反应详情

Combine (S)-10-[3-(2-methoxyethyl)-piperazin-1-yl]-2-cyclopentyl-4H-3-thia-1,4,9-triazabenzo[f]azulene (0.364 g, 0.884 mmol), formaldehyde (93 μL, 1.15 mmol, 37%), and sodium triacetoxyborohydride (0.281 g, 1.33 mmol) in dichloroethane (15 mL) and stir at room temperature for 4 hours. Dilute the mixture with saturated aqueous sodium bicarbonate and extract three times with dichloromethane. Combine the organic layers, dry over sodium sulfate and concentrate under reduced pressure to give a solid residue. Purify by flash chromatography, eluting with a step gradient starting with dichloromethane going to 6% 2N ammonia-methanol in dichloromethane, to obtain the free base of the title compound (0.342 g; 0.804 mmol, 91%) as a yellow oil: mass spectrum (APCI): m/z=386.4 (M+1). Isolate the clean product as the corresponding dihydrochloride in the following manner: dissolve the yellow foam in ethanol (5 mL) and add a solution of about 5 equivalents of hydrochloric acid in ethanol (5 mL); then remove the solvent under vacuum: Exact Mass, Calc: 426.2328; Found: 426.2329.

1. extractionextract three times with dichloromethane
2. dry with materialdry over sodium sulfate
3. concentrationconcentrate under reduced pressure
4. customto give a solid residue
5. customPurify by flash chromatography
6. washeluting with a step gradient