反应详情

温度

140 °C

Charge a microwave tube with 3′-chloro-4-(1,3-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.150 g, 0.490 mmoles), bis[(diphenylphosphanyl)methyl]-amine palladium (II) dichloride polymer bound (0.061 g, 0.049 mmoles, 0.1 eq), 4-(methoxycarbonyl)phenylboronic acid (0.176 g, 0.98 mmoles, 2 eq), sodium carbonate (0.192 g, 1.8 mmoles, 3.7 eq) and 3 ml of ethanol. Seal the reaction and heat under microwave conditions at 140° C. for 30 min. Cool down reaction and apply crude material to an SCX column prewashed with 10 ml methanol. Wash material with 10 ml of methanol, and release the product with 20 ml of a 2 N-ammonia/methanol solution. Purify the crude brown oil by reverse phase chromatography (28% isocratic acetonitrile/0.01 M ammonium bicarbonate in water, 80 ml/min., for 8 min., on a 30×75 mm, C18 Xterra column) to provide methyl 4-(3-(4-((1,3-dimethyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)pyrazin-2-yl)benzoate as a white solid (0.051 g, 26% yield, ES+(m/z) 407 [M+H]). Convert the purified material to the hydrochloride salt by stirring a solution of the free base (0.045 g, 0.294 mmoles) in acetonitrile (5 ml) at room temperature and add 1 N HCl in water (0.294 ml, 0.294 mmoles) to give a yellow solution. After 5 min., freeze the solution and lyophilize to give the title compound as a white solid (0.056 g, 100% yield, ES+(m/z) 407 [M+H]).

1. customSeal
2. customthe reaction
3. temperatureCool down reaction and apply crude material to an SCX column
4. customPurify the crude brown oil by reverse phase chromatography (28% isocratic acetonitrile/0.01 M ammonium bicarbonate in water, 80 ml/min.