反应详情

To a solution of (S)-(tetrahydrofuran-2-yl-)-methanol (30.6 mg) in dry DMF (1 mL) NaH (12 mg, 60% dispersion in mineral oil) was added, and the mixture was stirred at room temperature for 20 minutes under nitrogen. To this mixture 6-chloro-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-chloro-5-fluoro-phenyl)-1H-benzoimidazol-2-yl]-amide (44.0 mg) was added, and the mixture was warmed to 80° C. The reaction was monitored by LCMS until substantially complete. Then, 10 mL of water was added and the reaction mixture was stirred for 10 minutes. The reaction was then filtered through a fine fritted funnel and the crude product was washed with water. After air drying, the product 6-[(S)-1-(tetrahydro-furan-2-yl)methoxy]-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-chloro-5-fluoro-phenyl)-1H-benzoimidazol-2-yl]-amide (24.8 mg) was purified by column chromatography (prepacked silica column) using 9:1 DCM and 2N ammonia in methanol. LCMS (m/z): 507.9. 1H NMR (400 MHz, CDCl3) δ 11.23 (1H, br. s.) 10.25-10.73 (1H, m) 8.40 (1H, s) 7.74 (2H, d) 7.38-7.44 (2H, m) 7.19-7.25 (2H, m) 7.04 (1H, dt) 6.83-6.89 (1H, m) 4.24-4.42 (3H, m) 3.82-4.03 (2H, m) 1.91-2.17 (2H, m) 1.67-1.82 (2H, m).

1. temperaturethe mixture was warmed to 80° C
2. stirringthe reaction mixture was stirred for 10 minutes
3. filtrationThe reaction was then filtered through a fine fritted funnel
4. washthe crude product was washed with water
5. customAfter air drying
6. customthe product 6-[(S)-1-(tetrahydro-furan-2-yl)methoxy]-imidazo[1,2-b]pyridazine-2-carboxylic acid [5-(3-chloro-5-fluoro-phenyl)-1H-benzoimidazol-2-yl]-amide (24.8 mg) was purified by column chromatography (prepacked silica column)