反应详情

Thionyl chloride (625 μl, 8.6 mmol) was added to a stirred suspension of [1-methyl-4-({[3-(5-methylisoxazol-3-yl)[1,2,4]triazolo[3,4-α]phthalazine-6-yl]oxy}methyl)-1H-[1,2,3]triazol-5-yl]methanol (672 mg, 1.71 mmol) in CH2Cl2 (50 ml) and the mixture was stirred at room temperature for 1 h under N2, during which period the solid dissolved and then precipitated. The reaction mixture was concentrated under reduced pressure and then azeotroped with toluene (2×50 ml) and used without further purification. A portion of the crude chloromethyltriazole (125 mg, 0.30 mmol) and piperidine (0.30 ml, 3.0 mmol) in CH2Cl2 (6ml) were stirred at room temperature for 48 h under N2. The mixture was then concentrated under reduced pressure while dry loading onto silica and purified by column chromatography on silica using 2% MeOH/CH2Cl2 containing 1% NH3 solution as eluent to yield the desired phthalazine (126 mg, 90%), which was then recrystallised CH2Cl2/iso-hexanes. 1H NMR (360 MHz, CDCl3) δ 8.67 (1H, d, J=8.0 Hz), 8.14 (1H, d, J=8.0 Hz), 7.93 (1H, t, J=8.0 Hz), 7.75 (1H, d, J=8.0 Hz), 6.94 (1H, s), 5.77 (2H, s), 4.12 (3H, broad s), 3.70-3.60 (2H, m), 2.59 (3H, s), 2.40-2.30 (4H, m), 1.75-1.33 (6H, m).

1. dissolutiondissolved
2. customprecipitated
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. customazeotroped with toluene (2×50 ml)
5. customused without further purification
6. concentrationThe mixture was then concentrated under reduced pressure
7. customwhile dry loading onto silica
8. custompurified by column chromatography on silica using 2% MeOH/CH2Cl2 containing 1% NH3 solution as eluent