反应详情

Using the method of Example 322, using (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-4H-3-thia-1,4,9-triaza-benzo[f]azulene-2-carboxylic acid ethyl ester (300 mg, 0.72 mmol), formaldehyde (37%, w/w, aq) (72.9 mg, 0.90 mmol) and sodium triacetoxyborohydride (228.9 mg, 1.08 mmol) gives 280 mg (yield 90%) of (5)-10-[3-(2-methoxy-ethyl)-4-methyl-piperazin-1-yl]-4H-3-thia-1,4,9-triaza-benzo[f]azulene-2-carboxylic acid ethyl ester: mass spectrum (electrospray) (m/e): 430.0 (M+1), 428.1 (M−1); 1H NMR (400 MHz, DMSO-d6): 8.50 (s, 1H), 6.91-6.80 (m, 3H), 6.69-6.67 (m, 1H), 4.30 (q, 2H, J=6.8 Hz), 3.83-3.81 (m, 2H), 3.32-3.30 (m, 2H), 3.13 (s, 3H), 3.12-3.06 (m, 1H), 2.81-2.70 (m, 2H), 2.22-2.13 (m, 5H), 1.83-1.75 (m, 1H), 1.53-1.46 (m,1H), 1.27 (t, 3H, J=7.2 Hz). The dihydrochloride is form by adding 5 eq of acetyl chloride (256.2 mg, 3.26 mmol) to the free base (280 mg, 0.65 mmol) in ethanol. Collect the precipitates via vacuum filtration to afford 300 mg of yellow solid of the title compound: mass spectrum (electrospray) (m/e): C21H27N5O3S.2HCl, Calc. Mass (M+1): 430.1913,