合成路线:Reduction of 2-methyl-2-nitropropane (I) with either zinc and acetic acid or aluminum and HgCl2 afforded the corresponding hydroxylamine (II).Subsequent condensation of (II) with aldehyde (III) furnished the title nitrone.
合成路线:NXY-059 is synthesized by condensation of N-tert-butylhydroxylamine (I) or its acetate or hydrochloride salts and disodium benzaldehyde-2,4-disulfonate (II) directly in refluxing MeOH or mixtures of MeOH/water or i-PrOH/MeOH/water or by means of MeONa in refluxing MeOH/water or i-PrOH/MeOH/water.N-tert-butylhydroxylamine (I) can be prepared as follows: a) Reduction of 2-methyl-2-nitropropane (III) with either Zn in HOAc/EtOH or aluminum foil and HgCl2 in EtOH/ether/H2O.b) Condensation of benzaldehyde (IV) with tert-butyl-amine (V) in refluxing toluene provides N-benzylidene-N-tert-butylamine (VI),which is oxidized with meta-chloroperbenzoic acid and Na2CO3 in water/toluene/ EtOH to furnish the phenyloxaziridine derivative (VII).Finally,the oxaziridine ring of (VII) is opened by treatment with H2SO4/HOAc in EtOH/H2O.c) Heating of the phenyloxaziridine derivative (VII) at 130 C gives N-tert-butylphenylnitrone (VIII),which is finally treated with H2SO4/HOAc in toluene.Disodium benzaldehyde-2,4-disulfonate (II) can be obtained as follows: a) Heating of 2,4-dichlorobenzaldehyde (IX) with sodium sulfite at 170 癈 in water,followed by oxidation with sodium hypochlorite.b) Reaction of 2,4-dichlorobenzal chloride (X) with sodium sulfite and Na2CO3 or NaHCO3 at 170 C in water,followed by oxidation with sodium hypochlorite.
参考文献标题:2,4-Disulfonyl phenyl butyl nitrone,its salts,and their use as pharmaceuticals
文献作者:Carney,J.M.(Oklahoma Medical Research Foundation; University of Kentucky)
参考来源:WO 9517876
合成路线:NXY-059 is synthesized by condensation of N-tert-butylhydroxylamine (I) or its acetate or hydrochloride salts and disodium benzaldehyde-2,4-disulfonate (II) directly in refluxing MeOH or mixtures of MeOH/water or i-PrOH/MeOH/water or by means of MeONa in refluxing MeOH/water or i-PrOH/MeOH/water.N-tert-butylhydroxylamine (I) can be prepared as follows: a) Reduction of 2-methyl-2-nitropropane (III) with either Zn in HOAc/EtOH or aluminum foil and HgCl2 in EtOH/ether/H2O.b) Condensation of benzaldehyde (IV) with tert-butyl-amine (V) in refluxing toluene provides N-benzylidene-N-tert-butylamine (VI),which is oxidized with meta-chloroperbenzoic acid and Na2CO3 in water/toluene/ EtOH to furnish the phenyloxaziridine derivative (VII).Finally,the oxaziridine ring of (VII) is opened by treatment with H2SO4/HOAc in EtOH/H2O.c) Heating of the phenyloxaziridine derivative (VII) at 130 C gives N-tert-butylphenylnitrone (VIII),which is finally treated with H2SO4/HOAc in toluene.Disodium benzaldehyde-2,4-disulfonate (II) can be obtained as follows: a) Heating of 2,4-dichlorobenzaldehyde (IX) with sodium sulfite at 170 癈 in water,followed by oxidation with sodium hypochlorite.b) Reaction of 2,4-dichlorobenzal chloride (X) with sodium sulfite and Na2CO3 or NaHCO3 at 170 C in water,followed by oxidation with sodium hypochlorite.
参考文献标题:Novel process for the preparation of alpha-(2,4-disulfophenyl)-N-tert-butylnitrone and pharmaceutically acceptable salts thereof
文献作者:Kruk,H.; McGinley,J.; Pouhov,S.; Blixt,J.; Vajda,J.(AstraZeneca AB; Centaur Pharmaceuticals,Inc.)
参考来源:WO 0151460
合成路线:NXY-059 is synthesized by condensation of N-tert-butylhydroxylamine (I) or its acetate or hydrochloride salts and disodium benzaldehyde-2,4-disulfonate (II) directly in refluxing MeOH or mixtures of MeOH/water or i-PrOH/MeOH/water or by means of MeONa in refluxing MeOH/water or i-PrOH/MeOH/water.N-tert-butylhydroxylamine (I) can be prepared as follows: a) Reduction of 2-methyl-2-nitropropane (III) with either Zn in HOAc/EtOH or aluminum foil and HgCl2 in EtOH/ether/H2O.b) Condensation of benzaldehyde (IV) with tert-butyl-amine (V) in refluxing toluene provides N-benzylidene-N-tert-butylamine (VI),which is oxidized with meta-chloroperbenzoic acid and Na2CO3 in water/toluene/ EtOH to furnish the phenyloxaziridine derivative (VII).Finally,the oxaziridine ring of (VII) is opened by treatment with H2SO4/HOAc in EtOH/H2O.c) Heating of the phenyloxaziridine derivative (VII) at 130 C gives N-tert-butylphenylnitrone (VIII),which is finally treated with H2SO4/HOAc in toluene.Disodium benzaldehyde-2,4-disulfonate (II) can be obtained as follows: a) Heating of 2,4-dichlorobenzaldehyde (IX) with sodium sulfite at 170 癈 in water,followed by oxidation with sodium hypochlorite.b) Reaction of 2,4-dichlorobenzal chloride (X) with sodium sulfite and Na2CO3 or NaHCO3 at 170 C in water,followed by oxidation with sodium hypochlorite.
参考文献标题:Novel process for the preparation of alpha-(2,4-disulfophenyl)-N-tert-butylnitrone and pharmaceutically acceptable salts thereof
文献作者:Wilcox,A.; Blixt,J.; Kruk,H.; Larsson,U.; McGinley,J.; Pouhov,S.; Vajda,J.(AstraZeneca AB; Centaur Pharmaceuticals,Inc.)
参考来源:WO 0151461
合成路线:NXY-059 is synthesized by condensation of N-tert-butylhydroxylamine (I) or its acetate or hydrochloride salts and disodium benzaldehyde-2,4-disulfonate (II) directly in refluxing MeOH or mixtures of MeOH/water or i-PrOH/MeOH/water or by means of MeONa in refluxing MeOH/water or i-PrOH/MeOH/water.N-tert-butylhydroxylamine (I) can be prepared as follows: a) Reduction of 2-methyl-2-nitropropane (III) with either Zn in HOAc/EtOH or aluminum foil and HgCl2 in EtOH/ether/H2O.b) Condensation of benzaldehyde (IV) with tert-butyl-amine (V) in refluxing toluene provides N-benzylidene-N-tert-butylamine (VI),which is oxidized with meta-chloroperbenzoic acid and Na2CO3 in water/toluene/ EtOH to furnish the phenyloxaziridine derivative (VII).Finally,the oxaziridine ring of (VII) is opened by treatment with H2SO4/HOAc in EtOH/H2O.c) Heating of the phenyloxaziridine derivative (VII) at 130 C gives N-tert-butylphenylnitrone (VIII),which is finally treated with H2SO4/HOAc in toluene.Disodium benzaldehyde-2,4-disulfonate (II) can be obtained as follows: a) Heating of 2,4-dichlorobenzaldehyde (IX) with sodium sulfite at 170 癈 in water,followed by oxidation with sodium hypochlorite.b) Reaction of 2,4-dichlorobenzal chloride (X) with sodium sulfite and Na2CO3 or NaHCO3 at 170 C in water,followed by oxidation with sodium hypochlorite.
参考文献标题:Novel salts of N-tert-butylhydroxylamine
文献作者:Blixt,J.(AstraZeneca AB)
参考来源:WO 0002848
合成路线:NXY-059 is synthesized by condensation of N-tert-butylhydroxylamine (I) or its acetate or hydrochloride salts and disodium benzaldehyde-2,4-disulfonate (II) directly in refluxing MeOH or mixtures of MeOH/water or i-PrOH/MeOH/water or by means of MeONa in refluxing MeOH/water or i-PrOH/MeOH/water.N-tert-butylhydroxylamine (I) can be prepared as follows: a) Reduction of 2-methyl-2-nitropropane (III) with either Zn in HOAc/EtOH or aluminum foil and HgCl2 in EtOH/ether/H2O.b) Condensation of benzaldehyde (IV) with tert-butyl-amine (V) in refluxing toluene provides N-benzylidene-N-tert-butylamine (VI),which is oxidized with meta-chloroperbenzoic acid and Na2CO3 in water/toluene/ EtOH to furnish the phenyloxaziridine derivative (VII).Finally,the oxaziridine ring of (VII) is opened by treatment with H2SO4/HOAc in EtOH/H2O.c) Heating of the phenyloxaziridine derivative (VII) at 130 C gives N-tert-butylphenylnitrone (VIII),which is finally treated with H2SO4/HOAc in toluene.Disodium benzaldehyde-2,4-disulfonate (II) can be obtained as follows: a) Heating of 2,4-dichlorobenzaldehyde (IX) with sodium sulfite at 170 癈 in water,followed by oxidation with sodium hypochlorite.b) Reaction of 2,4-dichlorobenzal chloride (X) with sodium sulfite and Na2CO3 or NaHCO3 at 170 C in water,followed by oxidation with sodium hypochlorite.
参考文献标题:Process for the preparation of alkali metal and alkaline earth salts of benzaldehyde-2,4-di-sulfonic acid
文献作者:Metz,H.J.(Aventis Pharma AG)
参考来源:DE 3434079; US 4710322
合成路线:NXY-059 is synthesized by condensation of N-tert-butylhydroxylamine (I) or its acetate or hydrochloride salts and disodium benzaldehyde-2,4-disulfonate (II) directly in refluxing MeOH or mixtures of MeOH/water or i-PrOH/MeOH/water or by means of MeONa in refluxing MeOH/water or i-PrOH/MeOH/water.N-tert-butylhydroxylamine (I) can be prepared as follows: a) Reduction of 2-methyl-2-nitropropane (III) with either Zn in HOAc/EtOH or aluminum foil and HgCl2 in EtOH/ether/H2O.b) Condensation of benzaldehyde (IV) with tert-butyl-amine (V) in refluxing toluene provides N-benzylidene-N-tert-butylamine (VI),which is oxidized with meta-chloroperbenzoic acid and Na2CO3 in water/toluene/ EtOH to furnish the phenyloxaziridine derivative (VII).Finally,the oxaziridine ring of (VII) is opened by treatment with H2SO4/HOAc in EtOH/H2O.c) Heating of the phenyloxaziridine derivative (VII) at 130 C gives N-tert-butylphenylnitrone (VIII),which is finally treated with H2SO4/HOAc in toluene.Disodium benzaldehyde-2,4-disulfonate (II) can be obtained as follows: a) Heating of 2,4-dichlorobenzaldehyde (IX) with sodium sulfite at 170 癈 in water,followed by oxidation with sodium hypochlorite.b) Reaction of 2,4-dichlorobenzal chloride (X) with sodium sulfite and Na2CO3 or NaHCO3 at 170 C in water,followed by oxidation with sodium hypochlorite.
参考文献标题:Process for the preparation of alkali metal and alkaline earth salts of benzaldehyde-2,4-disulfonic acid
文献作者:Metz,H.J.(Aventis Pharma AG)
参考来源:DE 3434038; US 4715995
产品链接: CAS No. 168021-79-2››