3-amino-1,2,4-benzotriazin-1-ium-1-olate; 3-Amino-1,2,4-benzotriazine-1-oxide -Drug Synthesis Database

【结构式】

【分子编号】11609

【品名】3-amino-1,2,4-benzotriazin-1-ium-1-olate; 3-Amino-1,2,4-benzotriazine-1-oxide

【CA登记号】5424-06-6

【分子式】C₇H₆N₄O

【分子量】162.151

【元素组成】C 51.85% H 3.73% N 34.55% O 9.87%

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：(V)

Tirapazamine can be obtained by several related ways: 1) By condensation of benzofurazan (I) with cyanamide disodium salt (II) in hot methanol/water. 2) The condensation of 2-nitroaniline (III) with cyanamide (IV) by heating at 100 C gives 3-amino-1,2,4-bezotriazine 1-oxide (V), which is then oxidized with 30% aqueous H2O2 in hot acetic acid. 3) The reaction of 3-hydroxy-1,2,4-benzotriazine 1-oxide (VI) with refluxing POCl3 and dimethylaniline gives 3-chloro-1,2,4-benzotriazine 1-oxide (VII), which by reaction with dry ammonia in ethanol is converted into the corresponding amino derivative (V), already obtained.

参考文献中间体

合成目标

【1】 Schofield, K.; Robbins, R.F.; Polyazabicyclic compounds. Part II. Further derivatives of benzo-1:2:4-triazine. J Chem Soc 1957, 3186.
【2】 Tennant, G.; Mason, J.C.; Heterocyclic N-oxides. Part VI. Synthesis and nuclear magnetic resonance spectra of 3-aminobenzo-1,2,4-triazines and their mono- and di-N-oxides. J Chem Soc B 1970, 911.
【3】 Robinson, C.; Castaner, J.; Tirapazamine. Drugs Fut 1995, 20, 3, 256.
【4】 Ley, K.; Seng, F.; Metzer, K.G. (Bayer AG); 3-Amino-1,2,4-benzotriazine-1,4-di-N-oxides and processes for their preparation. US 3868371; US 3980779; US 4001410 .

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)	11607	2,1,3-benzoxadiazole 1-oxide; 2,1,3-benzoxadiazol-1-ium-1-olate	480-96-6	C₆H₄N₂O₂	详情	详情
(II)	63311	2-chloro-1-ethoxyethyl ethyl ether; 2-chloro-1,1-diethoxyethane		C₆H₁₃ClO₂	详情	详情
(III)	11608	o-Nitroaniline; 2-Nitroaniline; 2-Nitrophenylamine	88-74-4	C₆H₆N₂O₂	详情	详情
(IV)	19648	Cyanamide	420-04-2	CH₂N₂	详情	详情
(V)	11609	3-amino-1,2,4-benzotriazin-1-ium-1-olate; 3-Amino-1,2,4-benzotriazine-1-oxide	5424-06-6	C₇H₆N₄O	详情	详情
(VI)	11610	3-hydroxy-1,2,4-benzotriazin-1-ium-1-olate		C₇H₅N₃O₂	详情	详情
(VII)	11611	3-chloro-1,2,4-benzotriazin-1-ium-1-olate		C₇H₄ClN₃O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The reaction of 2-nitroaniline (I) with cyanamide and HCl at 100 C, followed by a treatment with NaOH at the same temperature gives the benzotriazine N-oxide (II), which is diazotized with NaNO2 and HCl, followed by a treatment with POCl3 and dimethylaniline to yield the chloro derivative (III). The reaction of (III) with tetraethyltin and Pd(PPh3)4 in hot DME affords the ethyl derivative (IV), which is finally oxidized with trifluoroperacetic acid in dichloromethane to provide the target N1, N4-bis oxide compound.

参考文献中间体

合成目标

【1】 Hay, M.P.; Denny, W.A.; New and versatile syntheses of 3-alkyl- and 3-aryl-1,2,4-benzotriazine 1,4-dioxides: Preparation of the bioreductive cytotoxins SR 4895 and SR 4941. Tetrahedron Lett 2002, 43, 52, 9569.

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)	11608	o-Nitroaniline; 2-Nitroaniline; 2-Nitrophenylamine	88-74-4	C₆H₆N₂O₂	详情	详情
(II)	11609	3-amino-1,2,4-benzotriazin-1-ium-1-olate; 3-Amino-1,2,4-benzotriazine-1-oxide	5424-06-6	C₇H₆N₄O	详情	详情
(III)	11611	3-chloro-1,2,4-benzotriazin-1-ium-1-olate		C₇H₄ClN₃O	详情	详情
(IV)	62231	3-ethyl-1,2,4-benzotriazin-1-ium-1-olate		C₉H₉N₃O	详情	详情

Extended Information