Phenol → HCID 89783487, compound

HRID 1055860Notes

Reaction equation

HRID 1055860 reaction equation
[H-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[C:14]([C:21]3[NH:29][C:28]4[CH:27]([CH3:30])[CH2:26][NH:25][C:24](=[O:31])[C:23]=4[CH:22]=3)[CH:15]=[CH:16][CH:17]=2)[N:12]=1.C(O)(C(F)(F)F)=O>CN(C=O)C.CS(C)=O>[CH3:30][CH:27]1[CH2:26][NH:25][C:24](=[O:31])[C:23]2[CH:22]=[C:21]([C:14]3[CH:15]=[CH:16][CH:17]=[C:18]4[C:13]=3[N:12]=[C:11]([O:9][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH:20]=[CH:19]4)[NH:29][C:28]1=2

Participants

7

Reactant 4

HCID 996PhenolHCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 89783271HCID 89783271, compound

Product 1

HCID 89783487HCID 89783487, compoundYield 63.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a slurry of NaH (60% in mineral oil; 0.036 g, 0.898 mmol) in 0.5 mL DMF was added phenol (0.085 g, 0.898 mmol). After 10 min, 2-(2-chloroquinolin-8-yl)-7-methyl-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 27; 0.040 g, 0.128 mmol) was added and the reaction was heated to 80° C. for 2 h. The reaction was cooled, treated with DMSO and TFA (0.069 ml, 0.898 mmol), filtered, and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 15-100% ACN/H2O with 0.1% TFA); product-containing fraction was treated with saturated aq. NaHCO3 and DCM. The organic layer was separated, and the aq. layer was extracted 3×DCM. The combined organic layers were then dried over Na2SO4, filtered, and concentrated in vacuo to give rac-7-methyl-2-(2-phenoxyquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.030 g, 0.081 mmol, 63% yield) as an off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.10 (1H, br. s), 8.50 (1H, d, J=9.0 Hz), 8.13 (1H, dt, J=7.5, 0.7 Hz), 7.80 (1H, dt, J=7.9, 0.7 Hz), 7.55-7.65 (2H, m), 7.49 (1H, t, J=7.7 Hz), 7.33-7.45 (4H, m), 6.83-6.99 (2H, m), 3.44 (1H, ddt, J=12.3, 5.6, 0.6, 0.6 Hz), 2.92-3.06 (1H, m), 2.55-2.60 (1H, m), 0.90 (3H, d, J=6.8 Hz). m/z (ESI, +ve) 370.1 (M+H)+.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationfiltered
  3. custompurified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 15-100% ACN/H2O with 0.1% TFA)
  4. additionproduct-containing fraction
  5. additionwas treated with saturated aq. NaHCO3 and DCM
  6. customThe organic layer was separated
  7. extractionthe aq. layer was extracted 3×DCM
  8. dry with materialThe combined organic layers were then dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dc7f5220878c46d592bae4040a6c3ce8
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…