p-Toluenesulfonic acid → Talazoparib tosylate

HRID 1027507Notes

Reaction equation

HRID 1027507 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[NH:15][C@H:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C@@H:13]([C:23]3[N:27]([CH3:28])[N:26]=[CH:25][N:24]=3)[C:6]3=[N:7][NH:8][C:9](=[O:12])[C:10]([CH:11]=1)=[C:5]23.[CH3:29][C:30]1[CH:31]=[CH:32][C:33]([S:36]([OH:39])(=[O:38])=[O:37])=[CH:34][CH:35]=1>C1COCC1>[S:36]([C:33]1[CH:34]=[CH:35][C:30]([CH3:29])=[CH:31][CH:32]=1)([OH:39])(=[O:38])=[O:37].[F:1][C:2]1[CH:3]=[C:4]2[NH:15][C@H:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C@@H:13]([C:23]3[N:27]([CH3:28])[N:26]=[CH:25][N:24]=3)[C:6]3=[N:7][NH:8][C:9](=[O:12])[C:10]([CH:11]=1)=[C:5]23

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 135565082Talazoparib

Product 1

HCID 135565654Talazoparib tosylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

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).

Workup

  1. concentrationThe 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)
  2. customFurther removal of THF solvent
  3. additionby adding acetone (20 vols)
  4. distillationdistilling down to 3˜5 vols under reduced pressure, which
  5. filtrationfiltered under nitrogen protection
  6. customThe solid was dried at 60° C. for 17 hours

Sources & evidence

ORD record
ord-d95ebed712e04de0989bc592c7fa78b1
Source dataset
uspto-grants-2014_05
Patent number
US08735392B2

Reaction notes

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