反应详情

To the suspension of the triethylamine salt of 3-[7-(aminomethyl)-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-[(cyclopropylmethyl)amino]-4-hydroxyquinolin-2(1H)-one (85.26 mg, 0.16 mmol) in N,N-dimethylformamide (1.6 mL) was added triethylamine (48 □L, 0.34 mmol) and then methanesulfonyl chloride (13.3 □L, 0.17 mmol) at room temperature. The solution was stirred at room temperature for 20 minutes and concentrated in vacuo. The residue purified by reverse phase chromatography, eluting with 20% to 95% acetonitrile/0.1% trifluoroacetic acid in water to give N-[(3-{1-[(cyclopropylmethyl)amino]-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl}-1,1-dioxido-4H-thieno[2,3-e][1,2,4]thiadiazin-7-yl)methyl]methanesulfonamide (compound II) (39.86 mg, 49%). MS (ESI+) m/z 524 (M+H)+. NMR (300 MHz, DMSO-d6) δ 0.15 (m, 2 H) 0.42 (m, 2 H) 1.01 (m, 1 H) 2.84 (d, J=7.35 Hz, 2 H) 2.99 (s, 3 H) 4.29 (d, J=6.25 Hz, 2 H) 6.37 (br s, 1 H) 7.41 (m, 2 H) 7.75 (t, J=6.25 Hz, 1 H) 7.87 (m, 1 H) 8.08 (d, J=8.09 Hz, 1 H) 8.16 (m, 1 H) 14.46 (m, 1 H).

1. customat room temperature
2. concentrationconcentrated in vacuo
3. customThe residue purified by reverse phase chromatography
4. washeluting with 20% to 95% acetonitrile/0.1% trifluoroacetic acid in water