反应详情

The product of Example 9A (120 mg, 0.5 mmol) was coupled with the product of Example 20A (278 mg, 0.7 mmol) under the catalysis of by Pd2(dba)3 (Aldrich, 24 mg, 0.025 mmol) and (tBu3P)2 Pd (Strem Chemicals, 26 mg, 0.05 mmol) with CsF (Strem Chemicals, 152 mg, 1 mmol) in dioxane (10 ml) at 80° C. under N2 for 16 hours. After the reaction went to completion, it was diluted with EtOAc (50 mL) and washed with brine (2×10 mL). The organic solution was concentrated under vacuum and the residue was treated with TFA (1 mL) in CH2Cl2 (5 mL) at ambient temperature for 2 hours. It was then concentrated. The title product was purified by preparative HPLC (Xterra™, column, Xterra RP-18 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O (NH4HCO3, 0.1 M, pH=10) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (68 mg, 41%). 1H NMR (MeOH-D4, 300 MHz) 1.50-1.66 (m, 1H) 1.70-1.94 (m, 2H) 2.01-2.15 (m, 1H) 2.29-2.37 (m, 1H) 2.62 (s, 3H) 2.81-3.04 (m, 5H) 3.44-3.56 (m, 1H) 5.28-5.36 (m, 1H) 7.28 (d, J=9.2 Hz, 1H) 7.59 (d, J=8.8 Hz, 1H) 8.05 (dd, J=8.8, 1.4 Hz, 1H) 8.16 (d, J=9.2 Hz, 1H) 8.31 (s, 1H) ppm. MS (DCI/NH3) m/z 336 (M+H)+.

1. washwashed with brine (2×10 mL)
2. concentrationThe organic solution was concentrated under vacuum
3. additionthe residue was treated with TFA (1 mL) in CH2Cl2 (5 mL) at ambient temperature for 2 hours
4. concentrationIt was then concentrated
5. customThe title product was purified by preparative HPLC (Xterra™, column, Xterra RP-18 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O (NH4HCO3, 0.1 M, pH=10) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (68 mg, 41%)