Hydrochloric Acid → HCID 21083985, compound

HRID 347929Notes

Reaction equation

HRID 347929 reaction equation
Cl.[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[C:10]1[C:18]2[CH:17]=[CH:16][C:15](=[O:19])[N:14]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)=[CH:22][CH:21]=3)[C:13]=2[S:12][C:11]=1C(OCC)=O.Cl>O1CCOCC1>[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[C:10]1[C:18]2[CH:17]=[CH:16][C:15](=[O:19])[N:14]([C:20]3[CH:21]=[CH:22][C:23]([N:26]4[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]4)=[CH:24][CH:25]=3)[C:13]=2[S:12][CH:11]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 21084011HCID 21084011, compound

Product 1

HCID 21083985HCID 21083985, compoundYield 104.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of the compound of Example 112 (310 mg, 0.61 mmol) in dioxane (35 mL) was added 4M HCl(aq) (20 mL) and the mixture heated at reflux for 18 h. Reaction had not reached completion and so a few drops of concentratedHCI were added and reflux continued for 5 h. The reaction was quenched with saturated Na2CO3(aq) and extracted with DCM (×3). The combined DCM extracts were dried (Na2SO4), filtered and concentrated in vacuo. The crude product contained a small amount of residual ester starting material. The product was therefore dissolved in EtOH (15 mL) and heated at reflux with NaOH (50 mg) for 16 h. Solvent was removed in vacuo and the residue partitioned between DCM and saturated Na2CO3(aq). The DCM layer was washed with Na2CO3(aq) (×3), dried (Na2SO4) and concentrated in vacuo to give the pure title compound as an off-white solid (280 mg). δH (DMSO-d6) 8.10–7.95 (2H, m), 7.86 (1H, dt, J 9.5, 2.6 Hz), 7.74–7.63 (4H, m), 7.55–7.52 (2H, m), 6.92 (1H, d, J 9.5 Hz), 3.72–3.67 (8H, m), 2.67 (3H,s). LCMS (ES+) RT 2.47 minutes, 438 (M+H)+.

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 18 h
  3. customReaction
  4. additionso a few drops of concentratedHCI were added
  5. temperaturereflux
  6. customThe reaction was quenched with saturated Na2CO3(aq)
  7. extractionextracted with DCM (×3)
  8. dry with materialThe combined DCM extracts were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe product was therefore dissolved in EtOH (15 mL)
  12. temperatureheated
  13. temperatureat reflux with NaOH (50 mg) for 16 h
  14. customSolvent was removed in vacuo
  15. customthe residue partitioned between DCM and saturated Na2CO3(aq)
  16. washThe DCM layer was washed with Na2CO3(aq) (×3)
  17. dry with materialdried (Na2SO4)
  18. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f4d2db2b15bb4bed94878d1cd65e18e0
Source dataset
uspto-grants-2007_02
Patent number
US07176215B2

Reaction notes

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