2-Hydroxy-succinic acid (231 mg, 1.72 mmol) was dissolved in 100 mL of methanol under stirring at room temperature, and (R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one 1 (560 mg, 1.233 mmol), 200 mL of methanol and 100 mL of water was then added to the solution in batch. Upon completion of the addition, the reaction system was heated at 50° C. in an oil bath in dark until a clear solution was obtained. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to remove the solvent to give a yellow solid. The resulting solid was dissolved in 100 mL of acetonitrile, and the mixture was heated to reflux in dark for 1.5 hours. The oil bath was removed. The reaction system was naturally cooled down to room temperature and filtered to give the title compound (R,Z)-2-(5-fluoro-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-5-(2-hydroxy-3-morpholin-4-yl-propyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one malate 24 (718 mg, yield 99%) as a yellow solid.
