反应详情

A solution of [(1S)-2,2-dimethyl-1-({(1S,4S)-5-[(5-phenyl-2-pyridinyl)carbonyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)propyl]amine (100 mg, 0.25 mmol), 5-fluoro-1H-indole-2-carboxylic acid (48 mg, 0.26 mmol), EDC (58 mg, 0.3 mmol), HOBt (7 mg, 0.05 mmol), NMM (77 mg, 0.76 mmol) in CH2Cl2 (3 mL) was stirred at room temperature for 2 h. The mixture was washed with 1N sodium hydroxide (2×3 mL), water (2×10 mL). The combined aqueous washes were extracted with CH2Cl2 (2×5 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered concentrated to give the crude product, which was purified by reverse phase HPLC. Concentration of the desired fractions containing product afforded the title compound (66 mg) as a pale yellow solid. LCMS (m/z): 554.3 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm: 0.90-1.10 (m, 9H), 1.80-2.15 (m, 2H), 3.45-4.20 (m, 4H), 4.60-5.55 (m, 3H), 6.90-7.60 (m, 10H), 7.80-8.10 (m, 2H), 8.55-8.90 (m, 1H), 9.20-9.55 (m, 1H)

1. washThe mixture was washed with 1N sodium hydroxide (2×3 mL), water (2×10 mL)
2. extractionThe combined aqueous washes were extracted with CH2Cl2 (2×5 mL)
3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customto give the crude product, which
7. customwas purified by reverse phase HPLC
8. additionConcentration of the desired fractions containing product