4-(bromomethyl)-1-fluoro-2-nitrobenzene -Drug Synthesis Database

【结构式】

【分子编号】47038

【品名】4-(bromomethyl)-1-fluoro-2-nitrobenzene

【CA登记号】

【分子式】C₇H₅BrFNO₂

【分子量】234.0246432

【元素组成】C 35.93% H 2.15% Br 34.14% F 8.12% N 5.99% O 13.67%

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：(XII)

The synthesis of intermediate (XXI) has been performed as follows: The condensation of 4-fluoro-3-nitrobenzyl bromide (XII) with the chiral dihydropyrazine (XIII) by means of BuLi and CuCN gives the chiral adduct (XIV), which is treated with TFA to yield the 4-fluoro-3-nitro-D- phenylalanine (XV). The N-protection of (XV) with Teoc-Cl gives the N-protected phenylalanine (XVI), which is condensed with the already described intermediate (XI) by means of PyBop to yield the amide (XVII). The oxidation of the primary OH group of (XVII) with DMP and NaClO2 affords the carboxylic acid (XVIII), which is cyclized to the cyclic amide (XIX). The cleavage of he protecting groups of (XIX) with HCl, followed by selective N-protection with Boc2O, provides primary carbinol (XX), which is finally oxidized with DMP and NaClO2 to give the desired carboxylic acid intermediate (XXI).

参考文献中间体

合成目标

【1】 Boger, D.L.; et al.; First and second generation total synthesis of the teicoplanin aglycon. J Am Chem Soc 2001, 123, 9, 1862.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	47037	tert-butyl (1R)-1-[3-(3-[(1S)-1-amino-2-[(2-methoxyethoxy)methoxy]ethyl]-5-methoxyphenoxy)-4-methoxyphenyl]-2-hydroxyethylcarbamate		C₂₇H₄₀N₂O₉	详情	详情
(XII)	47038	4-(bromomethyl)-1-fluoro-2-nitrobenzene		C₇H₅BrFNO₂	详情	详情
(XIII)	10296	(R)-2,5-Dihydro-3,6-dimethoxy-2-isopropylpyrazine; (3R)-3-Isopropyl-5-methoxy-3,6-dihydro-2-pyrazinyl methyl ether; (2R)-2-Isopropyl-3,6-dimethoxy-2,5-dihydropyrazine	109838-85-9	C₉H₁₆N₂O₂	详情	详情
(XIV)	47039	(2R,5S)-2-(4-fluoro-3-nitrobenzyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine; (3R,6S)-3-(4-fluoro-3-nitrobenzyl)-6-isopropyl-5-methoxy-3,6-dihydro-2-pyrazinyl methyl ether		C₁₆H₂₀FN₃O₄	详情	详情
(XV)	47040	(2R)-2-amino-3-(4-fluoro-3-nitrophenyl)propionic acid		C₉H₉FN₂O₄	详情	详情
(XVI)	47041	(2R)-3-(4-fluoro-3-nitrophenyl)-2-([[2-(trimethylsilyl)ethoxy]carbonyl]amino)propionic acid		C₁₅H₂₁FN₂O₆Si	详情	详情
(XVII)	47042	2-(trimethylsilyl)ethyl (1R,4S)-4-[3-(5-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-hydroxyethyl]-2-methoxyphenoxy)-5-methoxyphenyl]-1-(4-fluoro-3-nitrobenzyl)-2-oxo-6,8,11-trioxa-3-azadodec-1-ylcarbamate		C₄₂H₅₉FN₄O₁₄Si	详情	详情
(XVIII)	47043	(2R)-2-[(tert-butoxycarbonyl)amino]-2-[3-[3-((1S,4R)-4-(4-fluoro-3-nitrobenzyl)-1-[[(2-methoxyethoxy)methoxy]methyl]-10,10-dimethyl-3,6-dioxo-7-oxa-2,5-diaza-10-silaundec-1-yl)-5-methoxyphenoxy]-4-methoxyphenyl]ethanoic acid		C₄₂H₅₇FN₄O₁₅Si	详情	详情
(XIX)	47044	tert-butyl (8S,11R,14R)-11-(4-fluoro-3-nitrobenzyl)-5,18-dimethoxy-8-[[(2-methoxyethoxy)methoxy]methyl]-10,13-dioxo-2-oxa-9,12-diazatricyclo[13.3.1.1(3,7)]icosa-1(19),3(20),4,6,15,17-hexaen-14-ylcarbamate		C₃₆H₄₃FN₄O₁₂	详情	详情
(XX)	47045	tert-butyl (8S,11R,14R)-11-(4-fluoro-3-nitrobenzyl)-8-(hydroxymethyl)-5,18-dimethoxy-10,13-dioxo-2-oxa-9,12-diazatricyclo[13.3.1.1(3,7)]icosa-1(19),3(20),4,6,15,17-hexaen-14-ylcarbamate		C₃₂H₃₅FN₄O₁₀	详情	详情
(XXI)	47046	(8S,11R,14R)-14-[(tert-butoxycarbonyl)amino]-11-(4-fluoro-3-nitrobenzyl)-5,18-dimethoxy-10,13-dioxo-2-oxa-9,12-diazatricyclo[13.3.1.1(3,7)]icosa-1(19),3(20),4,6,15,17-hexaene-8-carboxylic acid		C₃₂H₃₃FN₄O₁₁	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Alternatively, the reduction of 4-fluoro-3-nitrobenzoic acid (I) with BH3/THF gives the benzyl alcohol (IX), which is treated with PBr3 in ethyl ether to yield the benzyl bromide (X). Finally, this compound is condensed with 1-methylpiperazine (II) by means of DIEA in THF to afford the already reported benzyl piperazine intermediate (IV).

参考文献中间体

合成目标

【1】 Heyer, D.; et al.; 2-Aminobenzimidazoles: A class of orally bioavailable and brain permeable neuropeptide YY5 antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 284.

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)	46937	4-fluoro-3-nitrobenzoic acid	453-71-4	C₇H₄FNO₄	详情	详情
(II)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情
(IV)	54042	1-(4-fluoro-3-nitrobenzyl)-4-methylpiperazine		C₁₂H₁₆FN₃O₂	详情	详情
(IX)	54046	(4-fluoro-3-nitrophenyl)methanol		C₇H₆FNO₃	详情	详情
(X)	47038	4-(bromomethyl)-1-fluoro-2-nitrobenzene		C₇H₅BrFNO₂	详情	详情

Extended Information