反应详情

To a stirred sol. of the compound D8 (2.75 g, 4.30 mmol) in CH2Cl2 (21.5 mL) were added EDC.HCl (2.06 g, 10.75 mmol), HOBt (0.789 g, 5.16 mmol), DMAP (13 mg, 0.108 mmol), and DIPEA (3.378 mL, 19.3 mmol). After 15 min cyclopropyl-(3-methoxy-2-methylbenzyl)amine (prepared by reductive amination from 3-methoxy-2-methylbenzaldehyde, Comins, D. L.; Brown, J. D., J. Org. Chem., 1989, 54, 3730 and cyclopropylamine, 2.47 g, 12.9 mmol) was added, and stirring was continued over 7 days. Three times were added cyclopropyl-(3-methoxy-2-methylbenzyl)amine (823 mg, 4.30 mmol), and HOBt (290 mg, 2.15 mmol), and once was added DIPEA (3.38 mL, 19.3 mmol). The reaction mixture was partitioned between aq. 1M HCl and CH2Cl2, and the phases were separated. The org. layer was washed with aq. sat. NaHCO3, dried over MgSO4, filtered, and the solvents were removed in vacuo. Purification of the residue by FC (heptane/EtOAc 7/3) yielded an impure product, which was purified again by HPLC. The title compound (1.16 g, 33%) was obtained as a yellow oil. LC-MS: tR=1.26 min, ES+: 813.59.

1. customThe reaction mixture was partitioned between aq. 1M HCl and CH2Cl2
2. customthe phases were separated
3. washlayer was washed with aq. sat. NaHCO3
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customthe solvents were removed in vacuo
7. customPurification of the residue by FC (heptane/EtOAc 7/3)
8. customyielded an impure product, which
9. customwas purified again by HPLC