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【结 构 式】 
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【分子编号】51973 【品名】2-Fluoro-4-chloroaniline; 4-Chloro-2-fluorobenzenamine; 4-Chloro-2-fluoroaniline 【CA登记号】57946-56-2 |
【 分 子 式 】C6H5ClFN 【 分 子 量 】145.5635432 【元素组成】C 49.51% H 3.46% Cl 24.36% F 13.05% N 9.62% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The condensation of 7-hydroxy-6-methoxy-3-(pivaloyloxymethyl)quinazolin-3(4H)-one (I) with N-(tert-butoxycarbonyl)piperidine-4-methanol (II) by means of DEAD and PPh3 in dichloromethane or K2CO3 in DMF gives the aryl ether (III), which is deprotected with TFA to yield the free piperidine (IV). The reductive methylation of (IV) with HCHO and NaBH3CN in methanol/THF affords the methylated piperidine (V), which is deprotected with NH3 in methanol to provide the quinazolinone (VI). The reaction of (VI) with SOCl2 in DMF gives the 4-chloroquinazoline (VII), which is finally condensed with 4-chloro-2-fluoroaniline (VIII) by means of NaH in DMF to yield the target quinazoline-4-amine.
| 【1】 Hennequin, L.F.; et al.; Novel 4-anilinoquinazolines with C-7 basic side chains: Design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors. J Med Chem 2002, 45, 6, 1300. |
| 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) | 51967 | [7-hydroxy-6-methoxy-4-oxo-3(4H)-quinazolinyl]methyl pivalate | C15H18N2O5 | 详情 | 详情 | |
| (II) | 40399 | tert-butyl 4-(hydroxymethyl)-1-piperidinecarboxylate | C11H21NO3 | 详情 | 详情 | |
| (III) | 51968 | tert-butyl 4-[[(3-[[(2,2-dimethylpropanoyl)oxy]methyl]-6-methoxy-4-oxo-3,4-dihydro-7-quinazolinyl)oxy]methyl]-1-piperidinecarboxylate | C26H37N3O7 | 详情 | 详情 | |
| (IV) | 51969 | [6-methoxy-4-oxo-7-(4-piperidinylmethoxy)-3(4H)-quinazolinyl]methyl pivalate | C21H29N3O5 | 详情 | 详情 | |
| (V) | 51971 | [6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-4-oxo-3(4H)-quinazolinyl]methyl pivalate | C22H31N3O5 | 详情 | 详情 | |
| (VI) | 51970 | 6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]-4(3H)-quinazolinone | C16H21N3O3 | 详情 | 详情 | |
| (VII) | 51972 | 4-chloro-6-methoxy-7-quinazolinyl (1-methyl-4-piperidinyl)methyl ether; 4-chloro-6-methoxy-7-[(1-methyl-4-piperidinyl)methoxy]quinazoline | C16H20ClN3O2 | 详情 | 详情 | |
| (VIII) | 51973 | 2-Fluoro-4-chloroaniline; 4-Chloro-2-fluorobenzenamine; 4-Chloro-2-fluoroaniline | 57946-56-2 | C6H5ClFN | 详情 | 详情 |