Tetrahydrofuran → 2-[6-(3-Hydroxyazetidin-1-yl)pyrimidin-4-yl]-4-(1H-1,2,3-triazol-1-yl)-1,2-dihydro-3H-pyrazol-3-one

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Reaction Steps

348 mg (1.7 mmol) of the compound from Example 3A and 300 mg (1.7 mmol) of the compound from Example 11A are initially introduced into a mixture of 6 ml THF and 6 ml ethanol. 63 mg (0.3 mmol) p-toluenesulfonic acid monohydrate are added and the mixture is reacted in a single mode microwave (CEM Explorer) at 130° C. for 1.5 h. The mixture is allowed to cool to RT, a further 50 mg of the compound from Example 3A and a spatula-tip of p-toluenesulfonic acid monohydrate are added and the mixture is heated at 150° C. for 1 h. It is allowed to cool to room temperature and is decanted off from the solid and the solid is washed several times with THF (solid batch 1). The supernatant decanted off and the wash solution are combined, the mixture is concentrated and 5 ml ethanol and 5 ml THF and a spatula-tip of p-toluenesulfonic acid monohydrate are added to the residue obtained. The mixture is reacted again in a single mode microwave (CEM Explorer) at 150° C. for 2 h. It is allowed to cool to RT and the solid formed is filtered off (solid batch 2). The filtrate is concentrated, 3 ml DMSO are added to the residue and purification is carried out by means of preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). The product-containing fractions are combined and concentrated. The residue is dissolved in ethanol, a little THF is added and the mixture is concentrated, with formation of a precipitate. The solid is filtered off and washed with THF (solid batch 3). The three solid batches obtained are combined and the mixture is dried under a high vacuum.

Provenance & Evidence