反应详情

A solution of 4-methyl-3-(1-morpholinophthalazin-6-yl)benzoic acid (Example 8, 160 mg, 0.45 mmol) in thionyl chloride (1.0 mL, 1.37 mmol) was stirred at RT for 1 h. Excess SOCl2 was removed under reduced pressure and the residue was treated with 1 mL of toluene and concentrated under reduced pressure. The residue was dissolved in dichloromethane (3 mL), and isoxazol-3-amine (58 mg, 0.69 mmol) followed by pyridine (72 mg, 0.92 mmol) was added. After the resulting mixture was refluxed for 1 h, cooled to RT, diluted with dichloromethane, and washed with 1 N NaOH. The dichloromethane layer was dried, concentrated, and purified on an ISCO 12 g column (eluted with 5-15% MeOH in ethyl acetate) to provide N-(isoxazol-3-yl)-4-methyl-3-(1-morpholinophthalazin-6-yl)benzamide as an amorphous off-white solid. Found MS (ESI, pos. ion) m/z: 416 (M+1).

1. customExcess SOCl2 was removed under reduced pressure
2. additionthe residue was treated with 1 mL of toluene
3. concentrationconcentrated under reduced pressure
4. dissolutionThe residue was dissolved in dichloromethane (3 mL)
5. additionwas added
6. temperatureAfter the resulting mixture was refluxed for 1 h
7. washwashed with 1 N NaOH
8. dry with materialThe dichloromethane layer was dried
9. concentrationconcentrated
10. custompurified on an ISCO 12 g column (eluted with 5-15% MeOH in ethyl acetate)