反应详情

To a DCM (10 ml) solution of (S)-3-(aminomethyl)-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,6-diamine (Example 3; 0.45 g, 1.17 mmol) and HBTU (0.44 g, 1.17 mmol) cooled at 0° C. was added a solution of (R)-5-oxopyrrolidine-2-carboxylic acid (0.15 g, 1.17 mmol) in DMF (5 ml), followed by the addition of DIEA (0.14 g, 1.17 mmol). The reaction was then stirred at room temperature for 1 hour and quenched with 20 ml aqueous NaHCO3, and extracted with DCM (2×30 ml). The combined organic fractions were dried over Na2SO4, filtered, and then concentrated. The resulting oil was purified by column chromatography (DCM-MeOH=20:1) to give the title compound (0.25 g, 43%). 1H NMR (400 MHz, CD3OD) δ 7.37-7.34 (m, 2H), 7.14 (d, J=10.9 Hz, 1H), 7.02-6.97 (m, 2H), 5.80-5.65 (br s, 1H), 5.07 (br s, 1H), 4.33-4.16 (m, 3H), 2.46-2.22 (m, 3H), 2.05-1.98 (m, 1H), 1.88-1.81 (m, 1H), 1.51 (d, J=6.8 Hz, 3H), 0.93-0.92 (m, 2H), 0.66-0.62 (m, 2H). MS: Calcd.: 495. Found: [M+H]+ 496.

1. customquenched with 20 ml aqueous NaHCO3
2. extractionextracted with DCM (2×30 ml)
3. dry with materialThe combined organic fractions were dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe resulting oil was purified by column chromatography (DCM-MeOH=20:1)