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【结 构 式】 
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【药物名称】SRI-9643 【化学名称】6-(2-Chlorophenylaminomethyl)-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine 【CA登记号】 【 分 子 式 】C15H15ClN6 【 分 子 量 】314.78 |
【开发单位】Duquesne University (Originator), Indiana University (Originator) 【药理作用】AIDS Medicines, ANTIINFECTIVE THERAPY, ONCOLYTIC DRUGS, Treatment of Opportunistic Infections, Dihydrofolate Reductase (DHFR) Inhibitors |
合成路线1
Condensation of malononitrile (I) with triethyl orthoacetate (II) in pyridine produced the intermediate (III), which was cyclized to pyridine (IV) by acidic treatment. Reductive dechlorination of (IV) by hydrogenation over Pd/BaCO3 afforded 2-aminopyridine-3,5-dicarbonitrile (V). Subsequent condensation of (V) with guanidine (VI) gave rise to the pyridopyrimidine system (VII). Finally, reductive amination of (VII) with 2-chloroaniline (VIII) by means of H2 and Raney-Ni afforded the title compound.
| 【1】 Boutli, F.; Mourellou, O.; Avgoustinaki, N.; Zioga, M.; Rammnos, C.H.; Chin Journal of Medicinal Chemistry 1995, 5, 2, 79-85. |
| 【2】 Gangjee, A.; Adair, O.; Queener, S.F.; Pneumocystis carinii Toxoplasma gondii dihydrofolate reductase inhibitors and antitumor agents: Synthesis and biological activities of 2,4-diamino-5-methyl-6-[(monosubstituted anilino)methyl]-pyrido[2,3-d]pyrimidines. J Med Chem 1999, 42, 13, 2447. |
| 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) | 12061 | Malononitrile | 109-77-3 | C3H2N2 | 详情 | 详情 |
| (II) | 12940 | 1,1-Diethoxyethyl ethyl ether; 1,1,1-Triethoxyethane; Triethyl orthoacetate | 78-39-7 | C8H18O3 | 详情 | 详情 |
| (III) | 35800 | C13H9N5 | 详情 | 详情 | ||
| (IV) | 35801 | 2-amino-6-chloro-4-methyl-3,5-pyridinedicarbonitrile | C8H5ClN4 | 详情 | 详情 | |
| (V) | 35802 | 2-amino-4-methyl-3,5-pyridinedicarbonitrile | C8H6N4 | 详情 | 详情 | |
| (VI) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
| (VII) | 35803 | 2,4-diamino-5-methylpyrido[2,3-d]pyrimidine-6-carbonitrile | C9H8N6 | 详情 | 详情 | |
| (VIII) | 35804 | 2-chloroaniline; 2-chlorophenylamine | 95-51-2 | C6H6ClN | 详情 | 详情 |