反应详情

3-(3,5-Dichloro-4-(4-methoxybenzyloxy)phenyl)-N-(4-hydroxybenzyl)-1,2,4-oxadiazole-5-carboxamide (compound G, 60 mg, 0.12 mmol), 4-fluoro-3-(trifluoromethyl)phenylboronic acid (50 mg, 0.24 mmol), Cu(OAc)2 (44 mg, 0.24 mmol) and 3A powdered molecular sieves (70 mg) were stirred in an open tube in dichloromethane (3 mL). Pyridine (57 mg, 0.72 mmol) was added and the dark green suspension stirred vigorously at room temperature in an open tube for 1 d. The molecular sieves were filtered, washed with dichloromethane and the filtrate concentrated in vacuo. The residue was dissolved in dichloromethane (3 mL) and trifluoroacetic acid (0.3 mL) was added. The dark solution was stirred at room temperature for 5 h, then methanol (1 mL) was added and the solution concentrated in vacuo. The residue was purified by preparative HPLC providing the title compound (46 mg, 0.085 mmol, 71%). 1H NMR δ (ppm) (DMSO-d6): 4.53 (2 H, d, J=6.20 Hz), 7.06-7.13 (2 H, m), 7.36-7.48 (4 H, m), 7.53-7.60 (1 H, m), 8.01 (2 H, s), 10.03 (1 H, t, J=6.20 Hz), 11.20 (1 H, s). LCMS (10 cm_esci_Bicarb_MeCN) tR 3.48 min; m/z 540/542/544 [M−H]−.

1. filtrationThe molecular sieves were filtered
2. washwashed with dichloromethane
3. concentrationthe filtrate concentrated in vacuo
4. dissolutionThe residue was dissolved in dichloromethane (3 mL)
5. additiontrifluoroacetic acid (0.3 mL) was added
6. stirringThe dark solution was stirred at room temperature for 5 h
7. additionmethanol (1 mL) was added
8. concentrationthe solution concentrated in vacuo
9. customThe residue was purified by preparative HPLC