反应详情

trans-4-(1-Methyl-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-ylmethyl)-cyclohexanecarboxylic acid (1.0 g, 3.2 mmol), DIPEA (560 μL, 3.2 mmol), HATU (1.2 g, 0.32 mmol) were dissolved in 20 ml of DMF. The mixture was stirred at room temperature for 2 hours and then 14 ml of the solution were transferred in a different flask. To this solution Boc-piperazine (411 mg, 2.2 mmol) was added and the mixture was stirred at room temperature for 18 hours. The solvent was removed under reduced pressure and the residue dissolved in DCM and washed with 0.4 M solution of Na2CO3. The organic phase was separated and the solvent removed under reduced pressure to give 900 mg of crude boc protected intermediate. The compound was dissolved in 10 ml of DCM, 255 μL of H2SO4 were added and the mixture was left stirring at room temperature for 18 hours. The solution was washed with a solution of NaOH (10% W/W), the organic phase was separated and concentrated under reduced pressure to give 570 mg (yield 80%) of the titled compound.

1. stirringthe mixture was stirred at room temperature for 18 hours
2. customThe solvent was removed under reduced pressure
3. dissolutionthe residue dissolved in DCM
4. washwashed with 0.4 M solution of Na2CO3
5. customThe organic phase was separated
6. customthe solvent removed under reduced pressure
7. customto give 900 mg of crude boc protected intermediate
8. waitthe mixture was left
9. stirringstirring at room temperature for 18 hours
10. washThe solution was washed with a solution of NaOH (10% W/W)
11. customthe organic phase was separated
12. concentrationconcentrated under reduced pressure