【结 构 式】 |
【分子编号】48450 【品名】dimethyl [[(2,3-dimethoxy-7-nitro-5-quinoxalinyl)methyl]amino]methylphosphonate 【CA登记号】 |
【 分 子 式 】C14H19N4O7P 【 分 子 量 】386.301382 【元素组成】C 43.53% H 4.96% N 14.5% O 28.99% P 8.02% |
合成路线1
该中间体在本合成路线中的序号:(XII)Treatment of diamino compound (I) with oxalic acid (II) in refluxing HCl provides tetrahydroquinoxalindione derivative (III), which is then converted into dichloro compound (IV) by reaction with refluxing POCl3. Treatment of (IV) with Na in refluxing MeOH affords dimethoxy quinoxaline (V), which is then brominated by reaction with NBS and AIBN in refluxing CCl4 to give bromomethyl derivative (VI). Nitration of (VI) by reaction with isopropyl nitrate in H2SO4 yields nitro derivative (VII), which is then converted into protected amino methyl derivative (IX) by reaction with di-tert-butyl-iminocarboxylate (VIII) and cesium carbonate in DMF. Removal of the Boc groups of (IX) by means of TFA gives aminomethyl derivative (X), which is then converted into phosphonic dimethyl ester (XII) by first treatment with formaline in EtOH followed by reaction with dimethyl phosphonate (XI), Et3N and trimethylsilyl chloride (TMSCl) in CHCl3. Finally, treatment of (XII) with trimethylsilyl bromide (TMSBr) in CH2Cl2 obtains the desired product.
【1】 Acklin, P.; Allgeier, H.; Auberson, Y.; Ofner, S.; Veenstra, S.J. (Novartis AG); Substd. aminoalkane phosphonic acids. EP 0934326; US 6117873; WO 9817672 . |
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) | 48441 | 2,3-Diaminotoluene; o-Tolylenediamine | 2687-25-4 | C7H10N2 | 详情 | 详情 |
(II) | 15713 | Oxalic acid | 144-62-7 | C2H2O4 | 详情 | 详情 |
(III) | 48442 | 5-methyl-1,4-dihydro-2,3-quinoxalinedione | C9H8N2O2 | 详情 | 详情 | |
(IV) | 48443 | 2,3-dichloro-5-methylquinoxaline | C9H6Cl2N2 | 详情 | 详情 | |
(V) | 48444 | 2,3-dimethoxy-5-methylquinoxaline; 3-methoxy-5-methyl-2-quinoxalinyl methyl ether | C11H12N2O2 | 详情 | 详情 | |
(VI) | 48445 | 5-(bromomethyl)-3-methoxy-2-quinoxalinyl methyl ether; 5-(bromomethyl)-2,3-dimethoxyquinoxaline | C11H11BrN2O2 | 详情 | 详情 | |
(VII) | 48446 | 5-(bromomethyl)-3-methoxy-7-nitro-2-quinoxalinyl methyl ether; 5-(bromomethyl)-2,3-dimethoxy-7-nitroquinoxaline | C11H10BrN3O4 | 详情 | 详情 | |
(VIII) | 48447 | Di-tert-butyl iminodicarboxylate; Iminodicarboxylic acid di-tert-butyl ester | 51779-32-9 | C10H19NO4 | 详情 | 详情 |
(IX) | 48448 | 5-[[bis(tert-butoxycarbonyl)amino]methyl]-2,3-dimethoxy-7-nitroquinoxaline | C21H28N4O8 | 详情 | 详情 | |
(X) | 48449 | (2,3-dimethoxy-7-nitro-5-quinoxalinyl)methanamine; (2,3-dimethoxy-7-nitro-5-quinoxalinyl)methylamine | C11H12N4O4 | 详情 | 详情 | |
(XI) | 32359 | dimethyl phosphonate | 868-85-9 | C2H7O3P | 详情 | 详情 |
(XII) | 48450 | dimethyl [[(2,3-dimethoxy-7-nitro-5-quinoxalinyl)methyl]amino]methylphosphonate | C14H19N4O7P | 详情 | 详情 |