反应详情

To a solution of (R)-tert-butyl 3-((8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinolin-2-yl)oxy)piperidine-1-carboxylate (117 mg, 0.25 mmol) in DCM (3.0 mL) at 0° C. was added TFA (0.5 mL, 6.73 mmol). The reaction was stirred at RT for 20 min. The solution was concentrated, the residue was dissolved in DCM and washed with a saturated aq. solution of NaHCO3. The aq. layer was extracted with DCM (2×). The combined organic layers were dried over MgSO4, filtered and concentrated. The residue was dissolved in DMSO (3.0 mL). Purification by rpHPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm, 5-95% 0.1% TFA/ACN in 0.1% TFA/water by volume over 10 min.), followed by drying in a Genevac Series II Evaporator afforded (R)-2-(2-(piperidin-3-yloxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one 2,2,2-trifluoroacetate (15.7 mg, 0.033 mmol, 13.0% yield) as an amorphous yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.63 (br. s., 1H), 8.76 (s, 1H), 8.80 (s, 1H), 8.34 (d, J=8.8 Hz, 1H), 7.96 (d, J=7.2 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.50 (t, J=7.6 Hz, 1H), 7.17 (d, J=2.0 Hz, 1H), 7.10 (d, J=8.8 Hz, 1H), 7.03 (br. s., 1H), 5.52 (br. s., 1H), 3.39-3.55 (m, 4H), 3.15 (br. s., 2H), 2.89 (t, J=6.7 Hz, 2H), 2.13-2.24 (m, 1H), 1.93-2.07 (m, 2H), 1.82-1.92 (m, 1 H). 19F NMR (376 MHz, DMSO-d6) δ ppm −74.47 (s, 3F). m/z (ESI, +ve ion) 363.0 (M+H)+.

1. concentrationThe solution was concentrated
2. dissolutionthe residue was dissolved in DCM
3. washwashed with a saturated aq. solution of NaHCO3
4. extractionThe aq. layer was extracted with DCM (2×)
5. dry with materialThe combined organic layers were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. dissolutionThe residue was dissolved in DMSO (3.0 mL)
9. customPurification by rpHPLC (Silicycle Silichrome XT C18 column; 30×150 mm, 5 μm, 5-95% 0.1% TFA/ACN in 0.1% TFA/water by volume over 10 min.)
10. dry with materialby drying in a Genevac Series II Evaporator