2-Butyne-1,4-diol → 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide

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Reaction Conditions

Reaction Steps

To a solution of 11.02 g of 2-butyne-1,4-diol in 100 ml of DMF and 30 ml of DMPU was added 2.8 g sodium hydride in portions. After completion of the addition stirring was continued for 1.5 h followed by the addition of 2.78 g of 5-isopropyl-N-[6-chloro-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide. The mixture was heated to 90° C. and stirred for 65 h. The solvent was removed in vacuo, the residue was taken up in 250 ml of 10% aqueous citric acid and extracted twice with 250 ml of ethyl acetate. The organic phase was washed with water and brine, dried over MgSO4 and evaporated. Column chromatography of the crude product on silica gel eluting with hexane:ethyl acetate 1:1 to 1:4 furnished 1.27 g of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)4-pyrimidinyl]-2-pyridine sulfonamide as a brown solid. Beige crystals were obtained for analytical purposes after crystallisation of a part of the isolated product from 2-propanol. LC-MS: tR=4.50 min, [M+1]+=485.27, [M−1]−=483.41.

Provenance & Evidence