反应详情

温度

200 °C

3-Bromo-1-(4-methylphenyl)piperazine-2,2-dimethylpropan-1-one (Example 37, step 1; 2.00 g, 5.92 mmol) was dissolved in N-methylpyrrolidinone (10 mL). N-Ethylpiperazine (1.50 mL, 11.8 mmol) was added. The reaction mixture was split into four batches and each was heated at 200° C. for 15 minutes in a Biotage Initiator microwave at high absorption. The reaction mixtures were combined and dissolved in DCM (300 mL), and washed with water (2×80 mL), brine (100 mL), dried (MgSO4) and then concentrated in vacuo. The residue was purified by reverse phase column chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-30%). The resulting residue was dissolved in DCM (100 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo, to give a colourless oil which was recrystallised from heptane to give 1-{2,2-dimethyl-3-[4-(4-methylphenyl)piperazin-1-yl]-3-oxopropyl}-4-ethylpiperazine (1.19 g, 48%) as a white solid.

1. customThe reaction mixture was split into four batches
2. customThe reaction mixtures
3. washwashed with water (2×80 mL), brine (100 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. customThe residue was purified by reverse phase column chromatography (gradient
7. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
8. dissolutionThe resulting residue was dissolved in DCM (100 mL)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give a colourless oil which
12. customwas recrystallised from heptane