Chloroacetonitrile → HCID 9980764, compound

Participants

Reaction Conditions

Reaction Steps

4-(3-Chloro-2-fluoroanilino)-7-methoxy-6-[(piperidin-4-yl)oxy]quinazoline (Example 2, 70 mg, 0.17 mmol) was dissolved in DMA (5 ml). Potassium carbonate (96 mg, 0.70 mmol) and chloroacetonitrile (17 μl, 0.25 mmol) were added. The mixture was stirred at 60° C. for 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% (7:1 MeOH/concentrated aqueous NH4OH) in DCM. The appropriate fractions were combined and evaporated, and the residue triturated with diethyl ether, giving the product as a white solid (28 mg, 36%); 1H NMR: 1.67-1.80 (m, 2H), 2.03-2.13 (m, 2H), 2.46 (m, 2H), 2.77-2.85 (m, 2H), 3.76 (s, 2H), 3.92 (s, 3H), 4.55 (m, 1H), 7.20 (s, 1H), 7.27 (dd, 1H), 7.47 (dd, 1H), 7.52 (dd, 1H), 7.80 (s, 1H), 8.35 (s, 1H), 9.54 (s, 1H); Mass Spectrum: 412.4, 444.4.

Provenance & Evidence