p-Toluenesulfonic acid → Talazoparib tosylate

Participants

Reaction Conditions

Reaction Steps

Variation 1: 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 (12.4 g) 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. The mixture was 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 (16.0 g, 89% yield). LC-MS (ESI) m/z: 381 (M+1)+. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 2.29 (s, 3H), 3.67 (s, 3H), 4.97-5.06 (m, 2H), 6.91-6.94 (dd, J1=2, J2=10.8 Hz, 1H), 7.06-7.19 (m, 5H), 7.19-7.51 (m, 4H), 7.74 (s, 1H), 7.87 (s, 1H), 10.32 (brs, 1H), 12.36 (s, 1H).

Provenance & Evidence