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【结 构 式】 
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【药物名称】ZK-260255, AAL-993 【化学名称】2-(Pyridin-4-ylmethylamino)-N-[3-(trifluoromethyl)phenyl]benzamide 【CA登记号】269390-77-4 【 分 子 式 】C20H16F3N3O 【 分 子 量 】371.36522 |
【开发单位】Novartis (Originator), Schering AG (Originator) 【药理作用】Oncolytic Drugs, Angiogenesis Inhibitors, VEGFR-2 (FLK-1/KDR) Inhibitors, VEGFR-3 (FLT4) Inhibitors |
合成路线1
The intermediate anthranilamide (IV) is prepared by two alternative methods. Acylation of 3-(trifluoromethyl)aniline (I) with 2-nitrobenzoyl chloride (II) yields benzamide (III). The nitro group of (III) is then reduced to the corresponding amine (IV) by catalytic hydrogenation over Pd/C (1). Alternatively, 3-(trifluoromethyl)aniline (I) is condensed with isatoic anhydride (V) to furnish directly anthranilamide (IV) (2). Finally, reductive alkylation of (IV) with pyridine-4-carbaldehyde (VI) employing NaBH3CN gives rise to the target pyridylmethyl amine.
| 【1】 Manley, P.W.; Furet, P.; Bold, G.; Bruggen, J.; Mestan, J.; Meyer, T.; Schnell, C.R.; Wood, J.; Anthranilic acid amides: A novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem 2002, 45, 26, 5687. |
| 【2】 Seidelmann, D.; Huth, A.; Manley, P.W.; Thierauch, K.-H.; Krüger, M.; Bold, G.; Haberey, M.; Furet, P.; Altmann, K.-H.; Mestan, J.; Menrad, A.; Ferrari, S.; Wood, J.M.; Hofmann, F. (Novartis AG; Schering AG); N-Aryl(thio)anthranilic acid amide derivs., their preparation and their use as VEGF receptor tyrosine kinase inhibitors. EP 1129075; JP 2002529453; US 6448277; WO 0027820 . |
| 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) | 26347 | 3-(trifluoromethyl)phenylamine; 3-(trifluoromethyl)aniline; 3-aminobenzotrifluoride | 98-16-8 | C7H6F3N | 详情 | 详情 |
| (II) | 21099 | o-nitrobenzoyl chloride; 2-nitrobenzoyl chloride | 610-14-0 | C7H4ClNO3 | 详情 | 详情 |
| (III) | 64309 | 2-nitro-N-[3-(trifluoromethyl)phenyl]benzamide | C14H9F3N2O3 | 详情 | 详情 | |
| (IV) | 64310 | 2-amino-N-[3-(trifluoromethyl)phenyl]benzamide | C14H11F3N2O | 详情 | 详情 | |
| (V) | 29797 | 2H-3,1-benzoxazine-2,4(1H)-dione；Isatoic anhydride;4H-3,1-Benzoxazine-2,4(1H)-dione；1,2-Dihydro-4H-3,1-benzoxazine-2,4-dione;1H-benzo[d][1,3]oxazine-2,4-dione | 118-48-9 | C8H5NO3 | 详情 | 详情 |
| (VI) | 17203 | 4-Pyridinecarboxaldehyde; isonicotinaldehyde | 872-85-5 | C6H5NO | 详情 | 详情 |