反应详情

温度

130 °C

To a microwave vial was added dioxane (9 mL), water (0.900 mL), 2-carbamoylphenylboronic acid (148 mg, 0.900 mmol), methyl 2-chloro-5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoate (131 mg, 0.3 mmol), tribasic potassium phosphate (255 mg, 1.200 mmol), dicyclohexyl (2′,6′-dimethoxybiphenyl-2-yl)phosphine (S-Phos, 24.63 mg, 0.060 mmol), and palladium(II) acetate (13.47 mg, 0.060 mmol). The vial was capped, degassed, flushed with N2 and heated in the microwave for 13 minutes at 130° C. The reaction mixture was filtered and solvent removed under a stream of nitrogen. The crude product was then taken up in 4 mL of acetonitrile and purified using a Shimadzu preparative HPLC employing acetonitrile/water/trifluoroacetic acid where solvent A was 10% acetonitrile/90% water/0.1% trifluoroacetic acid and solvent B was 10% water/90% acetonitrile/0.1% trifluoroacetic acid with a Waters Sunfire 5 μm C18 19×150 mm column at a gradient of 20-100% B and a flow rate of 25 mL/min. over 20 minutes with a 10 minute hold. The solvent was removed giving 58.3 mgs (36% yield) of methyl 2′-carbamoyl-4-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)biphenyl-2-carboxylate as a yellow solid. The LC/MS data was obtained on a Shimadzu analytical LC/MICROMASS® Platform LC (ESI+) at 220 nm using the following set of conditions: PHENOMENEX® Luna 3 μm C18, 2×50 mm column, with a gradient of 0-100% B (B=90% HPLC grade acetonitrile/0.1% trifluoroacetic acid/10% HPLC grade water), (A=90% HPLC grade water/0.1% trifluoroacetic acid/10% HPLC grade acetonitrile), in 4 minutes with a 1 minute hold at a rate of 0.8 mL/minute. 1H NMR (400 MHz, THF-d8) δ ppm 2.93 (d, J=4.52 Hz, 3H), 3.62 (s, 3H), 6.35 (br. s., 2H), 7.09-7.15 (m, 1H), 7.22 (t, J=8.91 Hz, 2H), 7.31-7.43 (m, 3H), 7.52 (d, J=4.27 Hz, 1H), 7.58-7.71 (m, 3H), 7.81 (dd, J=8.03, 2.01 Hz, 1H), 8.01 (d, J=1.25 Hz, 1H), 8.09-8.20 (m, 3H). LCMS m/z 523.3 (M+H), Rt=3.051 min., 96% purity.

1. customThe vial was capped
2. customdegassed
3. customflushed with N2
4. filtrationThe reaction mixture was filtered
5. customsolvent removed under a stream of nitrogen
6. custompurified
7. customThe solvent was removed