Sodium hydride → 5-isopropyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide

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Reaction Steps

To a solution of 250 mg of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide (Example 13) in 15 ml of THF was added 48 mg of NaH. The mixture was stirred for 2 h at room temperature before 120 mg of 4,6-dimethoxy-2-methylsulfonylpyrimidine was added. Stirring was continued for 16 h at reflux. Eventually, the solvent was evaporated and the remaining residue was partitioned between 50 ml of 10% aqueous citric acid and 50 ml of ethyl acetate. The organic layer was separated and the aqueous layer was extracted two more times with 50 ml of ethyl acetate. The combined organic layers were washed with water and brine, dried over MgSO4 and evaporated. The crude product was purified by chromatography on prep. tlc-plates coated with silica gel with ethyl acetate:methanol: sat. aqueous ammonia 8:2:1 to give 71 mg of 5-isopropyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide as a beige foam. LC-MS: tR=5.50 min, [M+1]+=623.29, [M−1]+=621.40.

Provenance & Evidence