Phenol → HCID 89784005, compound

HRID 1055867Notes

Reaction equation

HRID 1055867 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[CH2:27][CH2:26][NH:25][C:24](=[O:30])[C:23]=4[CH:22]=3)[CH:15]=[CH:16][CH:17]=2)[N:12]=1>CN(C=O)C>[O:9]([C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[C:14]([C:21]3[NH:29][C:28]4[CH2:27][CH2:26][NH:25][C:24](=[O:30])[C:23]=4[CH:22]=3)[CH:15]=[CH:16][CH:17]=2)[N:12]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89784005HCID 89784005, compoundYield 80.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To NaH (60 wt % in mineral oil; 0.047 g, 1.176 mmol) in 1 mL DMF was added phenol (0.111 g, 1.176 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, 0.050 g, 0.168 mmol) was added and the reaction became dark red. After 30 min at RT, the reaction was heated to 70° C. The reaction was judged complete after 5 h at 70° C., and was cooled to RT and quenched with saturated aq. NH4Cl and EtOAc. The organic layer was sequentially washed with water, and saturated aq. NaCl, then dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography using 0-50%-90/10 DCM/MeOH in DCM. The product-containing fractions were concentrated to afford 2-(2-phenoxyquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.048 g, 0.135 mmol, 80% yield) as a light-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 11.04 (1H, br. s), 8.49 (1H, d, J=8.8 Hz), 8.12 (1H, dd, J=7.6, 1.6 Hz), 7.74-7.87 (1H, m), 7.56-7.66 (2H, m), 7.33-7.52 (5H, m), 6.84-7.01 (2H, m), 3.31-3.38 (2H, m), 2.39 (2H, t, J=6.9 Hz). m/z (ESI, +ve) 356.0 (M+H)+.

Workup

  1. customa clear/colorless solution resulted
  2. waitAfter 30 min at RT
  3. waitThe reaction was judged complete after 5 h at 70° C.
  4. temperaturewas cooled to RT
  5. customquenched with saturated aq. NH4Cl and EtOAc
  6. washThe organic layer was sequentially washed with water, and saturated aq. NaCl
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. additionThe material was treated with DCM
  11. custompurified by silica gel chromatography
  12. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-ce87d9354bc34641ab07ed20ebb306f3
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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