Sodium Cyanide → 2-(Acetamido)-6-(cyanomethyl)quinoline

HRID 1503155Notes

Reaction equation

HRID 1503155 reaction equation
[C:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH2:15]Br)[CH:11]=2)[N:6]=1)(=[O:3])[CH3:2].[C-:17]#[N:18].[Na+]>CN(C=O)C>[C:1]([NH:4][C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH2:15][C:17]#[N:18])[CH:11]=2)[N:6]=1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 8929Sodium CyanideHCID 11300436N-(6-(bromomethyl)quinolin-2-yl)acetamide

Product 1

HCID 1182521902-(Acetamido)-6-(cyanomethyl)quinolineYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Compound 46 (0.254 g, 0.91 mmol) was diluted with anhydrous DMF (10 mL), and NaCN (0.230 g, 4.55 mmol) was added. The orange mixture was stirred at room temperature for 17 h. The mixture was concentrated and partitioned between EtOAc and H2O (50 mL each) and the layers were separated. The aqueous phase was extracted with EtOAc (2×50 mL) and the combined organic layers were washed with H2O (2×80 mL) and sat aq. NaCl (50 mL), and dried over anhydrous sodium sulfate and concentrated. The residue was purified by flash column chromatography (SiO2), eluting with a gradient of 15% EtOAc in CH2Cl2 to 25% EtOAc in CH2Cl2 to yield the title compound as a white solid (0.170 g, 83%): mp 154-155° C.; 1H-NMR (500 MHz; CDCl3): δ 8.48 (d, J=8.6 Hz, 1 H), 8.22 (br s, 1 H), 8.20 (d, J=9.0 Hz, 1 H), 7.85 (d, J=8.7 Hz, 1 H), 7.81 (d, J=1.0 Hz, 1 H), 7.61 (dd, J=8.7, 2.1 Hz, 1 H), 3.96 (s, 2 H), 2.30 (s, 3 H); 13C-NMR (126 MHz; CDCl3): δ 169.1 (1 C), 151.3 (1 C), 145.8 (1 C), 138.6 (1 C), 129.8 (1 C), 128.3 (1 C), 126.74 (1 C), 126.64 (1 C), 126.2 (1 C), 117.6 (1 C), 114.9 (1 C), 25.0 (1 C), 23.7 (1 C); ESIMS m/z (rel. intensity) 472 (2M+Na+, 100).

Workup

  1. additionwas added
  2. concentrationThe mixture was concentrated
  3. custompartitioned between EtOAc and H2O (50 mL each)
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted with EtOAc (2×50 mL)
  6. washthe combined organic layers were washed with H2O (2×80 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by flash column chromatography (SiO2)
  10. washeluting with a gradient of 15% EtOAc in CH2Cl2 to 25% EtOAc in CH2Cl2

Sources & evidence

ORD record
ord-290c41b5899a4e84a798ac73335acf53
Source dataset
uspto-grants-2015_12
Patent number
US09212144B2

Reaction notes

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