反应详情

The product of Example 9, step 7 (0.18 g, 0.42 mmol), BOP (0.21 g, 0.47 mmol), triethylamine (0.25 mL, 1.80 mmol), and 2-amino-5-aminomethyl-6-methylpyridine dihydrochloride (Sanderson, P. E., et al. WO 97/01338 (1997)) (0.10 g, 0.48 mmol), were dissolved in DMF (10 mL) and stirred at ambient temperature for 2 hours. The reaction was concentrated in vacuo and the crude product purified by flash column chromatography (gradient elution: 10% to 15% methanol in DCM) giving an impure product that was dissolved in DCM, washed with saturated sodium bicarbonate, water, and brine, dried over sodium sulfate, and filtered. The evaporated filtrate then gave the title compound as a pale yellow solid (0.23 g, 99%). 1H NMR (300 MHz, CDCl3) δ 7.64 (m, 1H), 7.56 (m, 1H), 7.35 (m, 1OH), 7.11 (d, 1H, J=8.3 Hz), 6.94 (d, 1H, J=8.5 Hz), 6.22 (d, 1H, J=8.1 Hz), 5.60 (br t, 1H, J=5.3 Hz), 4.49 (s, 2H), 4.37 (br s, 2H), 4.19 (d, 2H, J=5.5 Hz), 3.56 (s, 2H), 2.34 (s, 3H), 2.23 (s, 3H), 2.22 (s, 3H). Mass spectrum (LCMS, ESI pos.) calc'd. for C30H32N4O4S: 545.2 (M+H). Found: 545.2.

1. concentrationThe reaction was concentrated in vacuo
2. customthe crude product purified by flash column chromatography (gradient elution: 10% to 15% methanol in DCM)
3. customgiving an impure product that
4. washwashed with saturated sodium bicarbonate, water, and brine
5. dry with materialdried over sodium sulfate
6. filtrationfiltered