Sodium hydride → HCID 69675865, compound

HRID 1616068Notes

Reaction equation

HRID 1616068 reaction equation
[OH:1][N:2]=[C:3]([NH2:5])[CH3:4].[H-].[Na+].[C:8]([O:12][C:13]([NH:15][CH:16]([C:18]1[C:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[C:26]([C:34](OC)=O)[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:38])[CH:24]=2)[N:19]=1)[CH3:17])=[O:14])([CH3:11])([CH3:10])[CH3:9]>C1COCC1>[F:38][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][CH:22]=1)[N:19]=[C:18]([CH:16]([NH:15][C:13](=[O:14])[O:12][C:8]([CH3:10])([CH3:11])[CH3:9])[CH3:17])[C:27]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)=[C:26]2[C:34]1[O:1][N:2]=[C:3]([CH3:4])[N:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 30926N-HydroxyacetamidineHCID 69673908HCID 69673908, compound

Product 1

HCID 69675865HCID 69675865, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of N′-hydroxyacetimidamide (0.081 g, 1.093 mmol) and molecular sieves 4 Å (powder, 0.3 g) in THF (3.64 mL) was added 60% sodium hydride in mineral oil (0.109 g, 2.73 mmol) at rt and the mixture was stirred at 50° C. After being stirred at 50° C. for 30 min, a solution of methyl 2-(1-(tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)quinoline-4-carboxylate (0.233 g, 0.547 mmol) in THF (1.822 mL) was added. The mixture was heated under reflux. After 3 h, the mixture was removed by filtration though a Celite™ pad and the pad was washed with DCM (2×100 mL). The organic filtrate was washed with water (100 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give tert-butyl 1-(6-fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)-3-(pyridin-2-yl)quinolin-2-yl)ethylcarbamate as a light yellow syrup: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.60 (1H, d, J=4.5 Hz), 8.28 (1H, dd, J=9.3, 5.6 Hz), 7.83-7.94 (2H, m), 7.76 (1H, dd, J=10.0, 2.7 Hz), 7.38-7.51 (2H, m), 7.18 (1H, d, J=7.2 Hz), 4.89 (1H, quin, J=6.7 Hz), 2.38 (3H, s), 1.21-1.35 (12H, m); LC-MS (ESI) m/z 450.1 [M+H]+. The light yellow syrup was carried on crude without purification for the next step.

Workup

  1. stirringAfter being stirred at 50° C. for 30 min
  2. temperatureThe mixture was heated
  3. temperatureunder reflux
  4. customthe mixture was removed by filtration though a Celite™ pad
  5. washthe pad was washed with DCM (2×100 mL)
  6. washThe organic filtrate was washed with water (100 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dff80890fac242faafb4163119585774
Source dataset
uspto-grants-2014_07
Patent number
US08765768B2

Reaction notes

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