p-Toluenesulfonic acid → Talazoparib tosylate

Participants

Reaction Conditions

Reaction Steps

Variation 2: To a solution of (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (0.24 kg) in THF (40 vols) was slowly added a solution of TsOH (1.05 equiv.) in THF (5 vols) at 50° C.˜54° C. The mixture was stirred for additional 30 minutes at this temperature. The mixture was then concentrated down to 3˜5 vols by distillation at 30° C.-40° C. under reduced pressure (vacuum:—0.07 MPa˜—0.08 MPa). Further removal of THF solvent was achieved by adding acetone (20 vols) and then distilling down to 3˜5 vols under reduced pressure, which was repeated three times. After removal of THF solvent and distilling, the mixture was re-slurried with 12 vols of acetone for 14˜15 hours at 50° C.˜54° C. The mixture was then cooled down to 5° C. and filtered under nitrogen protection. The solid was dried at 60° C. for 17 hours. It gave the title compound as a white crystal solid (0.31 kg, 91.7% yield, 99.65% purity).

Provenance & Evidence