1-(Bromomethyl)-4-nitrobenzene; para-Nitrobenzyl bromide -Drug Synthesis Database

【结构式】

【分子编号】16866

【品名】1-(Bromomethyl)-4-nitrobenzene; para-Nitrobenzyl bromide

【CA登记号】100-11-8

【分子式】C₇H₆BrNO₂

【分子量】216.03418

【元素组成】C 38.92% H 2.8% Br 36.99% N 6.48% O 14.81%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(XLII)

5) The esterification of olivanic acid MM-17880 (XLI) with 4-nitrobenzyl chloride (XLII) gives the corresponding ester (XLIII), which is ethoxylated with triethyloxonium tetrafluoroborate yielding the ethyl sulfate (XLIV). Elimination of sulfuric acid affords the ethylidene derivative (XLV), which is finally reduced to PS-5 4-nitrobenzyl ester (XV) by means of NaBH4.

参考文献中间体

合成目标

【1】 Corbett, D.F.; Eglington, A.J.; Conversion of the olivanic acids into antibiotics of the PS-5 type: Use of a new carboxy protecting group. J Chem Soc Chem Commun 1980, 1083-4.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	20035	4-nitrobenzyl (5R,6R)-3-[[2-(acetamido)ethyl]sulfanyl]-6-ethyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₀H₂₃N₃O₆S	详情	详情
(XLI)	20061	3-[[2-(acetamido)ethyl]sulfanyl]-7-oxo-6-[1-(sulfooxy)ethyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid		C₁₃H₁₈N₂O₈S₂	详情	详情
(XLII)	16866	1-(Bromomethyl)-4-nitrobenzene; para-Nitrobenzyl bromide	100-11-8	C₇H₆BrNO₂	详情	详情
(XLIII)	20063	4-nitrobenzyl 3-[[2-(acetamido)ethyl]sulfanyl]-7-oxo-6-[1-(sulfooxy)ethyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₀H₂₃N₃O₁₀S₂	详情	详情
(XLIV)	20064	4-nitrobenzyl (5R)-3-[[2-(acetamido)ethyl]sulfanyl]-6-[1-[(ethoxysulfonyl)oxy]ethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₂H₂₇N₃O₁₀S₂	详情	详情
(XLV)	20065	4-nitrobenzyl (5R)-3-[[2-(acetamido)ethyl]sulfanyl]-6-[(E)ethylidene]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₀H₂₁N₃O₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

2) The condensation of 4-nitrobenzyl bromide (VI) with 1,2,4-triazole sodium salt (VII) in DMF gives 1-(4-nitrobenzyl)-1,2,4-triazole (VIII), which is reduced with H2 over Pd/C in ethanol/ethyl acetate yielding the aniline (I). The diazotization of (I) with NaNO2/HCl followed by reduction with SnCl2 affords the corresponding hydrazine (IX), which is cyclized with 4-chlorobutanal dimethylacetal (X) by means of HCl in refluxing ethanol/water to afford 2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl] ethylamine (XI). Finally, this amine is methylated with formaldehyde, sodium cyanoborohydride and acetic acid in methanol.

参考文献中间体

合成目标

【1】 Castañer, J.; Mealy, N.; Rabassseda, X.; MK-0462. Drugs Fut 1995, 20, 7, 676.
【2】 Baker, R.; Matassa, V.G.; Street, L.J. (Merck Sharp & Dohme Ltd.); Imidazole, triazole and tetrazole derivs. EP 0497512; EP 0778275; US 5298520; US 5451588; US 5602162; US 5602163 .

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)	16860	4-(1H-1,2,4-triazol-1-ylmethyl)aniline; 4-(1H-1,2,4-triazol-1-ylmethyl)phenylamine		C₉H₁₀N₄	详情	详情
(VI)	16866	1-(Bromomethyl)-4-nitrobenzene; para-Nitrobenzyl bromide	100-11-8	C₇H₆BrNO₂	详情	详情
(VII)	13104	1,2,4-Triazole, sodium derivative	41253-21-8	C₂H₂N₃Na	详情	详情
(VIII)	16868	1-(4-nitrobenzyl)-1H-1,2,4-triazole		C₉H₈N₄O₂	详情	详情
(IX)	16869	1-(4-hydrazinobenzyl)-1H-1,2,4-triazole		C₉H₁₁N₅	详情	详情
(X)	16870	4-Chlorobutyraldehyde dimethylacetal; 4-Chloro-1-methoxybutyl methyl ether; 4-Chloro-1,1-dimethoxybutane		C₆H₁₃ClO₂	详情	详情
(XI)	16871	2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine; 2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]-1-ethanamine		C₁₃H₁₅N₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

3) The condensation of 4-nitrobenzyl bromide (VI) with 4-amino-1,2,4-triazole (XII) in refluxing isopropanol gives 4-amino-1-(3-nitrobenzyl)-1,2,4-triazolium bromide (XIII), which is deaminated with NaNO2/HCl to afford 1-(4-nitrobenzyl)-1,2,4-triazole (VIII). The reduction of (VIII) yields amine (I), which by diazotation and reduction with Na2SO3 yields the corresponding hydrazine (IX). Finally, (IX) is cyclized with 4-(dimethylamino)butanal dimethylacetal (XIV) in acidic water.

参考文献中间体

合成目标

【1】 Castañer, J.; Mealy, N.; Rabassseda, X.; MK-0462. Drugs Fut 1995, 20, 7, 676.
【2】 Baker, R.; Pitt, K.G.; Matassa, V.G.; Storey, D.E.; Olive, C.; Street, L.J. (Merck Sharp & Dohme Ltd.); The sulphate salt of a substd. triazole, pharmaceutical compsns. thereof, and their use in therapy. EP 0573221; US 5527817; WO 9325547 .

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)	16680	methyl (2S)-2-(acetylsulfanyl)propanoate		C₆H₁₀O₃S	详情	详情
(VI)	16866	1-(Bromomethyl)-4-nitrobenzene; para-Nitrobenzyl bromide	100-11-8	C₇H₆BrNO₂	详情	详情
(VIII)	16868	1-(4-nitrobenzyl)-1H-1,2,4-triazole		C₉H₈N₄O₂	详情	详情
(XI)	16869	1-(4-hydrazinobenzyl)-1H-1,2,4-triazole		C₉H₁₁N₅	详情	详情
(XII)	16106	4H-1,2,4-triazol-4-amine; 4-Amino-4H-1,2,4-triazole; 4H-1,2,4-triazol-4-ylamine; 4-Amino-1,2,4-triazole	584-13-4	C₂H₄N₄	详情	详情
(XIII)	16873	4-amino-1-(4-nitrobenzyl)-1H-1,2,4-triazol-4-ium bromide	6085-99-0	C₉H₁₀BrN₅O₂	详情	详情
(XIV)	16874	N-(4,4-dimethoxybutyl)-N,N-diethylamine; N,N-diethyl-4,4-dimethoxy-1-butanamine		C₁₀H₂₃NO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

The reductocondensation of tetrahydropyran-4-one (I) with methylamine (II) by means of H2 over Pd/C in methanol gives 4-(methylamino)tetrahydropyran (III), which is then alkylated with 4-nitrobenzyl bromide (IV) and K2CO3 in DMF to yield the tertiary amine (V). Finally, the nitro group of (V) is educed with SnCl2 and conc. aq. HCl to afford N-(4-aminobenzyl)-N-methyl-N-(tetrahydropyran-4-yl)amine, the target intermediate (VI).

参考文献中间体

合成目标

【1】 Hashimoto, H.; et al.; Process development of 4-[N-methyl-N-(tetrahydropyran-4-yl)aminomethyl]aniline dihydrochloride: A key intermediate for TAK-779, a small-molecule nonpeptide CCR5 antagonist. Org Process Res Dev 2002, 6, 1, 70.

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)	31563	tetrahydro-4H-pyran-4-one	29943-42-8	C₅H₈O₂	详情	详情
(II)	11021	Methanamine; Methylamine	74-89-5	CH₅N	详情	详情
(III)	55002	N-methyl-N-tetrahydro-2H-pyran-4-ylamine; N-methyltetrahydro-2H-pyran-4-amine		C₆H₁₃NO	详情	详情
(IV)	16866	1-(Bromomethyl)-4-nitrobenzene; para-Nitrobenzyl bromide	100-11-8	C₇H₆BrNO₂	详情	详情
(V)	31565	N-methyl-N-(4-nitrobenzyl)tetrahydro-2H-pyran-4-amine; N-methyl-N-(4-nitrobenzyl)-N-tetrahydro-2H-pyran-4-ylamine		C₁₃H₁₈N₂O₃	详情	详情
(VI)	31566	N-(4-aminobenzyl)-N-methyltetrahydro-2H-pyran-4-amine; N-(4-aminobenzyl)-N-methyl-N-tetrahydro-2H-pyran-4-ylamine		C₁₃H₂₀N₂O	详情	详情

Extended Information