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【结 构 式】

【分子编号】38384

【品名】3-(trifluoromethoxy)phenylamine; 3-(trifluoromethoxy)aniline

【CA登记号】1535-73-5

【 分 子 式 】C7H6F3NO

【 分 子 量 】177.1259896

【元素组成】C 47.47% H 3.41% F 32.18% N 7.91% O 9.03%

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:(V)

The reaction of N-(tert-butoxycarbonyl)-L-norleucine (I) with N,O-dimethylhydroxylamine (II) by means of EDC, HOBT and TEA in DMF gives the methoxyamide (III), which is reduced with LiAlH4 to the corresponding aldehyde (IV). The reductocondensation of (IV) with 3-(trifluoromethoxy)aniline (V) by means of NaBH(OAc)3 affords the secondary amine (VI), which is acylated with chloroacetyl chloride (VII) and NaHCO3 to the chloroacetamide (VIII). The cyclization of (VIII) by means of Cs2CO3 in DMF gives the piperazinone (IX), which is finally reductocondensed with 1-(4-cyanobenzyl)imidazole-5-carbaldehyde (X) by means of NaBH(OAc)3. The intermediate 1-(4-cyanobenzyl)imidazole-5-carbaldehyde (X) has been obtained as follows: The tritylation of 1H-imidazole-4-methanol (XI) with trityl chloride and TEA in DMF gives the corresponding 1-trityl derivative (XII), which is acetylated with Ac2O and pyridine yielding the acetate (XIII). The condensation of (XIII) with 4-(bromomethyl)benzonitrile (XIV) in hot ethyl acetate affords 4-(5-acetoxyimidazol-1-ylmethyl)benzonitrile (XV), which is hydrolyzed with LiOH in THF/water providing the carbinol (XVI). Finally, this alcohol is oxidized to the target aldehyde (X) by means of SO3 and pyridine in DMSO.

1 Bergman, J.M.; Brashear, K.; Williams, T.M.; et al.; N-Arylpiperazinone inhibitors of farnesyltransferase: Discovery and biological activity. J Med Chem 1999, 42, 19, 3779.
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) 20398 (2S)-2-[(tert-butoxycarbonyl)amino]hexanoic acid C11H21NO4 详情 详情
(II) 13361 (Methoxyamino)methane; N,O-Dimethylhydroxylamine 1117-97-1 C2H7NO 详情 详情
(III) 38382 tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]pentylcarbamate C13H26N2O4 详情 详情
(IV) 38383 tert-butyl (1S)-1-formylpentylcarbamate C11H21NO3 详情 详情
(V) 38384 3-(trifluoromethoxy)phenylamine; 3-(trifluoromethoxy)aniline 1535-73-5 C7H6F3NO 详情 详情
(VI) 38385 tert-butyl (1S)-1-[[3-(trifluoromethoxy)anilino]methyl]pentylcarbamate C18H27F3N2O3 详情 详情
(VII) 11296 2-Chloroacetyl chloride; Chloroacetic chloride 79-04-9 C2H2Cl2O 详情 详情
(VIII) 38386 tert-butyl (1S)-1-[[(2-chloroacetyl)-3-(trifluoromethoxy)anilino]methyl]pentylcarbamate C20H28ClF3N2O4 详情 详情
(IX) 38387 tert-butyl (2S)-2-butyl-5-oxo-4-[3-(trifluoromethoxy)phenyl]-1-piperazinecarboxylate C20H27F3N2O4 详情 详情
(X) 38388 4-[(5-formyl-1H-imidazol-1-yl)methyl]benzonitrile C12H9N3O 详情 详情
(XI) 38393 1H-imidazol-4-ylmethanol C4H6N2O 详情 详情
(XII) 38392 (1-trityl-1H-imidazol-4-yl)methanol C23H20N2O 详情 详情
(XIII) 38391 (1-trityl-1H-imidazol-4-yl)methyl acetate C25H22N2O2 详情 详情
(XIV) 14200 4-(Bromomethyl)benzonitrile; alpha-Bromo-p-tolunitrile 17201-43-3 C8H6BrN 详情 详情
(XV) 38390 [1-(4-cyanobenzyl)-1H-imidazol-5-yl]methyl acetate C14H13N3O2 详情 详情
(XVI) 38389 4-[[5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]benzonitrile C12H11N3O 详情 详情
Extended Information