反应详情

温度

100 °C

5-chloro-2-furan-2-yl-[1,2,4]triazolo[1,5-a]pyrimidin-7-ylamine (1 eq; see WO 99/43678 A1), cis-(octahydro-pyrido[1,2-a]pyrazin-7-yl)-methanol (1-2 eq), and CsF (1-2 eq) were dissolved in DMSO. The mixture was stirred at around 100° C. for 18 hours. The solution was then cooled to room temperature, filtered, and purified by preparative HPLC using aqueous CH3CN (buffered with 0.1% TFA) to give the desired compound as a white solid. Alternatively, for scale up synthesis, the DMSO solvent was removed and the crude product was chromatographed on silica gel column using 5-10% MeOH/CH2Cl2 as eluant to afford the desired product: 1H NMR (400 Hz, CD3OD) δ 7.69 (d, J=2.3 Hz, 1H), 7.10 (d, J=3.5 Hz, 1H), 6.61 (dd, J=3.5, 2.3 Hz, 1H), 5.73 (s, 1H), 4.32 (d, J=13.5 Hz, 1H), 4.24 (d, J=13.5 Hz, 1H), 3.82 (dd, J=10.5, 7.5 Hz, 1H), 3.74 (dd, J=10.5, 7.5 Hz, 1H), 3.10 (dt, J=12.5, 3.2 Hz, 1H), 2.94 (d, J=11.5 Hz, 1H), 2.79 (d, J=11.5 Hz, 1H), 2.67 (dd, J=13.0, 10.5 Hz, 1H), 2.21 (m, 2H), 1.96 (m, 1H), 1.85 (brd, 12.0 Hz, 2H), 1.60 (m, 1H), 1.47 (m, 2H). MS m/z: 370 [M+H]+.

1. temperatureThe solution was then cooled to room temperature
2. filtrationfiltered
3. custompurified by preparative HPLC