反应详情

To a suspension of 1-{trans-4-[8-amino-1-(1H-indol-2-yl)imidazo[1,5-a]pyrazin-3-yl]cyclohexyl}methanamine (100.00 mg, 0.27 mmol), N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.0798 g, 0.416 mmol), N,N-diisopropylethylamine (0.097 mL, 0.55 mmol), 1-hydroxbenzotriaxole Hydrate (0.0425 g, 0.277 mmol), and DMF (600 uL) in DCM (5 mL) was added AcOH (24 uL). The mixture was stirred at rt for 3 h under an atmosphere of nitrogen then diluted with DCM (20 mL), washed with saturated NaHCO3 (aq) (2×25 mL) and brine (2×25 mL), and brine (2×25 mL), then dried over Na2SO4, filtered and concentrated in vacuo. The residue was chromatographed over silica gel eluting with DCM→2% 2M NH3 in MeOH/DCM to afford 0.02 g of the title compound. MS (ES+): m/z 403.31 [MH+]. 1H NMR (400 MHz, CDCl3): δ 1.12-1.31 (m, 3H), 1.79-1.86 (m, 2H), 1.94-1.97 (m, 2H), 2.02 (s, 3H), 2.04-2.09 (m, 2H), 2.91 (m, 1H), 3.20 (t, J=6.4 Hz, 2H), 5.51 (br, 1H), 5.66 (br, 2H), 6.79 (s, 1H), 7.10-7.16 (m, 2H), 7.20-7.25 (m, 2H), 7.43 (d, J=8.4 Hz, 1H), 7.44 (d, J=7.6 Hz, 1H), 9.07 (br, 1H).

1. washwashed with saturated NaHCO3 (aq) (2×25 mL) and brine (2×25 mL), and brine (2×25 mL)
2. dry with materialdried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe residue was chromatographed over silica gel eluting with DCM→2% 2M NH3 in MeOH/DCM