Pyridine → 4-(2-Fluorophenyl)-7-(methylsulfonamido)-9H-pyrido[3,4-b]indole-1-carboxamide

To a solution of 7-amino-4-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-1-carboxamide (25 mg, 0.078 mmol) in dichloromethane (2 mL) at rt was sequentially added methanesulfonyl chloride (22.35 mg, 0.195 mmol) and pyridine (0.016 mL, 0.195 mmol). The mixture was stirred at room temperature for 1 hr and then at 50° C. in a closed vial for 30 min. The mixture was concentrated. The residue was diluted with MeOH (1.5 mL) and subjected to prep. reverse phase HPLC purification. The correct fraction was concentrated under vacuum, basified with saturated NaHCO3 solution to pH 9, and extracted with ethyl acetate (3×30 mL). The combined extracts were washed with brine (25 mL) and dried over anhydrous MgSO4. Removal of solvent under vacuum provided the desired product (4.81 mg, 0.012 mmol, 15.00% yield) as a pale solid. LCMS (M+H)+=399.03. 1H NMR (500 MHz, DMSO-d6) δ: 11.85 (s, 1H), 10.03 (s, 1H), 8.30 (s, 1H), 8.23 (s, 1H), 7.77 (s, 1H), 7.75 (s, 1H), 7.67-7.63 (m, 2H), 7.50-7.43 (m, 2H), 7.19 (d, J=7.7 Hz, 1H), 6.92 (dd, J1=8.8 Hz, J2=2.2 Hz, 1H), 3.02 (s, 3H).

1. customat rt
2. waitat 50° C. in a closed vial for 30 min
3. concentrationThe mixture was concentrated
4. additionThe residue was diluted with MeOH (1.5 mL)
5. customphase HPLC purification
6. concentrationThe correct fraction was concentrated under vacuum
7. extractionextracted with ethyl acetate (3×30 mL)
8. washThe combined extracts were washed with brine (25 mL)
9. dry with materialdried over anhydrous MgSO4
10. customRemoval of solvent under vacuum

ORD-Eintrag

ord-08fc264d33314b05b5ccb598408cb97f

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08685969B2