反应详情

A solution of (E)-3-(tert-butylamino)-5-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxaline-2-carbaldehyde oxime (308) (26.3 mg, 0.069 mmol) and 1-propanephosphonic acid cyclic anhydride (Alfa Aesar, Ward Hill, Mass.; 50 wt % solution in EtOAc; 0.16 mL, 0.28 mmol) in DMF (2.0 mL) was stirred at 100° C. for 3.5 h. The reaction mixture was then cooled to RT, diluted with saturated aq. NaHCO3 (30 mL), and extracted with 5% MeOH/DCM (2×30 mL). The combined extracts were sequentially washed with water (2×20 mL) and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was taken up in DMSO (2.0 mL) and purified by rpHPLC (Phenomenex Gemini C18 column (150×30 mm, 10 mm), 35 mL/min, 5-100% CH3CN/H2O+0.1% TFA). Product-containing fractions were combined and neutralized with saturated aq. NaHCO3 (30 mL). The resulting mixture was extracted with 5% MeOH/DCM (2×30 mL), and the combined extracts were dried over Na2SO4, filtered, and concentrated in vacuo to provide 3-(tert-butylamino)-5-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxaline-2-carbonitrile (8.9 mg, 0.025 mmol, 36% yield) as a red-orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.61 (1H, br. s.), 7.98 (1H, dd, J=7.4, 1.2 Hz), 7.73 (1H, dd, J=8.2, 1.2 Hz), 7.52 (1H, t, J=7.8 Hz), 7.12 (1H, d, J=2.3 Hz), 6.95 (1H, br. s.), 6.60 (1H, s), 3.42 (2H, td, J=6.8, 2.2 Hz), 2.84 (2H, t, J=6.8 Hz), 1.53 (9H, s). m/z (ESI, +ve) 361.1 (M+H)+.

1. extractionextracted with 5% MeOH/DCM (2×30 mL)
2. washThe combined extracts were sequentially washed with water (2×20 mL) and brine (20 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. custompurified by rpHPLC (Phenomenex Gemini C18 column (150×30 mm, 10 mm), 35 mL/min, 5-100% CH3CN/H2O+0.1% TFA)
7. extractionThe resulting mixture was extracted with 5% MeOH/DCM (2×30 mL)
8. dry with materialthe combined extracts were dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo