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【结 构 式】 
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【分子编号】36315 【品名】N-benzyl-2-chloro-9H-purin-6-amine; N-benzyl-N-(2-chloro-9H-purin-6-yl)amine 【CA登记号】 |
【 分 子 式 】C12H10ClN5 【 分 子 量 】259.6978 【元素组成】C 55.5% H 3.88% Cl 13.65% N 26.97% |
合成路线1
该中间体在本合成路线中的序号：(VI)Adenine (I) was oxidized with hydrogen peroxide in aqueous acetic acid to give adenine 1-N-oxide (II). Diazotization of (II) with sodium nitrite and acetic acid, followed by hydrolysis of the diazonium salt provided hypoxanthine 1-N-oxide (III). 2,6-Dichloropurine (IV) was then obtained by treatment of (III) with phosphoryl chloride in the presence of triethylamine. Displacement of the 6-chlorine atom of (IV) by benzylamine (V) in boiling n-butanol yielded 6-benzylamino-2-chloropurine (VI), which was subsequently alkylated at the 9-N with isopropyl iodide and NaH to give (VII). Finally, the remaining 2-chloro atom of (VII) was displaced by thiomorpholine (VIII) to furnish the title compound.
| 【1】 Woo, E.-R.; Baek, D.J.; Lee, s.-C.; Hong, C.Y.; Lee, K.-S.; Yang, B.-S.; Cho, J.-H.; Oh, C.-H.; Synthesis and biological activities of C-2, N-9 substituted 6-benzylaminopurine derivatives as cyclin-dependent kinase inhibitor. Arch Pharm 1999, 332, 6, 187. |
| 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) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (II) | 36313 | 6-amino-9H-purin-1-ium-1-olate | C5H5N5O | 详情 | 详情 | |
| (III) | 36314 | 6-hydroxy-9H-purin-1-ium-1-olate | C5H4N4O2 | 详情 | 详情 | |
| (IV) | 25254 | 2,6-dichloro-9H-purine | 5451-40-1 | C5H2Cl2N4 | 详情 | 详情 |
| (V) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (VI) | 36315 | N-benzyl-2-chloro-9H-purin-6-amine; N-benzyl-N-(2-chloro-9H-purin-6-yl)amine | C12H10ClN5 | 详情 | 详情 | |
| (VII) | 36316 | N-benzyl-2-chloro-9-isopropyl-9H-purin-6-amine; N-benzyl-N-(2-chloro-9-isopropyl-9H-purin-6-yl)amine | C15H16ClN5 | 详情 | 详情 | |
| (VIII) | 36317 | thiomorpholine | 123-90-0 | C4H9NS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Condensation of 2,6-dichloropurine (I) with benzylamine (II) in boiling butanol afforded 6-(benzylamino)-2-chloropurine (III), which was subsequently alkylated at the 9-N with isopropyl bromide (IV), yielding purine (V). The 2-chloro group was finally displaced with (R)-2-amino-1-butanol (VI) in a sealed tube at 160 C to provide the title compound.
| 【1】 Wang, S.; et al.; Synthesis and configuration of the cyclin-dependent kinase inhibitor roscovitine and its enantiomer. Tetrahedron Asymmetry 2001, 12, 20, 2891. |
| 【2】 Havlicek, L.; et al.; Cytokinin-derived cyclin-dependent kinase inhibitors: Synthesis and cdc2 inhibitory activity of olomoucine and related compounds. J Med Chem 1997, 40, 4, 408. |
| 【3】 Meijer, L.; Bisagni, E.; Legraverend, M. (CNRS (Centre National de la Recherche Scientifique)); Novel purine derivs. having, in particular, antiproliferative properties, and biological uses thereof. EP 0874847; FR 2741881; JP 2000501408; US 2002049218; US 6316456; WO 9720842 . |
| 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) | 25254 | 2,6-dichloro-9H-purine | 5451-40-1 | C5H2Cl2N4 | 详情 | 详情 |
| (II) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |
| (III) | 36315 | N-benzyl-2-chloro-9H-purin-6-amine; N-benzyl-N-(2-chloro-9H-purin-6-yl)amine | C12H10ClN5 | 详情 | 详情 | |
| (IV) | 32658 | 2-bromopropane | 75-26-3 | C3H7Br | 详情 | 详情 |
| (V) | 36316 | N-benzyl-2-chloro-9-isopropyl-9H-purin-6-amine; N-benzyl-N-(2-chloro-9-isopropyl-9H-purin-6-yl)amine | C15H16ClN5 | 详情 | 详情 | |
| (VI) | 48572 | (S)-(+)-2-Amino-1-butanol; L-(+)-2-Amino-1-butanol; (S)-2-Amino-1-butanol | 5856-62-2 | C4H11NO | 详情 | 详情 |