反应详情

A solution of 6-bromo-N-(4-chlorobenzyl)-4-hydroxy-7-methyl[1,8]naphthyridine-3-carboxamide (0.244 g, 0.60 mmol), propargyl alcohol (0.047 g, 0.84 mmol), triethylamine (0.38 mL) and PdCl2(PPh3)2 (0.023 g, 0.03 mmol) 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) δ13.19, 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 C20H16CIN3O3 +H1 382.0958, found 382.0960.

1. temperatureThe resulting solution is cooled
2. custompartitioned between EtOAc and water
3. customThe solid which formed
4. filtrationis filtered
5. extractionThe aqueous layer is extracted with EtOAc (3×)
6. washThe combined organic layers are washed with brine
7. customdried
8. customcondensed
9. customThe crude product is chromatographed on silica (Biotage flash 40S, eluent 2% MeOH/CH2Cl2
10. customcondensed