Thionyl Chloride → 2-Chloro-4-(chloromethyl)pyridine--hydrogen chloride (1/1)

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Reaction Steps

A mixture of 2-chloro-4-hydroxymethylpyridine (180 mg, 1.25 mmol), thionyl chloride (Q02 ml) in toluene (10 ml) was stirred at ambient temperature for 1 hour. The volatiles were removed by evaporation to give 2-chloro-4-chloromethylpyridine hydrochloride (180 mg, 0.9 mmol). A mixture of 7-hydroxy-6-methoxy-4-phenoxyquinazoline (268 mg, 1 mmol), (prepared as described for the starting material in Example 13), potassium carbonate (680 mg, 5 mmol) and DMF (10 ml) was added to this crude product and the mixture was heated at 90° C. for 1 hour. The mixture was allowed to cool, diluted with water and extracted with ethyl acetate (3×70 ml). The extracts were combined, washed with water (×3) and brine, dried (MgSO4) and the solvent removed by evaporation to give 7-((2-chloro-4-pyridyl)methoxy)-6-methoxy-4-phenoxyquinazoline (260 mg, 66%) as a solid. 1H NMR Spectrum: (DMSOd6) 4.00(s, 3H); 5.45(s, 2H); 7.30(m, 3H); 7.42(s, 1H); 7.4-7.5(m, 3H); 7.60(s, 1H); 7.62(s, 1H); 8.44(d, 1H); 8.52(s, 1H) MS-ESI: 394 [MH]+

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