|
【结 构 式】 
|
【分子编号】54801 【品名】2-Fluoro-4-nitrophenol; 4-Nitro-2-fluorophenol 【CA登记号】403-19-0 |
【 分 子 式 】C6H4FNO3 【 分 子 量 】157.1011032 【元素组成】C 45.87% H 2.57% F 12.09% N 8.92% O 30.55% |
合成路线1
该中间体在本合成路线中的序号：(IV)Addition of formaldehyde to benzothiophene-2-sulfonamide (I), followed by condensation with trimethyl phosphite, furnished the dimethyl (sulfonamidomethyl)phosphonate (II). The phosphonate ester function of (II) was then hydrolyzed by means of bromotrimethylsilane, producing phosphonic acid (III). This was finally coupled to 2-fluoro-4-nitrophenol (IV) using trichloroacetonitrile in hot pyridine to afford the title mono-phosphonate ester.
| 【1】 Stutz, A. (Novartis AG); Propenylamines, pharmaceutical compositions containing them and their use as pharmaceuticals. EP 0024587; JP 56032440; JP 63313753; Us 4755534 . |
| 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) | 54798 | 1-benzothiophene-2-sulfonamide | C8H7NO2S2 | 详情 | 详情 | |
| (II) | 54799 | dimethyl [(1-benzothiophen-2-ylsulfonyl)amino]methylphosphonate | C11H14NO5PS2 | 详情 | 详情 | |
| (III) | 54800 | [(1-benzothiophen-2-ylsulfonyl)amino]methylphosphonic acid | C9H10NO5PS2 | 详情 | 详情 | |
| (IV) | 54801 | 2-Fluoro-4-nitrophenol; 4-Nitro-2-fluorophenol | 403-19-0 | C6H4FNO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXIII)The 4-(aminophenoxy)quinoline precursor (VII) can be obtained from chloroquinoline (VI) by two related methods. Condensation of chloride (VI) with 2-fluoro-4-nitrophenol (XXXIII) in 2,6-lutidine at 140-145 °C affords the 2-fluoro-4-nitrophenyl ether (XXXIV), which is then reduced by catalytic hydrogenation over Pd/C in the presence of HCl in H2O/EtOH .
Alternatively, by direct coupling of chloroquinoline (VI) with 2-fluoro-4-aminophenol (XVI) by means of sodium tert-butoxide in DMAc at 100 °C .
| 【1】 Wilson, J., Zuberi, S., Naganathan, S., Goldman, E., Kanter, J. (Exelixis, Inc.). Methods of preparing quinoline derivatives. WO 2010056960. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 69105 | 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinoline;4-(3-((4-chloro-6-methoxyquinolin-7-yl)oxy)propyl)morpholine | C17H21ClN2O3 | 详情 | 详情 | |
| (VII) | 69106 | 3-fluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)aniline | C23H26FN3O4 | 详情 | 详情 | |
| (XVI) | 69111 | 4-amino-2-fluorophenol;2-Fluoro-4-aminophenol | 399-96-2 | C6H6FNO | 详情 | 详情 |
| (XXXIII) | 54801 | 2-Fluoro-4-nitrophenol; 4-Nitro-2-fluorophenol | 403-19-0 | C6H4FNO3 | 详情 | 详情 |
| (XXXIV) | 69122 | 4-(3-((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-yl)oxy)propyl)morpholine | C23H24FN3O6 | 详情 | 详情 |