1-(4-nitrobenzyl)-1H-1,2,4-triazole -Drug Synthesis Database

【结构式】

【分子编号】16868

【品名】1-(4-nitrobenzyl)-1H-1,2,4-triazole

【CA登记号】

【分子式】C₉H₈N₄O₂

【分子量】204.18828

【元素组成】C 52.94% H 3.95% N 27.44% O 15.67%

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：(VIII)

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2

该中间体在本合成路线中的序号：(VIII)

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

Extended Information