反应详情

To a solution of 7-{1-[1-hydroxymethyl-4-(7-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-isoquinolin-3-yl}-4,7-diaza-spiro[2.5]octane-4-carboxylic acid tert-butyl ester (500 mg, 0.842 mmol) in 1,2-dichloroethane (5 mL) was added TFA (1.44 g, 0.973 mL, 12.7 mmol) under argon at 0° C. The reaction mixture was stirred for 1 h under argon at 0° C. after which additional TFA (0.768 g, 0.52 mL, 6.74 mmol) was added. Stirring was continued for 1.5 h at 0° C. The reaction mixture was evaporated to dryness at reduced pressure and the crude product was crystallised from MeOH to afford the title compound as a red solid (TFA salt) as a dark red solid. 1H-NMR (400 MHz, DMSO-d6): 12.01 (d, 1H), 9.06 (bs, 2H), 8.11 (d, 1H), 7.71-7.66 (m, 2H), 7.51 (t, 1H), 7.27 (s, 1H), 7.14 (t, 1H), 6.77 (d, 1H), 6.45-6.39 (m, 2H), 5.92 (d, 1H), 5.00 (d, 2H), 3.84-3.54 (m, 6H), 2.39 (s, 3H), 0.96-0.67 (m, 4H). LCMS: [M+1]+=493.7, Rt(1)=1.84 min.

1. additionwas added
2. customThe reaction mixture was evaporated to dryness at reduced pressure
3. customthe crude product was crystallised from MeOH