【结 构 式】 |
【分子编号】22763 【品名】2,2-dibromo-1-(3,5-dimethoxyphenyl)-1-ethanone 【CA登记号】 |
【 分 子 式 】C10H10Br2O3 【 分 子 量 】337.9956 【元素组成】C 35.54% H 2.98% Br 47.28% O 14.2% |
合成路线1
该中间体在本合成路线中的序号:(XII)In a further procedure, 3,5-dimethoxybenzoic acid (X) was converted to the acetophenone (XI) using methyllithium. Treatment of (XI) with phenyltrimethylammonium tribromide provided the dibromoacetophenone (XII) which, upon reaction with morpholine at 55 C, followed by hydrolysis with aqueous HCl, gave the phenylglyoxal (VIII). Alternatively, (VIII) was prepared directly by treating acetophenone (XI) with DMSO and HBr or by oxidation with SeO2. Condensation of the phenylglyoxal (VIII) with methyl glyoxylate hemiacetal (XIII) and ammonium acetate produced the phenylimidazole (XIV), which was protected as the tetrahydrofuranyl derivative (XVI) with dihydrofuran and catalytic p-TsOH. Reduction of the protected imidazole ester (XVI) with LiBH4 provided alcohol (XVII), and then reaction of (XVII) with trichloroacetonitrile in the presence of DBU furnished the acetimidate (XVIII). Finally, the target compound was obtained by reaction of ascomycin (I) with trichloroacetimidate (XVIII) in the presence of fluoboric acid etherate, followed by hydrolytic deprotection.
【1】 Mathre, D.J.; Sohar, P.; Shuman, R.F.; Song, Z. (Merck & Co., Inc.); Process for the preparation of imidazolyl macrolide immunosuppressants. JP 1999512096; US 5777105; WO 9708182 . |
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) | 14951 | (1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-12-[(E)-2-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethenyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.0(4,9)]octacos-18-ene-2,3,10,16-tetron | C43H69NO12 | 详情 | 详情 | |
(VIII) | 22759 | 1-(3,5-dimethoxyphenyl)-2,2-dihydroxy-1-ethanone | C10H12O5 | 详情 | 详情 | |
(X) | 22761 | 3,5-dimethoxybenzoic acid | 1132-21-4 | C9H10O4 | 详情 | 详情 |
(XI) | 22762 | 1-(3,5-dimethoxyphenyl)-1-ethanone | 39151-19-4 | C10H12O3 | 详情 | 详情 |
(XII) | 22763 | 2,2-dibromo-1-(3,5-dimethoxyphenyl)-1-ethanone | C10H10Br2O3 | 详情 | 详情 | |
(XIII) | 22764 | methyl 2-hydroxy-2-methoxyacetate | 19757-97-2 | C4H8O4 | 详情 | 详情 |
(XIV) | 22765 | methyl 4-(3,5-dimethoxyphenyl)-1H-imidazole-2-carboxylate | C13H14N2O4 | 详情 | 详情 | |
(XV) | 22766 | 2,3-dihydrofuran | 1191-99-7 | C4H6O | 详情 | 详情 |
(XVI) | 22767 | methyl 4-(3,5-dimethoxyphenyl)-1-tetrahydro-2-furanyl-1H-imidazole-2-carboxylate | C17H20N2O5 | 详情 | 详情 | |
(XVI) | 22768 | [4-(3,5-dimethoxyphenyl)-1-tetrahydro-2-furanyl-1H-imidazol-2-yl]methanol | C16H20N2O4 | 详情 | 详情 | |
(XVIII) | 22769 | [4-(3,5-dimethoxyphenyl)-1-tetrahydro-2-furanyl-1H-imidazol-2-yl]methyl 2,2,2-trichloroethanimidoate | C18H20Cl3N3O4 | 详情 | 详情 |