反应详情

To an nitrogene purged suspension of 2-morpholino-[1,2,4]triazolo[1,5-a]pyridin-7-amine hydrochloride (80 mg, 0.313 mmol) and N-ethyldiisoppropylamine (120 ul, 0.688 mmole) in dioxane (3 ml) is added trimethyl aluminium (2 M solution in toluene, 0.47 ml, 0.94 mmol). The resulting solution is stirred for ½ hour at room temperature. Then ethyl 4-(azetidine-1-carbonyl)-1-methyl-1H-pyrazole-5-carboxylate (75 mg, 0.313 mmol) in dioxane (0.7 ml) is added and the mixture is heated to reflux in a sealed vessel and stirred for 19 hours. Purification of the reaction mixture by chromatography on a 12 g RediSep silica cartridge (eluent dichloromethane+4% methanol) affords 4-(azetidine-1-carbonyl)-1-methyl-N-(2-morpholino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-1H-pyrazole-5-carboxamide (106 mg, 82.5%) as an off-white solid. mp.: 232-4° C. MS: m/z=411.3 (M+H+).

1. customTo an nitrogene purged
2. temperaturethe mixture is heated
3. temperatureto reflux in a sealed vessel
4. stirringstirred for 19 hours
5. customPurification of the reaction mixture by chromatography on a 12 g RediSep silica cartridge (eluent dichloromethane+4% methanol)