反应详情

Add sodium triacetoxyborohydride (0.15 g, 0.71 mmol) and aqueous formaldehyde (37% w/w, 0.05 mL, 0.62 mmol) to a solution of (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-isopropyl-4H-3-thia-4,9-diaza-benzo[f]azulene (0.18 g, 0.47 mmol) in dichloroethane (12 mL) and stir. After 5 hours, dilute with a saturated aqueous solution of sodium bicarbonate, and separate the layers. Extract the aqueous layer with dichloromethane (3×), combine organics, and dry (sodium sulfate), filter, and concentrate under reduced pressure to an oil (0.24 g). Purify the oil by flash chromatography, eluting with a gradient of a 5% solution of 2M ammonia in methanol, in dichloromethane (0-100% over 30 minutes), and then with a 5% solution of 2M ammonia in methanol, in dichloromethane to give the title compound (0.14 g, 74%): mass spectrum (APCI, m/e): 399 (M+1); NMR (1H, 300 MHz, DMSO-d6) δ 7.63 (s, 1H), 6.79 (m, 3H), 6.66 (m, 1H), 6.30 (s, 1H), 3.70 (m, 2H), 3.35-3.28 (m, 2H), 3.20 (s, 3H), 2.99-2.88 (m, 2H), 2.80-2.60 (m, 2H), 2.29-2.05 (m, 5H), 1.66 (m, 2H), 1.17 (d, 6H, J=7.5 Hz).

1. customseparate the layers
2. extractionExtract the aqueous layer with dichloromethane (3×)
3. dry with materialdry (sodium sulfate)
4. filtrationfilter
5. concentrationconcentrate under reduced pressure to an oil (0.24 g)
6. customPurify the oil by flash chromatography
7. washeluting with a gradient of a 5% solution of 2M ammonia in methanol, in dichloromethane (0-100% over 30 minutes)