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【结 构 式】

【分子编号】68914

【品名】(E)-4-cyclopropyl-N-hydroxy-1-naphthimidoyl bromide

【CA登记号】 

【 分 子 式 】C14H12BrNO

【 分 子 量 】290.15942

【元素组成】C 57.95% H 4.17% Br 27.54% N 4.83% O 5.51%

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:(XIV)

Oxidation of (4-cyclopropyl-1-naphthyl)methanol (XI) by means of MnO2 in CH2Cl2 yields 4-cyclopropyl-1-naphthaldehyde (XII), which is then treated with NH2OH·HCl or (NH2OH)2SO4 in the presence of NaOMe (generated from Na in MeOH) to give 4-cyclopropyl-1-naphthaldehyde oxime (XIII). Bromination of oxime (XIII) with NBS in acetonitrile provides the corresponding oximidoyl bromide (XIV), which is finally treated with CS(NH2)2 in the presence of Et3N in THF (I) .
Chlorination of oxime (XIII) using 1,3-dichloro-5,5-dimethylhydantoin (DDH) or trichloroisocyanuric acid (TCCA) in acetonitrile affords 4-cyclopropyl-N-hydroxynaphthalene-1-carboximidoyl chloride (XV), which is then treated with CS(NH2)2 or CH3CSNH2 in the presence of Et3N in THF .
Coupling of 1-bromonaphthalene (XVI) with cyclopropylmagnesium bromide (XVII) in the presence of NiCl2(dppp) in THF gives 1-cyclopropylnaphthalene (XVIII), which is then nitrated with NaNO2 at 0 °C to produce 1-cyclopropyl-4-nitronaphthalene (XIX). Reduction of the nitronaphthalene derivative (XIX) by means of H2 over Pd/C in EtOH yields 4-cyclopropyl-1-naphthylamine (XX), which is finally treated with CSCl2 and DIEA in CH2Cl2 at 0 °C .

1 Miner, J., Quart, B.D., Girardet, J.-L. (Ardea Biosciences, Inc.). Treatment of gout. WO 201116852.
2 Quart, B.D., Girardet, J.-L., Gunic, E., Yeh, L.-T. (Ardea Biosciences, Inc.).Novel compounds and composition and methods of use. CA 2706858, CN 01918377, EP 2217577, JP 2011504935, KR 2010085195, US 2009197825, US 2011268801, WO 009070740.
3 Zamansky, I., Galvin, G., Girardet, J.-L. (Ardea Biosciences, Inc.). Polymorphic, crystalline and mesophase forms of sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate, and uses thereof. WO 2011085009.
4 Liu, X., Hong, D., Wu, X. (Taizhou Hwasun Pharm. & Chem. Co., Ltd.). Method for preparing 4-cyclopropyl-1-isothiocyanonaphthalene and intermediate 4-cyclopropyl-1-naphthaldehyde oxime/halide. CN 102040546.
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) 68901 4-cyclopropyl-1-naphthyl isothiocyanate 878671-95-5 C14H11NS 详情 详情
(XI) 68910 (4-cyclopropyl-1-naphthyl)methanol   C14H14O 详情 详情
(XII) 68911 4-cyclopropyl-1-naphthaldehyde   C14H12O 详情 详情
(XIII) 68912 (Z)-4-cyclopropyl-1-naphthaldehyde oxime;4-cyclopropyl-1-naphthaldehyde oxime   C14H13NO 详情 详情
(XIV) 68914 (E)-4-cyclopropyl-N-hydroxy-1-naphthimidoyl bromide   C14H12BrNO 详情 详情
(XV) 68913 4-cyclopropyl-N-hydroxynaphthalene-1-carboximidoyl chloride;(E)-4-cyclopropyl-N-hydroxy-1-naphthimidoyl chloride   C14H12ClNO 详情 详情
(XVI) 10105 1-Bromonaphthalene 90-11-9 C10H7Br 详情 详情
(XVII) 12450 Bromo(cyclopropyl)magnesium;cyclopropylmagnesium bromide;cyclopropylmagnesiumbromide 23719-80-4 C3H5BrMg 详情 详情
(XVIII) 68915 1-cyclopropylnaphthalene 25033-19-6 C13H12 详情 详情
(XIX) 68916 1-cyclopropyl-4-nitronaphthalene   C13H11NO2 详情 详情
(XX) 68917 4-cyclopropyl-1-naphthylamine 878671-94-4 C13H13N 详情 详情
Extended Information