2-Trifluoromethylbenzeneboronic acid; 2-Trifluoromethylphenylboronic acid; o-Trifluoromethylphenylboronic acid -Drug Synthesis Database

【结构式】

【分子编号】53180

【品名】2-Trifluoromethylbenzeneboronic acid; 2-Trifluoromethylphenylboronic acid; o-Trifluoromethylphenylboronic acid

【CA登记号】1423-27-4

【分子式】C₇H₆BF₃O₂

【分子量】189.9296496

【元素组成】C 44.27% H 3.18% B 5.69% F 30.01% O 16.85%

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：(XX)

Condensation of carbonate (XIV) with N-alpha-Cbz-lysine methyl ester (XV) afforded the carbamate (XVI). The benzyl ester and N-Cbz protecting groups of (XVI) were then removed by catalytic hydrogenolysis, yielding amino acid (XVII), which was subjected to intramolecular cyclization in the presence of BOP to furnish the macrocyclic compound (XVIII). After conversion of the phenolic hydroxyl of (XVIII) to the aryl triflate (XIX), Suzuki coupling with 2-(trifluoromethyl)phenylboronic acid (XX) provided the biphenyl derivative (XXI).

参考文献中间体

合成目标

【1】 Xue, C.-B.; et al.; Discovery of macrocyclic hydroxamic acids containing biphenylmethyl derivatives at P1', a series of selective TNF-alpha converting enzyme inhibitors with potent cellular activity in the inhibition of TNF-alpha release. J Med Chem 2001, 44, 21, 3351.

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)	53175	1-benzyl 4-(tert-butyl) (2R,3S)-2-[4-(benzyloxy)benzyl]-3-(3-{[(4-nitrophenoxy)carbonyl]oxy}propyl)butanedioate	n/a	C₃₉H₄₁NO₁₀	详情	详情
(XV)	35087	methyl (2S)-6-amino-2-[[(benzyloxy)carbonyl]amino]hexanoate		C₁₅H₂₂N₂O₄	详情	详情
(XVI)	53176	17-benzyl 16-(tert-butyl) 5-methyl (5S,16S,17R)-18-[4-(benzyloxy)phenyl]-3,11-dioxo-1-phenyl-2,12-dioxa-4,10-diazaoctadecane-5,16,17-tricarboxylate	n/a	C₄₈H₅₈N₂O₁₁	详情	详情
(XVII)	53177	(2R,3S)-6-[({[(5S)-5-amino-6-methoxy-6-oxohexyl]amino}carbonyl)oxy]-3-(tert-butoxycarbonyl)-2-(4-hydroxybenzyl)hexanoic acid	n/a	C₂₆H₄₀N₂O₉	详情	详情
(XVIII)	53178	12-(tert-butyl) 8-methyl (8S,11R,12S)-11-(4-hydroxybenzyl)-2,10-dioxo-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxylate	n/a	C₂₆H₃₈N₂O₈	详情	详情
(XIX)	53179	12-(tert-butyl) 8-methyl (8S,11R,12S)-2,10-dioxo-11-(4-{[(trifluoromethyl)sulfonyl]amino}benzyl)-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxylate	n/a	C₂₇H₃₈F₃N₃O₉S	详情	详情
(XX)	53180	2-Trifluoromethylbenzeneboronic acid; 2-Trifluoromethylphenylboronic acid; o-Trifluoromethylphenylboronic acid	1423-27-4	C₇H₆BF₃O₂	详情	详情
(XXI)	53181	12-(tert-butyl) 8-methyl (8S,11R,12S)-2,10-dioxo-11-{[2'-(trifluoromethyl)[1,1'-biphenyl]-4-yl]methyl}-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxylate	n/a	C₃₃H₄₁F₃N₂O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Suzuki coupling between 2-bromo-4-formylbenzonitrile (I) and 2-(trifluoromethyl)phenylboronic acid (II) affords the biphenyl aldehyde (III). The lithiated derivative of imidazole (IV) is then added to aldehyde (III), producing carbinol (V). Alkylation of (V) with the bromomethylpyridine (VI) by using Ag2O yields ether (VII). The chlorine atom of (VII) is finally displaced with 3-hydroxypiperidine (VIII) to provide the title compound.

参考文献中间体

合成目标

【1】 Wang, G.T.; et al.; Lead optimization of imidazole-containing inhibitors of farnesyl transferase. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 130.

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)	58990	2-bromo-4-formylbenzonitrile		C₈H₄BrNO	详情	详情
(II)	53180	2-Trifluoromethylbenzeneboronic acid; 2-Trifluoromethylphenylboronic acid; o-Trifluoromethylphenylboronic acid	1423-27-4	C₇H₆BF₃O₂	详情	详情
(III)	58991	5-formyl-2'-(trifluoromethyl)[1,1'-biphenyl]-2-carbonitrile		C₁₅H₈F₃NO	详情	详情
(IV)	58992	1-methyl-2-(triethylsilyl)-1H-imidazole		C₁₀H₂₀N₂Si	详情	详情
(V)	58993	5-[hydroxy(1-methyl-1H-imidazol-5-yl)methyl]-2'-(trifluoromethyl)[1,1'-biphenyl]-2-carbonitrile		C₁₉H₁₄F₃N₃O	详情	详情
(VI)	58994	6-(bromomethyl)-2-chloronicotinonitrile		C₇H₄BrClN₂	详情	详情
(VII)	58995	2-chloro-6-{[[6-cyano-2'-(trifluoromethyl)[1,1'-biphenyl]-3-yl](1-methyl-1H-imidazol-5-yl)methoxy]methyl}nicotinonitrile		C₂₆H₁₇ClF₃N₅O	详情	详情
(VIII)	24255	3-piperidinol	6859-99-0	C₅H₁₁NO	详情	详情

Extended Information