反应详情

A microwave vial was charged with 4-(4-bromo-2-fluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.29 mmol), 3-(dihydroxyboranyl)benzoic acid (0.29 mmol), PdCl2(dppf) (0.015 mmol), a solution of K2CO3 (0.733 mmol) in water (1 mL), and 1,4-dioxane (3 mL). The vial was purged with nitrogen, sealed, and irradiated in a microwave reactor for 30 min at 130° C. (pressure ˜3-4 bar). Analysis of the crude reaction by LCMS indicated ˜80% conversion to desired product. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in DMSO (3 mL), filtered through a syringe filter, and purified by reverse phase HPLC (10-90% acetonitrile/water+0.1% TFA). The appropriate product fractions were concentrated to remove a majority of the acetonitrile (product did not crash out). The mixture was adjusted to pH˜12 with 1N aq NaOH and partitioned with ethyl acetate. The aqueous layer was separated and adjusted to pH˜2 with 1N aq HCl, causing a gummy precipitate to form which was collected by filtration and dried to constant weight to provide the title product (39 mg, 0.087 mmol, 30% yield) as a tan solid. MS(ES)+ m/e 451.0 [M+H]+.

1. customThe vial was purged with nitrogen
2. customsealed
3. customirradiated in a microwave reactor for 30 min at 130° C. (pressure ˜3-4 bar)
4. customAnalysis of the crude reaction by LCMS