反应详情

温度

100 °C

1-(5-Bromo-pyridin-2-yl)-cyclopropanecarboxylic acid amide (120 mg), Na2CO3 (443 mg), and Pd(PPh3)4 (12 mg) were added to a solution of (S)-4-(2-hydroxy-2-methylpropyl)-4-phenyl-1-{(S)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}tetrahydro-pyrimidin-2(1H)-one (200 mg; for preparation see WO 2009061498) in ethanol (6 mL), toluene (8 mL), and H2O (4 mL) at room temperature. The resulting mixture was stirred at 100° C. for 2 h under N2 atmosphere. After cooling to room temperature, the mixture was concentrated, diluted with H2O (30 mL), and extracted with ethyl acetate (3×50 mL). The combined organic layers were concentrated to afford an oil which was purified by preparative HPLC to give the title compound. Yield: 124 mg (58% of theory); LC (method 4): tR=0.98 min; Mass spectrum (ESI+): m/z=513 [M+H]+; 1H NMR (CDCl3, 400 MHz) δ 0.69 (s, 3H), 1.29 (m, 2H), 1.31 (m, 3H), 1.50 (d, 3H), 1.79 (m, 2H), 1.98-2.07 (m, 3H), 2.12-2.22 (m, 3H), 2.70-2.83 (m, 1H), 4.55 (s, 1H), 5.80-5.62 (m, 2H), 7.21 (m, 3H), 7.28 (m, 1H), 7.33 (m, 4H), 7.70 (m, 2H), 7.78 (m, 1H) 8.69 (s, 1H).

1. temperatureAfter cooling to room temperature
2. concentrationthe mixture was concentrated
3. additiondiluted with H2O (30 mL)
4. extractionextracted with ethyl acetate (3×50 mL)
5. concentrationThe combined organic layers were concentrated
6. customto afford an oil which
7. customwas purified by preparative HPLC