Hydrochloric Acid → HCID 90417505, compound

HRID 633534Notes

Reaction equation

HRID 633534 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[C:12]1[C:20]2[C:15](=[C:16]([O:21]C)[N:17]=[CH:18][CH:19]=2)[N:14]([CH3:23])[CH:13]=1.[F:24][C:25]1[CH:26]=[C:27]([OH:32])[CH:28]=[CH:29][C:30]=1[F:31].C([O-])([O-])=O.[Cs+].[Cs+].Cl>CS(C)=O.O1CCOCC1>[F:24][C:25]1[CH:26]=[C:27]([CH:28]=[CH:29][C:30]=1[F:31])[O:32][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH3:11])(=[O:9])=[O:10])=[CH:4][C:3]=1[C:12]1[C:20]2[CH:19]=[CH:18][NH:17][C:16](=[O:21])[C:15]=2[N:14]([CH3:23])[CH:13]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 759273,4-DifluorophenolHCID 90416744HCID 90416744, compound

Product 1

HCID 90417505HCID 90417505, compoundYield 38.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of Example 17C (0.1 g, 0.299 mmol), 3,4-difluorophenol (0.058 g, 0.449 mmol) and Cs2CO3 (0.146 g, 0.449 mmol) in DMSO (5 mL) was stirred at 110° C. for 12 hours, cooled and partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous Na2SO4), filtered, and concentrated. The resulting residue (0.13 g, 0.405 mmol) and 4M HCl in dioxane (4 M, 13 mL) was heated at 70° C. for 12 hours, cooled and concentrated. The residue was purified by reverse phase HPLC (C18, CH3CN/water (0.1% TFA), 10-100%) to afford the title compound (0.05 g, 0.116 mmol, 38.7%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.00 (d, J=5.3 Hz, 1H), 8.01 (d, J=2.4 Hz, 1H), 7.80 (dd, J=8.7, 2.4 Hz, 1H), 7.68 (s, 1H), 7.50 (dd, J=19.6, 9.2 Hz, 1H), 7.40 (ddd, J=11.5, 6.8, 2.9 Hz, 1H), 7.11 (d, J=8.6 Hz, 1H), 7.00 (d, J=7.7 Hz, 1H), 6.95-6.88 (m, 1H), 6.54 (d, J=6.3 Hz, 1H), 4.11 (s, 3H), 3.26 (s, 3H). MS (ESI+) m/z 431.0 (M+H)+.

Workup

  1. temperaturecooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried (anhydrous Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. temperaturecooled
  8. concentrationconcentrated
  9. customThe residue was purified by reverse phase HPLC (C18, CH3CN/water (0.1% TFA), 10-100%)

Sources & evidence

ORD record
ord-090056b8d1544a0d8e62f418b633039e
Source dataset
uspto-grants-2016_04
Patent number
US09321764B2

Reaction notes

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