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【结 构 式】 
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【分子编号】59645 【品名】2-Fluoro-5-methylpyridine; 6-Fluoro-3-picoline 【CA登记号】2369-19-9 |
【 分 子 式 】C6H6FN 【 分 子 量 】111.1187832 【元素组成】C 64.85% H 5.44% F 17.1% N 12.61% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)Acylation of ethyl 3-(methylamino)crotonate (IX) with 2-chloro-6-fluorobenzoyl chloride (X) provided the enamino ketoester (XI), which was cyclized to the isoxazole derivative (XII) upon treatment with hydroxylamine. Hydrolysis of ethyl ester (XII), followed by chlorination of the resultant acid (XIII), furnished acid chloride (XIV). This was condensed with amine (VIII) affording amide (XV). The isoxazoloquinoline derivative (XVI) was then obtained by cyclization of fluoro amide (XV) in the presence of potassium bis(trimethylsilyl)amide. Removal of the N-Cbz group of (XVI) using iodotrimethylsilane in CH2Cl2 yielded amine (XVII). 6-Fluoronicotinic acid (XIX) was prepared by permanganate oxidation of 2-fluoro-6-methylpyridine (XVIII). Finally, amine (XVII) was coupled with 6-fluoronicotinic acid (XIX) by means of EDC to furnish the title compound.
| 【1】 Methods and cpds. for inhibiting MRP1. EP 1250340; WO 0146199 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 59635 | benzyl [(1R,3S)-3-aminocyclohexyl]methylcarbamate | C15H22N2O2 | 详情 | 详情 | |
| (IX) | 59636 | ethyl (E)-3-(methylamino)-2-butenoate | C7H13NO2 | 详情 | 详情 | |
| (X) | 59637 | 2-Chloro-6-fluorobenzoyl chloride | 79455-63-3 | C7H3Cl2FO | 详情 | 详情 |
| (XI) | 59638 | ethyl (E)-2-(2-chloro-6-fluorobenzoyl)-3-(methylamino)-2-butenoate | C14H15ClFNO3 | 详情 | 详情 | |
| (XII) | 59639 | ethyl 3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolecarboxylate | C13H11ClFNO3 | 详情 | 详情 | |
| (XIII) | 59640 | 3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolecarboxylic acid | C11H7ClFNO3 | 详情 | 详情 | |
| (XIV) | 59641 | 3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolecarbonyl chloride | C11H6Cl2FNO2 | 详情 | 详情 | |
| (XV) | 59642 | benzyl [(1R,3S)-3-({[3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl]carbonyl}amino)cyclohexyl]methylcarbamate | C26H27ClFN3O4 | 详情 | 详情 | |
| (XVI) | 59643 | benzyl {(1R,3S)-3-[9-chloro-3-methyl-4-oxoisoxazolo[4,3-c]quinolin-5(4H)-yl]cyclohexyl}methylcarbamate | C26H26ClN3O4 | 详情 | 详情 | |
| (XVII) | 59644 | 5-[(1S,3R)-3-(aminomethyl)cyclohexyl]-9-chloro-3-methylisoxazolo[4,3-c]quinolin-4(5H)-one | C18H20ClN3O2 | 详情 | 详情 | |
| (XVIII) | 59645 | 2-Fluoro-5-methylpyridine; 6-Fluoro-3-picoline | 2369-19-9 | C6H6FN | 详情 | 详情 |
| (XIX) | 59646 | 6-fluoronicotinic acid | C6H4FNO2 | 详情 | 详情 |