Trifluoroacetic acid → HCID 89783465, compound

HRID 1055848Notes

Reaction equation

HRID 1055848 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[OH:10].Cl[C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([C:22]3[NH:30][C:29]4[CH2:28][CH2:27][NH:26][C:25](=[O:31])[C:24]=4[CH:23]=3)[CH:16]=[CH:17][CH:18]=2)[N:13]=1.C(O)(C(F)(F)F)=O>CN(C=O)C.CS(C)=O>[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[O:10][C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[C:15]([C:22]3[NH:30][C:29]4[CH2:28][CH2:27][NH:26][C:25](=[O:31])[C:24]=4[CH:23]=3)[CH:16]=[CH:17][CH:18]=2)[N:13]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 97072-FluorophenolHCID 24758Sodium hydrideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783465HCID 89783465, compoundYield 38.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To NaH (60 wt % in mineral oil; 0.071 g, 1.763 mmol) in 1 mL DMF was added 2-fluorophenol (0.163 ml, 1.763 mmol). After 10 min, a clear/colorless solution resulted. 2-(2-Chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 0.075 g, 0.252 mmol) was added and the reaction became dark red. The reaction was heated to 70° C. After 1 h, the temperature was increased to 90° C. After 4 h, the reaction was cooled to RT and stirred overnight. The reaction was then cooled to 0° C. and quenched with TFA (0.136 ml, 1.763 mmol), diluted with 1 mL DMSO, filtered, and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 15-100% ACN/H2O with 0.1% TFA); product-containing fractions were concentrated in vacuo then treated with saturated aq. NaHCO3 and DCM. The aq. layer was extracted 3×DCM and combined organics dried over Na2SO4, filtered, and concentrated in vacuo to give 2-(2-(2-fluorophenoxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.036 g, 0.096 mmol, 38% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.91 (1H, br. s), 8.52 (1H, d, J=8.8 Hz), 8.12 (1H, dd, J=7.6, 1.4 Hz), 7.74-7.89 (1H, m), 7.36-7.66 (6H, m), 6.85-6.99 (2H, m), 3.32-3.36 (2H, m), 2.43 (2H, t, J=6.9 Hz). m/z (ESI, +ve) 374.2 (M+H)+.

Workup

  1. customa clear/colorless solution resulted
  2. waitAfter 1 h
  3. temperaturethe temperature was increased to 90° C
  4. waitAfter 4 h
  5. temperaturethe reaction was cooled to RT
  6. temperatureThe reaction was then cooled to 0° C.
  7. filtrationfiltered
  8. custompurified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 15-100% ACN/H2O with 0.1% TFA)
  9. concentrationproduct-containing fractions were concentrated in vacuo
  10. additionthen treated with saturated aq. NaHCO3 and DCM
  11. extractionThe aq. layer was extracted 3×DCM
  12. dry with materialcombined organics dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b25ce641befa4f418a3a358176ec6114
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…