2-Fluoroaniline → 2-(2-((2-fluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1055843Notes

Reaction equation

HRID 1055843 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH2:6].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>CN(C=O)C>[F:3][C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH:6][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

5

Reactant 3

HCID 95842-FluoroanilineHCID 24758Sodium hydrideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 897836842-(2-((2-fluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneYield 22.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To NaH (60 wt % in mineral oil; 0.071 g, 1.763 mmol) in 1 mL DMF was added 2-fluoroaniline (0.196 g, 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 as a solid and the reaction became dark red. After 30 min, the reaction was heated at 70° for 2 h. The reaction mixture was then cooled to RT and partitioned between saturated aq. NH4Cl and EtOAc. The organic layer was washed with saturated aq. NaHCO3 (1×), water (1×), saturated aq. NaCl (1×), and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was suspended in DCM and filtered, rinsing 2×DCM, dried in vacuo to give 2-(2-((2-fluorophenyl)amino)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (0.021 g, 0.056 mmol, 22% yield) as a dull-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.04 (1H, br. s.), 9.32 (1H, s), 8.14 (1H, s), 7.97 (1H, dd, J=7.5, 1.5 Hz), 7.84-7.93 (1H, m), 7.56-7.62 (1H, m), 7.34-7.44 (1H, m), 7.22-7.33 (3H, m), 7.15-7.21 (1H, m), 6.86-6.95 (2H, m), 3.32-3.41 (2H, m), 2.51-2.57 (2H, m). m/z (ESI, +ve) 373.0 (M+H)+.

Workup

  1. customa clear/colorless solution resulted
  2. waitAfter 30 min
  3. temperaturethe reaction was heated at 70° for 2 h
  4. custompartitioned between saturated aq. NH4Cl and EtOAc
  5. washThe organic layer was washed with saturated aq. NaHCO3 (1×), water (1×), saturated aq. NaCl (1×)
  6. dry with materialthe organics were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. filtrationfiltered
  10. washrinsing 2×DCM
  11. customdried in vacuo

Sources & evidence

ORD record
ord-d431c4db75d740aaa2778799a839bfc8
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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