Potassium Carbonate → HCID 10391639, compound

Participants

Reaction Conditions

Reaction Steps

4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(piperidin-4-yl)methoxy]quinazoline (Example 3, 104 mg, 0.25 mmol) was dissolved in DMA (5 ml). Potassium carbonate (138 mg, 1.00 mmol) and 1-bromo-2-methoxyethane (24 μl, 0.25 mmol) were added. The mixture was stirred at 60° C. for 4 hours. Further potassium carbonate (138 mg, 1.00 mmol) and 1-bromo-2-methoxyethane (24 μl, 0.25 mmol) were added; heating was continued at 60° C. for a further 4 hours. The solvent was evaporated and the residue was partitioned between DCM (20 ml) and water (20 ml). The aqueous layer was extracted with DCM (2×10 ml) and the extractions combined with the DCM layer. The combined DCM fractions were filtered through a silicone-treated filter paper and evaporated. The residue was purified by chromatography, eluting with 0 to 2.5% (7:1 MeOH/concentrated aqueous NH4OH) in DCM. The appropriate fractions were combined and evaporated, and the crude product (40 mg) re-dissolved in 1:1 methanol/DCM (5 ml). Ethereal HCl (1M, 0.5 ml) was added, and the mixture evaporated. Crystallisation from iso-propanol/diethyl ether gave the title product as a hydrochloride salt, a yellow solid (28 mg, 20%); 1H NMR (hydrochloride salt): 1.60-1.75 (m, 2H), 2.00-2.05 (m, 2H), 2.16 (m, 1H), 2.95-3.10 (m, 2H), 3.22 (t, 2H), 3.29 (s, 3H), 3.50-3.57 (m, 2H), 3.70 (t, 2H), 3.99 (s, 3H), 4.12 (d, 2H), 7.34 (dd, 1H), 7.39 (s, 1H), 7.51 (dd, 1H), 7.61 (dd, 1H), 8.46 (s, 1H), 8.78 (s, 1H), 10.08 (br. s, 1H); Mass Spectrum: 475.5, 477

Provenance & Evidence