Hydrochloric Acid → 2-[6-(4-Methylpiperazin-1-yl)-pyrimidin-4-yl]-4-pyridin-3-yl-1,2-dihydro-3H-pyrazol-3-one dihydrochloride

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Reaction Steps

146 mg (663 μmol) of the compound from Example 3A, 115 mg (552 μmol) of the compound from Example 6A and 13 mg (55 μmol) of camphor-10-sulfonic acid are dissolved in 5 ml of anhydrous ethanol, and the mixture is heated under reflux overnight. After cooling, the mixture is concentrated and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid). The resulting mixture of target product and intermediate is dissolved in 5 ml of anhydrous ethanol, 109 mg (607 μmol) of a 30% strength methanolic sodium methoxide solution are added and the mixture is stirred at RT for 1 h. The mixture is then neutralized with 1 M hydrochloric acid and concentrated, and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid). The mixture of target product and intermediate obtained this time is again dissolved in 5 ml of anhydrous ethanol, 99 mg (552 μmol) of a 30% strength methanolic sodium methoxide solution are added and the mixture is stirred at RT for 2 h. The mixture is then again neutralized with 1 M hydrochloric acid and concentrated, and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% conc. hydrochloric acid). This gives 9 mg (4% of theory) of the title compound.

Provenance & Evidence