LY2955303

1433497-65-4

1433497-19-8

1. THF (1790 L) was added to the reactor followed by methyl 4-[5-(3,5-di-tert-butylphenyl)-1-[4-(4-methylpiperazine-1-carbonyl)phenyl]pyrazol-3-yl]benzoate (358 g, 0.605 mol) and water (1140 mL), keeping the temperature at 8-12 °C. 2. lithium hydroxide monohydrate (38 g, 0.905 mol) was added one time and the reaction mixture was stirred at 8-12 °C for 16 hours. 3. After completion of the reaction, EtOAc (30 L) was added and the pH of the mixture was adjusted to 5 with 1N HCl. 4. The two phases were separated and the aqueous layer was extracted with EtOAc (2 x 10 L). The organic layers were combined, dried with sodium sulfate, filtered and the solvent was removed under reduced pressure to give a solid product. 5. The crude product was purified by column chromatography using DCM/MeOH (20/1) as eluent to give a light yellow solid. 6. The solid was ground in a solvent mixture of acetonitrile/MTBE (1/3, 4 L) for 1 h. The solid was collected by filtration. 7. The solid was dried under vacuum at 50 °C for 72 h to give 4-(5-(3,5-di-tert-butylphenyl)-1-(4-(4-methylpiperazine-1-carbonyl)phenyl)-1H-pyrazol-3-yl)benzoic acid (264.2 g, 75% yield) as a white solid. lc-es/ms m/z 579 [M + H]+.