反应 #2314345

反应方程式

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

propargyl alcohol

triethylamine

→

desired product

收率 35.4%

N-(4-chlorobenzyl)-4-hydroxy-6-(3-hydroxy-1-propynyl)-7-methyl[1,8]naphthyridine-3-carboxamide

收率 35.4%

溶剂

DMF

反应条件

后处理

1. 1
   温度The resulting solution is cooled
2. 2
   其他partitioned between EtOAc and water
3. 3
   其他The solid which formed
4. 4
   过滤is filtered
5. 5
   萃取The aqueous layer is extracted with EtOAc (3×)
6. 6
   洗涤The combined organic layers are washed with brine
7. 7
   其他dried
8. 8
   其他condensed
9. 9
   其他The crude product is chromatographed on silica (Biotage flash 40S, eluent 2% MeOH/CH2Cl2
10. 10
    其他condensed

实验过程

A solution of 6-bromo-N-(4-chlorobenzyl)-4-hydroxy-7-methyl[1,8]naphthyridine-3-carboxamide (Ex 2. 0.244 g), propargyl alcohol (0.047 g), triethylamine (0.38 mL) and PdCl2(PPh3)2 (0.023 g) in 3 mL DMF is heated to 90° C. for 2.5 h. The resulting solution is cooled and partitioned between EtOAc and water. The solid which formed is filtered and discarded. The aqueous layer is extracted with EtOAc (3×). The combined organic layers are washed with brine, dried and condensed. The crude product is chromatographed on silica (Biotage flash 40S, eluent 2% MeOH/CH2Cl2 then 3% MeOH/CH2Cl2. Fractions homogeneous by TLC are combined and condensed to yield 0.081 g (35%) of the desired product as a yellow solid. Physical characteristics are as follows: m.p. 279-281° C. (dec.); 1H NMR (DMSO-d6) δ 13.19, 10.12, 8.64, 8.43, 7.38, 5.46, 4.54, 4.40, 2.71; IR (drift) 3194, 3065, 2944, 1645, 1597, 1566, 1522, 1488, 1418, 1357, 1257, 1208, 1015, 851, 809 cm−1; OAMS supporting ions at: ESI+381.9 ESI−379.9; HRMS (FAB) calcd for C20H16ClN3O3 +H1 382.0958, found 382.0960.

来源