4-Methoxybenzylamine → 1'-(7-Fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6'-(4-morpholinyl)-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridin]-5'-amine

Participants

Reaction Steps

To a stirred solution of 5′-bromo-1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (60 mg, 0.102 mmol) in 1,4-dioxane (1.5 mL) was added 4-methoxybenzylamine (19.78 μL, 0.152 mmol) and sodium tert-butoxide (19.53 mg, 0.203 mmol). The reaction was heated at reflux for 2 h. After this time the reaction was partitioned between EtOAc (50 mL) and water (15 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. The crude mixture was then dissolved in DCM (3 mL) and treated with TFA (0.5 mL) and stirred at rt for 2 h. At this time the reaction was evaporated in vacuo and partitioned between DCM (30 mL) and NaHCO3 (10 mL, sat. aqueous solution). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. The resulting crude product was purified by reverse phase HPLC (10 to 60% acetonitrile water) to give 1′-(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-6′-(4-morpholinyl)-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridin]-5′-amine. 1H NMR (400 MHz, chloroform-d) δ ppm 8.71-8.78 (1H, m), 7.77-7.94 (4H, m), 7.40 (1H, ddd, J=7.2, 4.9, 1.6 Hz), 7.18-7.26 (1H, m), 6.10-6.15 (1H, m), 4.13 (2H, q, J=7.2 Hz), 3.92-4.02 (2H, m), 3.68-3.86 (4H, m), 3.51-3.60 (2H, m), 2.67-2.82 (4H, m), 2.24-2.41 (5H, m), 1.67-1.84 (2H, m). Mass Spectrum (ESI) m/e=527.2 (M+1).

Provenance & Evidence