|
【结 构 式】 
|
【分子编号】23829 【品名】1-phenyl-1,3-butanedione 【CA登记号】93-91-4 |
【 分 子 式 】C10H10O2 【 分 子 量 】162.1882 【元素组成】C 74.06% H 6.21% O 19.73% |
合成路线1
该中间体在本合成路线中的序号：(IV)The intermediate 4-bromothiophene-3-carboxylic acid (II) was prepared in low yield by lithium-halogen exchange of 3,4-dibromothiophene (I) with n-BuLi in Et2O at -78 C, followed by quenching with solid CO2. Alternatively, lithiation of (I) at -116 C and further quenching with ethyl chloroformate provided ethyl ester (III) in moderate yields, accompanied by some byproducts that were separated by column chromatography. The required carboxylic acid (II) was then formed by saponification of (III) with NaOH. Subsequent condensation of bromoacid (II) with benzoylacetone (IV) either in the presence of sodium ethoxide and copper powder or NaH and CuBr proceeded with concomitant retro-Claisen cleavage to provide monoketone (V). The target thienopyridinone was then obtained by cyclization of (V) with ammonium acetate in refluxing AcOH.
| 【1】 Shinkwin, A.E.; et al.; Synthesis of thiophenecarboxamides, thieno[3,4-c]p. Bioorg Med Chem 1999, 7, 2, 297. |
| 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) | 23826 | 3,4-dibromothiophene | 3141-26-2 | C4H2Br2S | 详情 | 详情 |
| (II) | 23827 | 4-bromo-3-thiophenecarboxylic acid | C5H3BrO2S | 详情 | 详情 | |
| (III) | 23828 | ethyl 4-bromo-3-thiophenecarboxylate | C7H7BrO2S | 详情 | 详情 | |
| (IV) | 23829 | 1-phenyl-1,3-butanedione | 93-91-4 | C10H10O2 | 详情 | 详情 |
| (V) | 23830 | 4-(2-oxo-2-phenylethyl)-3-thiophenecarboxylic acid | C13H10O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)The cyclization of methyl 4-bromo-3-oxopentanoate (I) with benzamide (II) and sodium hydrogen phosphate in refluxing ethanol gives methyl 2-(5-methyl-2-phenyloxazol-4-yl)acetate (III), which is reduced with LiAlH4 in THF to yield the ethanol derivative (IV). The reaction of (IV) with methanesulfonyl chloride and TEA in dichloromethane affords the mesylate (V), which is condensed with N-(tert-butoxycarbonyl)-L-tyrosine (VI) by means of NaOH in hot DMSO/water to provide the 4-O-substituted tyrosine (VII), which is deprotected by means of HCl in dioxane to give intermediate (VIII) with a free amino group. Finally, this compound is condensed with benzoylacetone (IX) by means of trimethyl orthoformate in refluxing methanol to afford the target N-substituted tyrosine derivative.
| 【1】 Oplinger, J.A.; Dezube, M.; Willson, T.M.; Collins, J.L. (Glaxo Group Ltd.); Substd. oxazoles and thiazoles derivs. as hPPAR gamma and hPPAR alpha activators. EP 1102757; WO 0008002 . |
| 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) | 49397 | methyl 4-bromo-3-oxopentanoate | C6H9BrO3 | 详情 | 详情 | |
| (II) | 40592 | Benzamide | 55-21-0 | C7H7NO | 详情 | 详情 |
| (III) | 41313 | methyl 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)acetate | C13H13NO3 | 详情 | 详情 | |
| (IV) | 19874 | 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-1-ethanol | C12H13NO2 | 详情 | 详情 | |
| (V) | 41315 | 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethyl methanesulfonate | C13H15NO4S | 详情 | 详情 | |
| (VI) | 25395 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propionic acid | 3978-80-1 | C14H19NO5 | 详情 | 详情 |
| (VII) | 49398 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propionic acid | C26H30N2O6 | 详情 | 详情 | |
| (VIII) | 49399 | (2S)-2-amino-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propionic acid | C21H22N2O4 | 详情 | 详情 | |
| (IX) | 23829 | 1-phenyl-1,3-butanedione | 93-91-4 | C10H10O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)The title dihydropyridine is prepared by condensation of benzoylacetone (I) with 3-chlorobenzaldehyde (II) in the presence of aqueous ammonia, following a variation of the Hantzsch reaction.
