反应详情

To a solution of 21C (0.75 g, 4.01 mmol), 1-cyclobutylpiperazine, 2HCl (0.854 g, 4.01 mmol) and N-Ethyldiisopropylamine (2.79 mL, 16.03 mmol) in 20 ml of DMF at RT was added in portions HATU (1.523 g, 4.01 mmol). This was stirred for 60 min. then concentrated. The reaction was partitioned between EtOAc and 1 N HCl. The aq. layer was extracted 3× with EtOAc then made basic with 2 N NaOH. The aq. layer was extracted 3× with EtOAc and the combined organic layers were washed with brine then dried over MgSO4, filtered and concentrated. Purification was performed using a gradient of 0% to 10% MeOH in DCM. A second purification was necessary using first 100% EtOAc then 2-5% MeOH in DCM providing 0.853 g of 21D (68.8% yield).

1. concentrationthen concentrated
2. customThe reaction was partitioned between EtOAc and 1 N HCl
3. extractionThe aq. layer was extracted 3× with EtOAc
4. extractionThe aq. layer was extracted 3× with EtOAc
5. washthe combined organic layers were washed with brine
6. dry with materialthen dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification
10. customA second purification