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【结 构 式】 
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【分子编号】47618 【品名】6-(bromomethyl)-2,4-quinazolinediamine; 2-amino-6-(bromomethyl)-4-quinazolinylamine 【CA登记号】 |
【 分 子 式 】C9H9BrN4 【 分 子 量 】253.10142 【元素组成】C 42.71% H 3.58% Br 31.57% N 22.14% |
合成路线1
该中间体在本合成路线中的序号：(I)Title compound is obtained by condensation of 6-(bromomethyl)pteridine-2,4-diamine (I) with dibenz[b,f]azepine (II) by means of NaH in THF..
| 【2】 Rosowsky, A. (Dana-Farber Cancer Institute); Pharmaceutically active cpds. and methods of use thereof. WO 0059884 . |
| 【1】 Cody, V.; Papoulis, A.T.; Rosowsky, A.; Galitsky, N.; Fu, H.; Queener, S.F.; Structure-based design of selective inhibitors of dihydrofolate reductase: Synthesis and antiparasitic activity of 2,4-diaminopteridine analogues with a bridged diarylamine side chain. J Med Chem 1999, 42, 23, 4853. |
合成路线2
该中间体在本合成路线中的序号：(V)Nitrile (II) was prepared by regioselective diazotization of triaminoquinazoline (I), followed by treatment with KCN and CuSO4. Conversion of nitrile (II) into aldehyde (III) was achieved by means of Ni-Al alloy in refluxing formic acid. Subsequent reduction of aldehyde (III) with NaBH4 gave alcohol (IV), which was further brominated to (V) using HBr in HOAc. Finally, displacement of the bromide of (V) with 3,4,5-trimethoxybenzoic acid (VI) provided the target trimethoxybenzoate ester.
| 【1】 Graffner-Nordberg, M.; et al.; Design, synthesis, computational prediction, and biological evaluation of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii. J Med Chem 2001, 44, 15, 2391. |
| 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) | 52638 | 2,4,6-quinazolinetriamine | 13741-90-7 | C8H9N5 | 详情 | 详情 |
| (II) | 52639 | 2,4-diamino-6-quinazolinecarbonitrile | C9H7N5 | 详情 | 详情 | |
| (III) | 52640 | 2,4-diamino-6-quinazolinecarbaldehyde | C9H8N4O | 详情 | 详情 | |
| (IV) | 52641 | (2,4-diamino-6-quinazolinyl)methanol | C9H10N4O | 详情 | 详情 | |
| (V) | 47618 | 6-(bromomethyl)-2,4-quinazolinediamine; 2-amino-6-(bromomethyl)-4-quinazolinylamine | C9H9BrN4 | 详情 | 详情 | |
| (VI) | 32225 | 3,4,5-trimethoxybenzoic acid | 118-41-2 | C10H12O5 | 详情 | 详情 |