Trifluoroacetic acid → HCID 45137393, compound

HRID 559639Notes

Reaction equation

HRID 559639 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH:14]([NH:17][C:18]([C:20]2[C:21]3[CH:28]=[N:27][N:26]([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[C:22]=3[CH:23]=[N:24][CH:25]=2)=[O:19])[CH2:15][CH3:16])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH:14]([NH:17][C:18]([C:20]2[C:21]3[CH:28]=[N:27][N:26]([C:29]4[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=4)[C:22]=3[CH:23]=[N:24][CH:25]=2)=[O:19])[CH2:15][CH3:16])[CH2:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 59278352HCID 59278352, compound

Product 1

HCID 45137393HCID 45137393, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 3-(1-{[1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]-amino}-propyl)-piperidine-1-carboxylic acid tert-butyl ester (1.1 g, 2.3 mmol) was added a 10% solution of trifluoroacetic acid in dichloromethane (10 mL). The mixture was stirred at room temperature overnight and the reaction was monitored by HPLC-MS indicating incomplete conversion. Additional trifluoroacetic acid (1 mL) was added. The mixture stirred until HPLC-MS indicated starting material was consumed. The mixture was concentrated in vacuo and the residue was diluted with EtOAc (100 mL), made basic with saturated aqueous sodium bicarbonate (pH=10), washed with brine, and dried over sodium sulfate, filtered and concentrated. A portion of the crude material was purified by reversed-phase HPLC (Sunfire PrepC18 OBD 5 mM 30×150 mm column) eluting with a gradient of 15-85% acetonitrile in water (0.1% TFA). The fractions from the column were concentrated to remove acetonitrile made basic with saturated aqueous sodium bicarbonate and extracted with EtOAc. The organic layers were dried and concentrated to afford the title compound as a white foam.

Workup

  1. stirringThe mixture stirred until HPLC-MS
  2. customwas consumed
  3. concentrationThe mixture was concentrated in vacuo
  4. additionthe residue was diluted with EtOAc (100 mL)
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customA portion of the crude material was purified by reversed-phase HPLC (Sunfire PrepC18 OBD 5 mM 30×150 mm column)
  10. washeluting with a gradient of 15-85% acetonitrile in water (0.1% TFA)
  11. concentrationThe fractions from the column were concentrated
  12. customto remove acetonitrile
  13. extractionextracted with EtOAc
  14. customThe organic layers were dried
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-98299b7ad6a5443987599bf284e5bb16
Source dataset
uspto-grants-2011_11
Patent number
US08063065B2

Reaction notes

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