反应 #2314342

反应方程式

4-hydroxy-7-methyl[1,8]naphthyridine-3-carboxylic acid

4-chlorobenzylamine

phosphorus trichloride

→

desired product

收率 5.0%

N-(4-chlorobenzyl)-4-hydroxy-7-methyl[1,8]naphthyridine-3-carboxamide

收率 5.0%

溶剂

water

反应条件

后处理

1. 1
   温度Refluxing
2. 2
   温度The mixture is cooled
3. 3
   其他to destroy excess PCl3
4. 4
   其他The solvents are removed
5. 5
   其他The residue is partitioned between EtOAc and water
6. 6
   萃取The aqueous layer is extracted with EtOAc (3×)
7. 7
   洗涤The combined organic layers are washed with brine (1×)
8. 8
   其他dried
9. 9
   其他condensed
10. 10
    其他chromatographed (eluent 5% MeOH/CH2Cl2)
11. 11
    其他condensed
12. 12
    其他triturated with Et2O/hexanes

实验过程

A solution of 4-hydroxy-7-methyl[1,8]naphthyridine-3-carboxylic acid (0.204 g) and 4-chlorobenzylamine (0.12 mL) is heated to reflux. To this is added dropwise phosphorus trichloride (0.04 mL). Refluxing is continued for 3 h. The mixture is cooled and water is added to destroy excess PCl3. The solvents are removed. The residue is partitioned between EtOAc and water. The aqueous layer is extracted with EtOAc (3×). The combined organic layers are washed with brine (1×), dried and condensed. The residue is adsorbed on silica and chromatographed (eluent 5% MeOH/CH2Cl2). Fractions homogeneous by TLC are condensed and triturated with Et2O/hexanes to yield 0.017 g (5%) of the desired product as a yellow solid. Physical characteristics are as follows: m.p. 280-285° C. (dec); 1H NMR (300 MHz, DMSO) δ 13.0, 10.20, 8.63, 8.47, 7.38, 4.52, 2.61; IR (mull) 3186, 3148, 3055, 3034, 1655, 1605, 1570, 1546, 1494, 1333, 1243, 1097, 814, 799, 623 cm−1; MS (EI) m/z 327 (M+), 188, 187, 161, 160, 142, 140, 132, 131, 104; HRMS (EI) calcd for C17H14ClN3O2 327.0775, found 327.0783.

来源