【结 构 式】 |
【分子编号】37310 【品名】2-methyl-2-nitropropane 【CA登记号】594-70-7 |
【 分 子 式 】C4H9NO2 【 分 子 量 】103.121 【元素组成】C 46.59% H 8.8% N 13.58% O 31.03% |
合成路线1
该中间体在本合成路线中的序号:(I)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.
【1】 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 . |
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) | 37310 | 2-methyl-2-nitropropane | 594-70-7 | C4H9NO2 | 详情 | 详情 |
(II) | 35455 | N-(tert-butyl)hydroxylamine; 2-(hydroxyamino)-2-methylpropane | C4H11NO | 详情 | 详情 | |
(III) | 37311 | Benzaldehyde-2,4-disulfonic acid disodium; disodium 4-formyl-1,3-benzenedisulfonate | 33513-44-9 | C7H4Na2O7S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(III)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 |