Hydrochloric Acid → 4-benzyl-3-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one

HRID 1878737Notes

Reaction equation

HRID 1878737 reaction equation
[CH2:1]([C:8]1[CH:13]=[CH:12][N:11]=[C:10](F)[C:9]=1[CH2:15][CH2:16][O:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=2)[N:21]=[CH:20][CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C1C[O:34]CC1>>[CH2:1]([C:8]1[CH:13]=[CH:12][NH:11][C:10](=[O:34])[C:9]=1[CH2:15][CH2:16][O:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:28][CH3:29])=[CH:25][CH:26]=2)[N:21]=[CH:20][CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 688105894-(2-(4-Benzyl-2-fluoropyridin-3-yl)ethoxy)-7-methoxyquinoline

Product 1

HCID 598430694-benzyl-3-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one

Conditions

Temperature
70 °C

Procedure

An NMR tube was charged with 4-(2-(4-benzyl-2-fluoropyridin-3-yl)ethoxy)-7-methoxyquinoline (0.0061 g, 0.016 mmol), 0.5 mL THF and 0.2 mL 35% HCl. The tube was heated to 70° C. for 40 h, and cooled. The solvent was removed under a stream of nitrogen, and the residue was diluted to 0.6 mL with MeOH, and treated with Si-carbonate (0.022 g, 0.016 mmol). The solution was filtered and concentrated in vacuo. A sample was scouted for prep purification using a 2.1×50 mm Xterra MS C18 column with a 3.5 μm particle size (PN 186000400); A=11 mM NH4HCO3 in water, pH adjusted to 8.5 with concentrated NH4OH; B=Acetonitrile; gradient: initial@1 mL/min, 10% B; 0→5 min@1 mL/min, linear gradient to 100% B; 5→6.9 min@1 mL/min, isocratic at 100% B; 6.9→6.95 min@1 mL/min, linear gradient to 110% B, 8 min end. A major peak was observed at 3.07. The sample was purified using a 19×150 mm Waters Xterra Prep C18 OBD column (100 Å pore diameter, 5 μm particle size, spherical shape, PN 186002381; Gradient: 0→5 min@20 mL/min, 25% B; 5.0→35 min@20 mL/min, linear gradient to 55% B; 35→45@20 mL/min, isocratic at 55% B, 45→55 min@20 mL/min, step to 100% B; 55→60 min@20 mL/min, step to 25% B; 60 min end). A=11 mM NH4HCO3 in water, pH adjusted to 8.5 with concentrated NH4OH; B=Acetonitrile. A band that eluted from 20.9-21.9 minutes was isolated. The solvent was removed in vacuo to afford 4-benzyl-3-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1 H)-one. 1H NMR (400 MHz, CDCl3) δ ppm 3.28 (t, J=6.75 Hz, 2 H) 3.93 (s, 3 H) 4.07 (s, 2 H) 4.36 (t, J=6.65 Hz, 2 H) 6.09 (d, J=6.75 Hz, 1 H) 6.66 (d, J=5.38 Hz, 1 H) 7.08 (dd, J=9.15, 2.49 Hz, 1 H) 7.13-7.17 (m, 2 H) 7.19-7.25 (m, 2 H) 7.26-7.32 (m, 2 H) 7.34 (d, J=2.54 Hz, 1 H) 8.03 (d, J=9.19 Hz, 1 H) 8.62 (d, J=5.18 Hz, 1 H) 11.96 (br. s., 1H). 13C NMR (101 MHz, CDCl3) δ ppm 26.72 (s, 1 C) 38.97 (s, 1 C) 55.43 (s, 1 C) 66.50 (s, 1 C) 99.65 (s, 1 C) 107.20 (s, 1 C) 109.62 (s, 1 C) 116.02 (s, 1 C) 118.12 (s, 1 C) 123.11 (s, 1 C) 126.28 (s, 1 C) 126.79 (s, 1 C) 128.73 (s, 2 C) 128.81 (s, 2 C) 131.53 (s, 1 C) 138.24 (s, 1 C) 151.17 (s, 1 C) 151.82 (s, 1 C) 152.21 (s, 1 C) 160.85 (s, 1 C) 161.60 (s, 1 C) 164.55 (s, 1 C). MS (ESI pos. ion) m/z (MH+): 387.2, calcd for C24H22N2O3+H+=387.2.

Workup

  1. temperaturecooled
  2. customThe solvent was removed under a stream of nitrogen
  3. additionthe residue was diluted to 0.6 mL with MeOH
  4. filtrationThe solution was filtered
  5. concentrationconcentrated in vacuo
  6. customA sample was scouted for prep purification
  7. custom0→5 min@1 mL/min, linear gradient
  8. custom5→6.9 min@1 mL/min
  9. custom6.9→6.95 min@1 mL/min, linear gradient
  10. customto 110% B, 8 min end
  11. customThe sample was purified
  12. customC18 OBD column (100 Å pore diameter, 5 μm particle size, spherical shape, PN 186002381; Gradient: 0→5 min@20 mL/min, 25% B; 5.0→35 min@20 mL/min, linear gradient to 55% B; 35→45@20 mL/min, isocratic at 55% B, 45→55 min@20 mL/min, step to 100% B; 55→60 min@20 mL/min, step to 25% B; 60 min end)
  13. washA band that eluted from 20.9-21.9 minutes
  14. customwas isolated
  15. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-fb9c088f770f4c53a4bc84505397c028
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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