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【结 构 式】

【分子编号】18412

【品名】(2S)-4-(2,4-difluorophenyl)-4-oxo-2-[(2,2,2-trifluoroacetyl)amino]butyric acid

【CA登记号】

【 分 子 式 】C12H8F5NO4

【 分 子 量 】325.191876

【元素组成】C 44.32% H 2.48% F 29.21% N 4.31% O 19.68%

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:(IV)

Reaction of L-aspartic acid (I) with trifluoroacetic acid and trifluoroacetic anhydride afforded N-trifluoroacetyl-L-aspartic anhydride (II). Then, Friedel-Crafts acylation of 1,3-difluorobenzene (III) with this anhydride in the presence of AlCl3 gave ketone (IV). The reduction of the carbonyl group of (IV) was effected by catalytic hydrogenation in the presence of Pearlman's catalyst, and the resulting phenylbutyric acid (V) was converted to acid chloride on treatment with PCl5 in cold dichloromethane, and subsequently cyclized by addition of AlCl3 to yield tetralone (VI). Hydrogenolysis of (VI) in the presence of Pearlman's catalyst gave tetrahydronaphthalene (VII), and further hydrolysis of trifluoroacetamide with LiOH yielded (S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl amine (VIII). Imidazole ring was then constructed by treatment of this amine with 1,3-dihydroxyacetone (IX) and potassium thiocyanate in acidic medium, and the hydroxyl group of the resulting X was substituted by a formamido group by either heating in formamide at 175 C or with ammonium formate. Finally, formamide (XI) was hydrolyzed in refluxing isopropanolic HCl.

1 Martinez, G.R.; Repke, D.B.; Teitelbaum, P.J.; Walker, K.A.M.; Gooding, O.W.; Whiting, R.L.; Bansal, R.P.; Muehldorf, A.V. (Syntex (USA), Inc.); Benzocycloalkylazolethione derivs.. JP 1997512269; US 5438150; WO 9529165 .
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) 13070 L-Aspartic acid; (2S)-2-Aminobutanedioic acid 56-84-8 C4H7NO4 详情 详情
(II) 18410 N-[(3S)-2,5-dioxotetrahydro-3-furanyl]-2,2,2-trifluoroacetamide 777-33-3 C6H4F3NO4 详情 详情
(III) 13095 m-Difluorobenzene; 1,3-Difluorobenzene 372-18-9 C6H4F2 详情 详情
(IV) 18412 (2S)-4-(2,4-difluorophenyl)-4-oxo-2-[(2,2,2-trifluoroacetyl)amino]butyric acid C12H8F5NO4 详情 详情
(V) 18413 (2S)-4-(2,4-difluorophenyl)-2-[(2,2,2-trifluoroacetyl)amino]butyric acid C12H10F5NO3 详情 详情
(VI) 18414 N-[(2S)-5,7-difluoro-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl]-2,2,2-trifluoroacetamide C12H8F5NO2 详情 详情
(VII) 18415 N-[(2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenyl]-2,2,2-trifluoroacetamide C12H10F5NO 详情 详情
(VIII) 18416 (2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenylamine; (2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenamine C10H11F2N 详情 详情
(IX) 14575 Dihydroxyacetone; 1,3-dihydroxyacetone 96-26-4 C3H6O3 详情 详情
(X) 18418 1-[(2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenyl]-5-(hydroxymethyl)-1,3-dihydro-2H-imidazole-2-thione C14H14F2N2OS 详情 详情
(XI) 18419 [3-[(2S)-5,7-difluoro-1,2,3,4-tetrahydro-2-naphthalenyl]-2-thioxo-2,3-dihydro-1H-imidazol-4-yl]methylformamide C15H15F2N3OS 详情 详情
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