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【结 构 式】 
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【分子编号】31549 【品名】N-[2-[(2,2-dimethylpropanoyl)amino]-6-[(E)-2-phenylethenyl]pyrido[2,3-d]pyrimidin-4-yl]-2,2-dimethylpropanamide 【CA登记号】 |
【 分 子 式 】C25H29N5O2 【 分 子 量 】431.53776 【元素组成】C 69.58% H 6.77% N 16.23% O 7.42% |
合成路线1
该中间体在本合成路线中的序号：(XI)In an alternative synthesis, 2,4,6-triaminopyrimidine (VI) was condensed with bromomalonaldehyde (VII) under acidic conditions to give pyridopyrimidine (VIII), which was protected with pivaloyl anhydride in pyridine, yielding the bispivaloylamide (IX). Palladium-catalyzed Heck coupling of (IX) with styrene (X) afforded (XI). Subsequent ozonolysis of the styryl derivative (XI), followed by reductive workup with dimethyl sulfide gave aldehyde (XII). Reduction of (XII) to the corresponding alcohol with NaBH4, followed by bromination with PPh3 and Br2 provided bromide (XIII). The N-methyl aniline (XIV) was synthesized by direct alkylation of 3,4,5-trimethoxyaniline (IV) with methyl iodide. Nucleophilic displacement of the bromide (XIII) with aniline (XIV) afforded the tertiary amine (XV). The pivaloyl protecting groups of (XV) were finally removed by treatment with methanolic NaOMe.
| 【1】 Gangjee, A.; et al.; Synthesis and dihydrofolate reductase inhibitory activities of 2,4-diamino-5-deaza and 2,4-diamino-5, 10-dideaza lipophilic antifolates. J Med Chem 1997, 40, 4, 470. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 31545 | 3,4,5-trimethoxyaniline; 3,4,5-trimethoxyphenylamine；3,4,5-Trimethoxybenzenamine；[3,4,5-Tris(methyloxy)phenyl]amine | 24313-88-0 | C9H13NO3 | 详情 | 详情 |
| (VI) | 28977 | 2,6-diamino-4-pyrimidinylamine | 1004-38-2 | C4H7N5 | 详情 | 详情 |
| (VII) | 14278 | 2-Bromomalonaldehyde | C3H3BrO2 | 详情 | 详情 | |
| (VIII) | 31547 | 6-bromopyrido[2,3-d]pyrimidine-2,4-diamine; 2-amino-6-bromopyrido[2,3-d]pyrimidin-4-ylamine | C7H6BrN5 | 详情 | 详情 | |
| (IX) | 31548 | N-[6-bromo-2-[(2,2-dimethylpropanoyl)amino]pyrido[2,3-d]pyrimidin-4-yl]-2,2-dimethylpropanamide | C17H22BrN5O2 | 详情 | 详情 | |
| (X) | 19649 | 1-vinylbenzene | 100-42-5 | C8H8 | 详情 | 详情 |
| (XI) | 31549 | N-[2-[(2,2-dimethylpropanoyl)amino]-6-[(E)-2-phenylethenyl]pyrido[2,3-d]pyrimidin-4-yl]-2,2-dimethylpropanamide | C25H29N5O2 | 详情 | 详情 | |
| (XII) | 31550 | N-[2-[(2,2-dimethylpropanoyl)amino]-6-formylpyrido[2,3-d]pyrimidin-4-yl]-2,2-dimethylpropanamide | C18H23N5O3 | 详情 | 详情 | |
| (XIII) | 31554 | 3-bromo-6,7,8,9-tetrahydro-5H-benzo[a]cyclohepten-5-one | C11H11BrO | 详情 | 详情 | |
| (XIV) | 31552 | 3,4,5-trimethoxy-N-methylaniline; N-methyl-N-(3,4,5-trimethoxyphenyl)amine | C10H15NO3 | 详情 | 详情 | |
| (XV) | 31553 | N-(2-[(2,2-dimethylpropanoyl)amino]-6-[[3,4,5-trimethoxy(methyl)anilino]methyl]pyrido[2,3-d]pyrimidin-4-yl)-2,2-dimethylpropanamide | C28H38N6O5 | 详情 | 详情 |