Methanol → 3-chloro-6-(4-methoxyphenyl)-9H-pyrido[2,3-b]indole

At room temperature and under inert atmosphere, 1.0 M TBAF in THF (1.9 mL, 5 equiv.) was added a solution of 9-benzenesulfonyl-3-chloro-6-(4-methoxyphenyl)-9H-pyrido[2,3-b]indole (26) (169 mg, 0.376 mmol) in anhydrous THF (17 mL). The solution was refluxed for 2 h. The resulting mixture was then cautiously quenched at 0° C. with H2O. The mixture was extracted with EtOAc (3×10 mL). The resulting organic layers were dried over MgSO4, filtered, and solvents were removed under reduced pressure. The crude product was purified by flash chromatography (CH2Cl2/EtOAc 9:1) to afford R277 in 85% yield as a yellow solid; mp>220° C. (MeOH); IR: 3109, 3035, 2935, 2848, 1630, 1603, 1578, 1483, 1232, 1090, 1033, 800, 778, 700 cm−1; 1H-NMR (300 MHz, DMSO-d6): δ 12.02 (bs, 1H), 8.74 (d, 1H, J=2.4 Hz), 8.49 (d, 1H, J=1.8 Hz), 8.42 (d, 1H, J=2.4 Hz), 7.76 (dd, 1H, J=1.8, 8.6 Hz), 7.55 (d, 1H, J=8.5 Hz), 7.06 (d, 1H, J=8.7 Hz), 3.81 (s, 3H); 13C-NMR (75 MHz, DMSO-d6): δ 158.4 (C), 150.7 (C), 144.1 (CH), 138.8 (C), 133.2 (C), 132.1 (C), 128.3 (CH), 127.7 (2 CH), 126.2 (CH), 121.7 (C), 120.2 (C), 119.3 (CH), 126.6 (C), 114.4 (2 CH), 111.8 (CH), 55.2 (CH3); MS (ESI) m/z 309.1 [M+H]+; HRMS (EI): Calcd for C18H13ClN2O: 308.0716. Found: 308.0714.

1. temperatureThe solution was refluxed for 2 h
2. customThe resulting mixture was then cautiously quenched at 0° C. with H2O
3. extractionThe mixture was extracted with EtOAc (3×10 mL)
4. dry with materialThe resulting organic layers were dried over MgSO4
5. filtrationfiltered
6. customsolvents were removed under reduced pressure
7. customThe crude product was purified by flash chromatography (CH2Cl2/EtOAc 9:1)
8. customto afford R277 in 85% yield as a yellow solid

ORD record

ord-3c2efe11dc1e4b878f9b6bb9d12aa64a

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895744B2