反应详情

Sodium hydride (34. mg; 0.78 mmol; 2.0 eq.) was added in one portion to a solution of 6-(3,5-Difluoro-phenyl)-2H-pyridazin-3-one (106 mg; 0.51 mmol; 1.3 eq.) in DMF (3 mL). After 10 min a solution of tert-butyl 5-(bromomethyl)-3-{1-[4-(methoxycarbonyl)phenyl]-1H-1,2,3-triazol-4-yl}-1H-indazole-1-carboxylate (392 mg; 0.38 mmol; 1.0 eq.) in DMF (3 mL) was added dropwise over 2 min and the reaction solution stirred for 4 h at RT. The reaction mixture was then poured into saturated solution of NaHCO3 and extracted with EtOAc. Combined organic phases were dried over magnesium sulfate, filtered and concentrated to give a yellow solid. This solid was redissolved in NaOH (5N, 0.5 mL) and DMSO (2 mL) and heated in MW for 10 min at 80° C. Reaction mixture was poured in a saturated solution of NaHCO3 and washed with EtOAc. The basic aqueous phase was acidified to pH 1 with 1N HCl and extracted with EtOAc. Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated to give the title compound as a yellow solid (218 mg, 100%). 1H NMR (300 MHz, DMSO-d6) δ 13.43 (s, 1H), 9.44 (s, 1H), 8.47 (s, 1H), 8.29-8.09 (m, 6H), 7.68 (d, J=7.2 Hz, 2H), 7.63-7.47 (m, 2H), 7.40-7.30 (m, 1H), 7.14 (d, J=9.8 Hz, 1H), 5.52 (s, 2H). HPLC (Condition A): Rt 3.87 min (purity 52.8%). MS (ESI+): 526.2, MS (ESI−): 524.2.

1. extractionextracted with EtOAc
2. dry with materialCombined organic phases were dried over magnesium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. customto give a yellow solid
6. customReaction mixture
7. washwashed with EtOAc
8. extractionextracted with EtOAc
9. washCombined organic phases were washed with brine
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated