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【结 构 式】

【分子编号】52179

【品名】2,4-dichloro-1-(dichloromethyl)benzene

【CA登记号】

【 分 子 式 】C7H4Cl4

【 分 子 量 】229.91956

【元素组成】C 36.57% H 1.75% Cl 61.68%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(X)

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 °C in water 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.

1 Leeson, P.A.; del Fresno, M.; Castañer, J.; Sorbera, L.A.; NXY-059. Drugs Fut 2002, 27, 3, 240.
2 Carney, J.M. (Oklahoma Medical Research Foundation; University of Kentucky); 2,4-Disulfo phenyl butyl nitrone, its salts and their use as pharmaceuticals. US 5780510 .
3 Carney, J.M. (Oklahoma Medical Research Foundation; University of Kentucky); 2,4-Disulfonyl phenyl butyl nitrone, its salts, and their use as pharmaceuticals. WO 9517876 .
4 Metz, H.J. (Aventis Pharma AG); Process for the preparation of alkali metal and alkaline earth salts of benzaldehyde-2,4-disulfonic acid. DE 3434038; US 4715995 .
5 Metz, H.J. (Aventis Pharma AG); Process for the preparation of alkali metal and alkaline earth salts of benzaldehyde-2,4-di-sulfonic acid. DE 3434079; US 4710322 .
6 Blixt, J. (AstraZeneca AB); Novel salts of N-tert-butylhydroxylamine. WO 0002848 .
7 Kruk, H.; McGinley, J.; Pouhov, S.; Blixt, J.; Vajda, J. (AstraZeneca AB; Centaur Pharmaceuticals, Inc.); Novel process for the preparation of alpha-(2,4-disulfophenyl)-N-tert-butylnitrone and pharmaceutically acceptable salts thereof. WO 0151460 .
8 Wilcox, A.; Blixt, J.; Kruk, H.; Larsson, U.; McGinley, J.; Pouhov, S.; Vajda, J. (AstraZeneca AB; Centaur Pharmaceuticals, Inc.); Novel process for the preparation of alpha-(2,4-disulfophenyl)-N-tert-butylnitrone and pharmaceutically acceptable salts thereof. WO 0151461 .
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) 35455 N-(tert-butyl)hydroxylamine; 2-(hydroxyamino)-2-methylpropane C4H11NO 详情 详情
(II) 37311 Benzaldehyde-2,4-disulfonic acid disodium; disodium 4-formyl-1,3-benzenedisulfonate 33513-44-9 C7H4Na2O7S2 详情 详情
(III) 37310 2-methyl-2-nitropropane 594-70-7 C4H9NO2 详情 详情
(IV) 10498 Benzaldehyde;Benzoic aldehyde;Phenylmethanal 100-52-7 C7H6O 详情 详情
(V) 17895 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine 75-64-9 C4H11N 详情 详情
(VI) 52176 N-(tert-butyl)-N-[(Z)-benzylidene]amine; 2-methyl-N-[(Z)-benzylidene]-2-propanamine C11H15N 详情 详情
(VII) 52177 2-(tert-butyl)-3-phenyl-1,2-oxaziridine C11H15NO 详情 详情
(VIII) 52178 tert-butyl[(Z)-benzylidene]ammoniumolate C11H15NO 详情 详情
(IX) 22196 2,4-dichlorobenzaldehyde 874-42-0 C7H4Cl2O 详情 详情
(X) 52179 2,4-dichloro-1-(dichloromethyl)benzene C7H4Cl4 详情 详情
Extended Information