反应详情

To a solution of 3-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)cyclobutyl)propanoic acid (2.7 g, 4.33 mmol), 4-(trifluoromethoxy)benzene-1,2-diamine (1.23 g, 6.49 mmol), HATU (2.5 g, 6.49 mmol) and HOAT (0.88 g, 6.49 mmol) in DCM (30 mL) was added TEA (1.8 mL, 12.99 mmol). The mixture was stirred at rt for 2 h. The mixture was added DCM (70 mL) and washed with water (20 mL×2) and brine (50 mL). The organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by Combi-Flash (80 g silica gel, start EA:DCM:MeOH=10:10:0 to 10:10:2 by gradient, 60 mL/min, 40 min, 2.4 L total solvent volume) to afford to afford the desired compound (2.2 g, yield: 67% (two steps) as a brown solid. 1H NMR (500 MHz, MeOD): δH 8.21 (s, 1H), 7.28-7.12 (m, 3H), 6.73 (brs, 1H), 6.69 (brs, 1H), 6.56-6.52 (m, 2H), 6.42 (dd, J=8.0 and 2.5 Hz, 1H), 6.26 (d, J=1.5 Hz, 1H), 5.48 (d, J=6.0 Hz, 1H), 5.20-5.16 (m, 1H), 4.66 (s, 2H), 4.46-4.42 (m, 1H), 4.08-3.98 (m, 0.5H), 3.84 (s, 3H), 3.76 (s, 3H), 3.75-3.69 (m, 0.5H), 3.60-3.38 (m, 2H), 2.60-2.30 (m, 3H), 1.92-1.86 (m, 1H), 1.80-1.70 (m, 1H), 1.59 (d, J=3.5 Hz, 3H), 1.40 (s, 3H), 1.25 (t, J=7.5 Hz, 3H),), 1.00-0.80 (m, 2H) ppm; ESI-MS (m/z): 798.3 [M+1]+.

1. washwashed with water (20 mL×2) and brine (50 mL)
2. dry with materialThe organic phase was dried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated
5. customThe residue was purified by Combi-Flash (80 g silica gel, start EA:DCM:MeOH=10:10:0 to 10:10:2 by gradient, 60 mL/min, 40 min, 2.4 L total solvent volume)
6. customto afford