Dimethyl Sulfate → 5-isopropyl-N-[6-(4-methoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-2-pyridine sulfonamide

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Reaction Steps

To a solution of 300 mg of 5-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-2-(4-pyridyl)4-pyrimidinyl]-2-pyridine sulfonamide (Example 1f) and 1.47 g of 4-methoxy-2-butynol (prepared starting from 2-butyn-1,4-diol and dimethylsulfate following the procedure given in Bull. Chem. Soc. Japan 28 (1955), 80-83) in 15 ml of DMF was carefully added 234 mg of 55% NaH in mineral oil. The brown solution stirred for 24 h at room temperature before further 120 mg of 55% NaH in mineral oil was added. Stirring was continued for 24 h. The mixture was diluted with 100 ml of 10% aqueous citric acid and extracted four times with 50 ml of ethyl acetate. The combined organic phases were washed twice with 50 ml of water, dried over MgSO4 and evaporated. The crude product was purified by column chromatography on silica gel eluting with ethyl acetate to give 154 mg of 5-isopropyl-N-[6-(4-methoxy-but-2-ynyloxy)-5-(2-methoxy-phenoxy)-2-pyridin-4-yl-pyrimidin-4-yl]-2-pyridine sulfonamide as a yellow solid. LC-MS: tR=4.84 min, [M+1]+=576.42, [M−1]−=574.37.

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