HOAt → N-(2-amino-4-(trifluoromethoxy)phenyl)-3-(3-((((3 aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanamide

Participants

Reaction Steps

To a solution of 3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanoic acid (1.2 g, 2.91 mmol), HATU (2.17 g, 5.83 mmol) and HOAT (0.91 g, 5.83 mmol) in DCM (17 mL) were added 4-(trifluoromethoxy)benzene-1,2-diamine (1.1 g, 5.83 mmol) and TEA (2.05 mL, 14.56 mmol). The mixture was stirred at rt overnight. The mixture was diluted with DCM (50 mL) and washed with water (15 mL×3) and brine (30 mL). The organic phase was dried over Na2SO4, filtered and concentrated. The residue was purified by Combi-Flash (40 g silica gel, start EA:DCM:MeOH=10:10:0 to 10:10:8 by gradient, 40 mL/min, 50 min, 2.0 L total solvent volume) to afford the desired compound (1.0 g, yield: 60%) as a yellow solid. 1H NMR (500 MHz, MeOD): δH 8.29 (s, 1H), 8.25-8.24 (m, 1H), 7.20-7.13 (m, 1H), 6.95-6.85 (m, 0.4H), 6.73 (brs, 0.8H), 6.54 (d, J=7.5 Hz, 0.8H), 6.22 (d, J=2.0 Hz, 1H), 5.60-5.55 (m, 1H), 5.03-5.00 (m, 1H), 4.40-4.35 (m, 1H), 3.40-3.35 (m, 0.3H), 3.00-2.92 (m, 0.7H), 2.70-2.47 (m, 3H), 2.36-2.28 (m, 2H), 2.20-1.80 (m, 6H), 1.76-1.66 (m, 2H), 1.60 (s, 3H), 1.40 (s, 3H), 1.26-1.16 (m, 1H) ppm; ESI-MS (m/z): 621.3 [M+1]+.

Provenance & Evidence