反应详情

The carboxylic acid from Step D (60.0 mg, 0.188 mmol), amine from Step G (41.6 mg, 0.188 mmol), EDC hydrochloride (43.2 mg, 0.225 mmol), HOBT (30.4 mg, 0.225 mmol), and N,N-diisopropylethylamine (0.163 mL, 0.938 mmol) were stirred in dry, degassed DMF (1 mL) at 25° C. for 16 hours. The crude product was purified by preparative HPLC using a gradient of 5%-95% acetonitrile/0.1% TFA; 95%-5%/0.1% aqueous TFA over 15 min. The title compound was isolated after conversion to the HCl salt. MS (es) m+1=439. 1H-NMR (CD3OD): δ7.87 (d, 2H, J=7.8 Hz); 7.71 (d, 2H, J=8.5 Hz); 7.70 (t, 1H, J=7.8 Hz); 7.59 (t, 2H, J=7.7 Hz); 7.49 (s, 1H); 7.17 (d, 2H, J=8.0 Hz); 6.24 (bd, 1H, J=7.7 Hz); 4.64 (dd, 1H, J=12.3, 8.9 Hz); 3.74 (d, 1H, J=12.3 Hz), 3.28-3.57 (m, 4H).

1. customin dry
2. customdegassed DMF (1 mL) at 25° C. for 16 hours
3. customThe crude product was purified by preparative HPLC