反应详情

温度

0 °C

Combine 10-thioxo-9,10-dihydro-4H-3-thia-1,4,9-triaza-benzo[f]azulene-2-carboxylic acid ethyl ester (3.59 g, 11.76 mmol) in 25 mL CH2Cl2 and add methyl trifluoromethanesulfonate (2.41 g, 14.7 mmol) dropwise at 0° C., stir at 0° C. for half hour, and warm to RT. After 2 h, concentrate the reaction mixture under reduced pressure, mix with (S)-2-(2-methoxy-ethyl)-piperazine (0.1.47 g, 10.2 mmol) in 20 mL pyridine and heat to 100° C. After 4 hours, cool the reaction to RT, and concentrate to a residue. Purification by flash chromatography (twice) on silica gel using a gradient (100% CH2Cl2 to 100% mixed solvent of (CH2Cl2: 2N NH3/MeOH=20:1)) over 55 min. gives the title compound: mass spectrum (electrospray) (m/e): C20H25N5O3S, Calc. Mass (M+1): 416.1756, Found: 416.1748. 1H NMR (400 MHz, CDCl3): δ 7.05-6.98 (m, 2H), 6.91-6.85 (m, 1H), 6.65-6.62 (m, 1H), 5.51 (br, 1H), 4.40 (q, 2H, J=7.5 Hz). 4.10 (br, 2H), 3.51 (t, 2H, J=6.0 Hz), 3.32 (s, 3H), 3.30-3.00 (m, 4H), 2.79-2.72 (m, 1H), 1.79-1.66 (m, 2H), 1.38 (t, 3H, J=7.5 Hz).

1. temperaturewarm to RT
2. waitAfter 2 h
3. concentrationconcentrate the reaction mixture under reduced pressure
4. temperatureheat to 100° C
5. waitAfter 4 hours
6. temperaturecool
7. customthe reaction to RT
8. concentrationconcentrate to a residue
9. customPurification by flash chromatography (twice) on silica gel using
10. additiona gradient (100% CH2Cl2 to 100% mixed solvent of (CH2Cl2: 2N NH3/MeOH=20:1)) over 55 min.