反应详情

温度

100 °C

To a 50 ml round-bottomed flask was added 2-(quinolin-6-yl)acetic acid (0.60 g, 3.2 mmol), CH2Cl2 (20 ml) and oxalyl chloride (4.0 ml, 8.0 mmol, 2 M in CH2Cl2) and DMF (0.2 mL of a solution of 1 drop DMF in 1 mL CH2Cl2). After 3 d, an additional 2.5 eq. of oxalyl chloride was added. After 4 h, toluene (1 mL) was added and the mixture was concentrated. Toluene (3 mL) was added and again concentrated. The residue was taken up in CH2Cl2 (20 mL) and 1-(6-phenylpyridazin-3-yl)hydrazine (0.60 g, 3.2 mmol) was added. The mixture was stirred for 17 h and then concentrated. The mixture was then taken up in phosphorous oxychloride (20 ml, 220 mmol) and heated at 100° C. for 15 h. Toluene (5 mL) was added and the solution was concentrated. Another 5 mL toluene was added to the residue and once again it was concentrated. The brown solid residue was taken up in sat. NaHCO3 and extracted with EtOAc (4×150 mL) and 25% iPrOH/CHCl3 (3×150 mL). The combined extracts were washed with brine, dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (0 to 5% MeOH (2M in NH3)/CH2Cl2) afforded the title compound as a tan solid. MS (ESI, pos. ion) m/z: 338 (M+1).

1. waitAfter 4 h
2. concentrationthe mixture was concentrated
3. additionToluene (3 mL) was added
4. concentrationagain concentrated
5. concentrationconcentrated
6. concentrationthe solution was concentrated
7. additionAnother 5 mL toluene was added to the residue and once again it
8. concentrationwas concentrated
9. extractionextracted with EtOAc (4×150 mL) and 25% iPrOH/CHCl3 (3×150 mL)
10. washThe combined extracts were washed with brine
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated onto silica
13. customPurification by silica gel chromatography (0 to 5% MeOH (2M in NH3)/CH2Cl2)