反应详情

N6-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N2-(5-isopropoxy-1H-pyrazol-3-yl)-3-nitropyridine-2,6-diamine (Intermediate 20, 0.5 g) was dissolved into ethanol (20 mL) with Pd—C (60 mg) and a hydrogen inlet. The mixture was stirred at room temperature until no starting material was detected with TLC or LCMS. Formamidine acetate (0.5 g) was added to the filtrate after the filtration of resulting mixture. The mixture was stirred at 85° C. for 4 hours. Ethyl acetate (40 mL) was added into the resulting mixture, and brine (10 mL×3) was used to wash the organic layer. The organic layer was dried and concentrated. The resulting residue was separated by silica gel column (Ethyl acetate/MeOH) to afford 0.29 g of the title compound. MS (electrospray): 383 (M+1) for C18H19FN8O. 1H NMR (300 MHz, CD3OD) δ ppm 8.75 (s, 2H) 8.35 (s, 1H) 7.80 (d, 1H) 6.80 (d, 1H) 6.30 (s, 1H) 5.30 (m, 1H) 4.70 (m, 1H) 1.55 (d, 3H) 1.35 (d, 6H).

1. filtrationafter the filtration
2. customof resulting mixture
3. stirringThe mixture was stirred at 85° C. for 4 hours
4. washto wash the organic layer
5. customThe organic layer was dried
6. concentrationconcentrated
7. customThe resulting residue was separated by silica gel column (Ethyl acetate/MeOH)