反应详情

温度

150 °C

A suspension of 1-(6-(3-methylisoxazol-5-yl)pyridazin-3-yl)hydrazine hydrochloride (200 mg, 879 μmol) and methyl 2,2-difluoro-2-(quinolin-6-yl)acetate (208 mg, 879 μmol) in 5 M HCl (1 mL) was appropriately sealed and heated to 150° C. with microwaves for 4 h. The reaction was then quenched by a dropwise into cold 5 M NaOH (2 mL) and aqueous extracted with CHCl3/IPA (25 mL). The organic phase was then dried over MgSO4, concentrated, and purified with silica (40 g) eluting with 1>5% 2 M NH3 in MeOH/DCM. The product was then further purified on RP-HPLC eluting with water/ACN (0.1% TFA). Combined fractions concentrated, dissolved in DCM (5 mL) and MeOH (5 mL), then stirred with Si-Carbonate (0.5 g; 35 mmol) for 1 h. Si-Carbonate removed by filtration and filtrated concentrated with <0.5 mL remaining with product isolated by trituration. MS (ESI pos. ion) m/z: 379 (MH+). Calc'd exact mass for C19H12F2N6O: 378.

1. customwas appropriately sealed
2. customThe reaction was then quenched by a dropwise into cold 5 M NaOH (2 mL)
3. extractionaqueous extracted with CHCl3/IPA (25 mL)
4. dry with materialThe organic phase was then dried over MgSO4
5. concentrationconcentrated
6. custompurified with silica (40 g)
7. washeluting with 1>5% 2 M NH3 in MeOH/DCM
8. customThe product was then further purified on RP-HPLC
9. washeluting with water/ACN (0.1% TFA)
10. concentrationCombined fractions concentrated
11. dissolutiondissolved in DCM (5 mL)
12. customSi-Carbonate removed by filtration
13. filtrationfiltrated
14. concentrationconcentrated with <0.5 mL
15. customisolated by trituration