تفاعل #74542
ord-a56b2fb34d9b4a5b801b4d1e1d9caa42
معادلة التفاعل
المتفاعلات
الكواشف
المذيبات
ظروف التفاعل
المعالجة
- 1درجة الحرارةThe solution was cooled
- 2ترشيحfiltered
- 3ترشيحThe mixture was filtered
- 4تركيزconcentrated
- 5أخرىto remove most of the ethanol
- 6استخلاصThe resulting slurry was extracted with dichloromethane (3×)
- 7تجفيفdried over anhydrous magnesium sulfate
- 8ترشيحfiltered
- 9تركيزconcentrated
الإجراء التجريبي
To a solution of 5-chloro-N-(2,4-dimethoxybenzyl)-2-fluoro-4-{2-[3-nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-4-(trifluoromethyl)phenoxy}-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 867, 3.20 g, 4.00 mmol) in ethanol (200 mL) was added saturated aqueous ammonium chloride solution (50 mL) and iron (5.66 g, 101 mmol). The reaction solution was heated at 80° C. for 15 minutes. The solution was cooled, filtered and adjusted to pH=9 with saturated aqueous sodium bicarbonate solution. The mixture was filtered and then concentrated to remove most of the ethanol. The resulting slurry was extracted with dichloromethane (3×). The organic extracts were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated. This provided the aminopyrazole as a yellow foam. To this was added an HCl (g) saturated methanol solution (200 mL) and the mixture heated at 60° C. for two hours. The reaction solution was cooled, concentrated, and purified by automated flash column chromatography using a 0-10% methanol/dichloromethane gradient. Additional purification by prep HPLC provided the TFA salt. The resulting white solid was redissolved in a HCl (g) saturated methanol solution and concentrated (3×) in order to isolate the HCl salt of the title compound (1.20 g, 53%) as a white solid.