反应详情

To toluene-4-sulfonic acid 3-cyclopentyl-7-(2-fluorophenyl)-4-methylpyrazolo[1,5-d][1,2,4]triazin-2-yl ester (Example 3, step c; 230 mg, 0.494 mmol) and (2-methyl-2H-[1,2,4]triazol-3-yl)methanol (67 mg, 1.2 molar eq; prepared as described in EP-A-170073) in DMF (10 ml) was added sodium hydride (22 mg of a 60% dispersion in mineral oil; 1.2 molar eq) and the mixture was stirred at room temperature for 1 h. Water (90 ml) was added then the solution was extracted with diethyl ether (4×50 ml). The combined ether layers were washed with brine (1×100 ml), dried (Na2SO4), the solvent was removed in vacuo and the residue was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane. 3-Cyclopentyl-7-(2-fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine was isolated as a gum, which solidified upon trituration under diethyl ether/isohexane (77 mg, mp=123° C.). 1H NMR (360 MHz, CDCl3) δ 1.60-1.98 (8H, m), 2.88 (3H, s), 3.42 (1H, m), 3.73 (3H, s), 5.44 (2H, s), 7.22-7.37 (2H, m), 7.56-7.71 (2H, m), 7.85 (1H, s); MS (ES+) m/e 408 [MH]+. Anal. Found C, 61.64; H, 5.31; N, 23.77%. C21H22FN7O requires C, 61.90; H, 5.44; N, 24.06%.

1. extractionthe solution was extracted with diethyl ether (4×50 ml)
2. washThe combined ether layers were washed with brine (1×100 ml)
3. dry with materialdried (Na2SO4)
4. customthe solvent was removed in vacuo
5. customthe residue was purified by flash chromatography on silica gel eluting with 0 to 50% ethyl acetate in dichloromethane