反应详情

4-(6-Bromo-4-methyl-3-oxo-3,4-dihydro-pyrazin-2-ylamino)-N-(2-hydroxy-ethyl)-N-methyl-2-nitro-benzamide (4) (250 mg, 0.59 mmol, 1.0 equiv), 4,5,6,7-Tetrahydro-benzo[b]thiophene-2-carboxylic acid[2-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-amide (257 mg, 0.65 mmol) and tetrakis(triphenylphosphine)palladium (68 mg, 0.06 mmol) are dissolved in 1,4-dioxane (2.0 mL) and sodium carbonate (1N, 1.0 mL) and heated in a microwave glass reactor for 6 minutes at 140° C. Once completed the reaction is transferred to a seperatory funnel with ethyl acetate (50 mL) and washed with saturated sodium bicarbonate (1×100 mL), then washed with saturated sodium chloride (1×100 mL) and dried over sodium sulfate. The solution is then filtered and concentrated under reduced pressure. The resulting residue is then triturated with DCM and hexane to give 4,5,6,7-tetrahydro-benzo[b]thiophene-2-carboxylic acid [3-(6-{4-[(2-hydroxy-ethyl)-methyl-carbamoyl]-3-nitro-phenylamino}-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl)-2-methyl-phenyl]-amide (5) as a light yellow solid (225 mg).

1. washwashed with saturated sodium bicarbonate (1×100 mL)
2. washwashed with saturated sodium chloride (1×100 mL)
3. dry with materialdried over sodium sulfate
4. filtrationThe solution is then filtered
5. concentrationconcentrated under reduced pressure
6. customThe resulting residue is then triturated with DCM and hexane