反应详情

温度

95 °C

A mixture of 4-(4-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine (1.01 g, 2.043 mmol), bis(pinacolato)diboron (1.556 g, 6.13 mmol), Pd2(dba)3 (0.094 g, 0.102 mmol), X-Phos (0.097 g, 0.204 mmol) and potassium acetate (0.602 g, 6.13 mmol) in 1,4-Dioxane (20 mL) in a 40 mL scintillation vial was heated for 1 hr at 95° C. When cooled the reaction contents were poured into 1N HCl (10 ml) and H2O (10 mL) mixture, swirled and then extracted with EtOAc, dried over MgSO4 and concentrated in-vacuo. The residue was dissolved in MeOH and the material was purified by reverse phase chromatography eluting with a gradient 30% CH3CN to 60% CH3CN over 10 minutes. The fractions containing clean desired compound were combined and concentrated in-vacuo to provide the desired product (196 mg, 0.427 mmol, 20.89% yield) as a clear oil after drying in a vacuum oven at 50° C. The oil was triturated to provide an analytically pure off-white powder (2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid (115 mg, 0.250 mmol, 12.26% yield). m/e: 459.2, 460.3 [M+H]+; 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.67 (d, J=8.08 Hz, 1H), 7.50 (br. s., 1H), 7.28 (t, J=7.83 Hz, 1H), 7.08 (d, J=2.27 Hz, 1H), 6.73 (d, J=8.08 Hz, 1H), 5.90 (s, 2H), 3.72-3.92 (m, 4H), 3.10-3.23 (m, 4H), 2.21-2.42 (m, 1H), 1.22-1.37 (m, 4H).

1. temperatureWhen cooled
2. customthe reaction contents
3. extractionextracted with EtOAc
4. dry with materialdried over MgSO4
5. concentrationconcentrated in-vacuo
6. dissolutionThe residue was dissolved in MeOH
7. customthe material was purified by reverse phase chromatography
8. washeluting with a gradient 30% CH3CN to 60% CH3CN over 10 minutes
9. additionThe fractions containing clean desired compound
10. concentrationconcentrated in-vacuo