[[(benzyloxy)carbonyl]amino]-5-(tert-butoxy)-5-oxopentanoyl]amino]pentanedioate		C₃₂H₃₈F₄N₂O₉	详情	详情
(XX)	51013	(2S)-2-([[4-([(10S,13S)-10,13-bis[3-(tert-butoxy)-3-oxopropyl]-4,9,12,15-tetraoxo-17-phenyl-16-oxa-5,8,11,14-tetraazaheptadec-1-yl]oxy)-2,6-dimethylphenyl]sulfonyl]amino)-3-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]propionic acid		C₅₇H₇₇N₁₁O₁₅S	详情	详情
(XXI)	51021	(2S)-2-([[4-([(10S,13S)-13-amino-10-[3-(tert-butoxy)-3-oxopropyl]-18,18-dimethyl-4,9,12,16-tetraoxo-17-oxa-5,8,11-triazanonadec-1-yl]oxy)-2,6-dimethylphenyl]sulfonyl]amino)-3-[([1-[3-(1H-imidazol-2-ylamino)propyl]-1H-indazol-5-yl]carbonyl)amino]propionic acid		C₄₉H₇₁N₁₁O₁₃S	详情	详情

Extended Information