Methyl Isocyanate → 4-(5,7-difluoro-3-methyl-4-(6'-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]-1'(2'H)-yl)quinolin-2-yl)-N-methylpiperazine-1-carboxamide

Participants

Reaction Steps

1′-(5,7-difluoro-3-methyl-2-(piperazin-1-yl)quinolin-4-yl)-6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (50 mg, 0.093 mmol) was dissolved in DCM (5.0 mL), and treated with methylisocyanate (5.50 μL, 0.093 mmol) and the reaction was stirred at rt for 2.5 h. After this time the reaction was concentrated to dryness and the residue was purified using an SCX column (compound loaded in MeOH and using 2M ammonia in MeOH as eluent) to give 4-(5,7-difluoro-3-methyl-4-(6′-morpholino-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine]-1′(2′H)-yl)quinolin-2-yl)-N-methylpiperazine-1-carboxamide. 1H NMR (400 MHz, chloroform-d) δ ppm 7.55 (1H, d, J=2.3 Hz), 7.34 (1H, dt, J=9.8, 1.3 Hz), 6.75 (1H, ddd, J=11.8, 9.0, 2.4 Hz), 5.65 (1H, d, J=2.3 Hz), 4.69 (1H, q, J=4.2 Hz), 4.03-4.20 (2H, m), 3.80-3.97 (2H, m), 3.68-3.80 (4H, m), 3.48-3.67 (6H, m), 3.27-3.48 (4H, m), 2.90-3.04 (4H, m), 2.85 (3H, d, J=4.5 Hz), 2.19-2.39 (5H, m), 1.78 (1H, d, J=13.5 Hz), 1.69 (1H, d, J=13.5 Hz). Mass Spectrum (ESI) m/e=594.4 (M+1).

Provenance & Evidence