• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】26991

【品名】1,3,5-tribromobenzene

【CA登记号】626-39-1

【 分 子 式 】C6H3Br3

【 分 子 量 】314.80182

【元素组成】C 22.89% H 0.96% Br 76.15%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(I)

The reaction of 1,3,5-tribromobenzene (I) with 4-fluorobenzaldehyde (II) by means of BuLi in ethyl ether gives the benzhydrol (III), which is condensed with ethyl acrylate (IV) by means of palladium acetate and tri o-tolylphosphine in refluxing acetonitrile yielding the phenylenebisacrylate (V). The acetylation of (V) with acetic anhydride and DMAP in dichloromethane affords the acetate (VI), which is hydrogenated with H2 over Pd/C in ethyl acetate providing the bispropanoate (VII). Selective hydrolysis of (VII) with NaOH in ethanol gives the monoacid (VIII), which is treated with oxalyl chloride in dichloromethane yielding the monoacyl chloride (IX). The reaction of (IX) with NH4OH affords the corresponding amide (X), which is treated with NaOCl and NaOH to perform degradation of the amide group and simultaneous hydrolysis of the ester group providing the amino acid (XI). Finally, this compound is sulfonated with 4-chlorophenylsulfonyl chloride (XII) and NaOH.

1 Dack, K.N.; Dickinson, R.P.; Long, C.J.; Steele, J.; Thromboxane modulating agents. 4. Design and synthesis of 3-(2-[((4-chlorophenyl)sulfonyl)amino]ethyl)benzenepropanoic acid derivatives as potent thromboxane receptor antagonists. Bioorg Med Chem Lett 1998, 8, 16, 2061.
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) 26991 1,3,5-tribromobenzene 626-39-1 C6H3Br3 详情 详情
(II) 12337 4-fluorobenzaldehyde 459-57-4 C7H5FO 详情 详情
(III) 26992 (3,5-dibromophenyl)(4-fluorophenyl)methanol C13H9Br2FO 详情 详情
(IV) 10164 ethyl acrylate 140-88-5 C5H8O2 详情 详情
(V) 26993 ethyl (E)-3-[3-[(E)-3-ethoxy-3-oxo-1-propenyl]-5-[(4-fluorophenyl)(hydroxy)methyl]phenyl]-2-propenoate C23H23FO5 详情 详情
(VI) 26994 ethyl (E)-3-[3-[(acetoxy)(4-fluorophenyl)methyl]-5-[(E)-3-ethoxy-3-oxo-1-propenyl]phenyl]-2-propenoate C25H25FO6 详情 详情
(VII) 26995 ethyl 3-[3-(3-ethoxy-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propanoate C23H27FO4 详情 详情
(VIII) 26996 3-[3-(3-ethoxy-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propionic acid C21H23FO4 详情 详情
(IX) 26997 ethyl 3-[3-(3-chloro-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propanoate C21H22ClFO3 详情 详情
(X) 26998 ethyl 3-[3-(3-amino-3-oxopropyl)-5-(4-fluorobenzyl)phenyl]propanoate C21H24FNO3 详情 详情
(XI) 26999 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propionic acid C18H20FNO2 详情 详情
(XII) 15787 4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride 98-60-2 C6H4Cl2O2S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VII)

The condensation of 1,3,5-tribromobenzene (VII) with benzaldehyde (VIII) by means of BuLi in ethyl ether gives 3,5-dibromodiphenylmethanol (IX), which is reduced with Tes-H and BF3/Et2O to yield 3,5-dibromodiphenylmethane (X). The carbonylation of (X) with BuLi and DMF in THF affords the benzaldehyde (XI), which is reduced by means of NaBH4 in methanol to provide the benzyl alcohol (XII). The reaction of (XII) with CBr4 and PPh3 in dichloromethane gives the bromomethyl derivative (XIII), which is condensed with 1,3-propanesultam (XIV) by means of K2CO3 in refluxing acetonitrile to yield the adduct (XV). The reaction of (XV) with thalium acetate and palladium acetate in DMF affords the acetyl derivative (XVI), which is brominated with Br2 and AlCl3 in dioxane to provide the bromoacetyl compound (XVII). The condensation of (XVII) with the intermediate amine (VI) by means of TEA in acetonitrile gives the secondary amine (XVIII), which is protected with benzyl chloroformate (XIX) to yield the carbamate (XX). The carboxylation of (XX) by means of CO, EtOH, TEA and PdCl2(PPh3)2 in ethyl acetate affords the pyridine-2-carboxylate derivative (XXI), which is finally cyclized by means of NaOMe in THF to provide the target naphthyridine derivative.

1 Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells. J Med Chem 2003, 46, 4, 453.
2 Young, S.D.; Guare, J.P.; Wai, J.S.; Payne, L.S.; Fisher, T.E.; Zhuang, L.; Embrey, M. (Merck & Co., Inc.); Aza- and polyaza-naphthalenyl ketones useful as HIV integrase inhibitors. WO 0236734 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 61832 (2-chloro-3-pyridinyl)methanamine; (2-chloro-3-pyridinyl)methylamine C6H7ClN2 详情 详情
(VII) 26991 1,3,5-tribromobenzene 626-39-1 C6H3Br3 详情 详情
(VIII) 10498 Benzaldehyde;Benzoic aldehyde;Phenylmethanal 100-52-7 C7H6O 详情 详情
(IX) 61833 (3,5-dibromophenyl)(phenyl)methanol C13H10Br2O 详情 详情
(X) 61834 1-benzyl-3,5-dibromobenzene C13H10Br2 详情 详情
(XI) 61835 3-benzyl-5-bromobenzaldehyde C14H11BrO 详情 详情
(XII) 61836 (3-benzyl-5-bromophenyl)methanol C14H13BrO 详情 详情
(XIII) 61837 1-benzyl-3-bromo-5-(bromomethyl)benzene C14H12Br2 详情 详情
(XIV) 61838 1lambda~6~-isothiazolidine-1,1-dione C3H7NO2S 详情 详情
(XV) 61839 2-(3-benzyl-5-bromobenzyl)-1lambda~6~-isothiazolidine-1,1-dione C17H18BrNO2S 详情 详情
(XVI) 61840 2-(3-acetyl-5-benzylbenzyl)-1lambda~6~-isothiazolidine-1,1-dione C19H21NO3S 详情 详情
(XVII) 61841 2-[3-benzyl-5-(2-bromoacetyl)benzyl]-1lambda~6~-isothiazolidine-1,1-dione C19H20BrNO3S 详情 详情
(XVIII) 61842 2-[3-benzyl-5-(2-{[(2-chloro-3-pyridinyl)methyl]amino}acetyl)benzyl]-1lambda~6~-isothiazolidine-1,1-dione C25H26ClN3O3S 详情 详情
(XIX) 10101 Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene 501-53-1 C8H7ClO2 详情 详情
(XX) 61843 benzyl 2-{3-benzyl-5-[(1,1-dioxo-1lambda~6~-isothiazolidin-2-yl)methyl]phenyl}-2-oxoethyl[(2-chloro-3-pyridinyl)methyl]carbamate C33H32ClN3O5S 详情 详情
(XXI) 61844 ethyl 3-({(2-{3-benzyl-5-[(1,1-dioxo-1lambda~6~-isothiazolidin-2-yl)methyl]phenyl}-2-oxoethyl)[(benzyloxy)carbonyl]amino}methyl)-2-pyridinecarboxylate C36H37N3O7S 详情 详情
Extended Information