Sodium Carbonate → HCID 72544218, compound

HRID 73786Notes

Reaction equation

HRID 73786 reaction equation
[Cl:1][C:2]([F:27])([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:25])[C:12]2[CH:17]=[CH:16][C:15](F)=[C:14]([C:19]3[NH:23][N:22]=[CH:21][C:20]=3[F:24])[CH:13]=2)=[CH:6][CH:5]=1.[C:28]([O-:31])([O-])=O.[Na+].[Na+]>CS(C)=O.CCOC(C)=O>[Cl:1][C:2]([F:27])([F:26])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:25])[C:12]2[CH:17]=[CH:16][C:15]([N:10]3[CH2:7][CH2:6][C@@H:28]([OH:31])[CH2:11]3)=[C:14]([C:19]3[NH:23][N:22]=[CH:21][C:20]=3[F:24])[CH:13]=2)=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 10340Sodium CarbonateHCID 86702624N-(4-(chlorodifluoromethoxy)phenyl)-4-fluoro-3-(4-fluoro-1H-pyrazol-5-yl)benzamide

Product 1

HCID 72544218HCID 72544218, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-(4-(chlorodifluoromethoxy)phenyl)-4-fluoro-3-(4-fluoro-1H-pyrazol-5-yl)benzamide (Stage 24.1, 62 mg, 0.147 mmol), R-3-hydroxypyrrolidine (0.031 mL, 0.206 mmol) and TEA (0.062 mL, 0.442 mmol) in DMSO (0.5 mL) was stirred at 100° C. for 16 h. The RM was diluted with EtOAc (30 mL), treated with sat. aq. Na2CO3 (20 mL) and extracted with EtOAc. The combined extracts were washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by preparative HPLC (Condition 10). Fractions containing pure product were combined, treated with sat. aq. Na2CO3 and the MeCN was removed under reduced pressure. The aq. residue was extracted with DCM and the combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The residue was dissolved in DCM and treated with n-hexane to give the title product as a white solid. HPLC (Condition 5) tR=6.61 min, UPLC-MS (Condition 3) tR=1.01 min, m/z=467.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.69-1.95 (m, 2H) 2.79 (d, J=10.56 Hz, 1H) 3.06-3.20 (m, 2H) 3.22-3.35 (m, 1H) 4.13-4.30 (m, 1H) 4.79-4.96 (m, 1H) 6.75-6.92 (m, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.86 (m, J=9.38 Hz, 5H) 10.11 (s, 1H) 12.67-13.12 (m, 1H).

Workup

  1. extractionextracted with EtOAc
  2. washThe combined extracts were washed with water (20 mL) and brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. customthe solvent was evaporated off under reduced pressure
  5. customto give a crude product which
  6. customwas purified by preparative HPLC (Condition 10)
  7. additionFractions containing pure product
  8. additiontreated with sat. aq. Na2CO3
  9. customthe MeCN was removed under reduced pressure
  10. extractionThe aq. residue was extracted with DCM
  11. dry with materialthe combined extracts were dried over Na2SO4
  12. customthe solvent was evaporated off under reduced pressure
  13. dissolutionThe residue was dissolved in DCM
  14. additiontreated with n-hexane

Sources & evidence

ORD record
ord-50b779ce9d1a4eae9ab086e99fa7e46e
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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