1-Propanol → 6-Chloro-2-propoxy-nicotinamide

HRID 1483749Notes

Reaction equation

HRID 1483749 reaction equation
[CH2:1]([OH:4])[CH2:2][CH3:3].[H-].[Na+].Cl[C:8]1[N:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:9]=1[C:10]([NH2:12])=[O:11]>CN(C=O)C>[Cl:17][C:15]1[CH:14]=[CH:13][C:9]([C:10]([NH2:12])=[O:11])=[C:8]([O:4][CH2:1][CH2:2][CH3:3])[N:16]=1

Participants

5

Reactant 3

HCID 10311-PropanolHCID 24758Sodium hydrideHCID 221427782,6-Dichloropyridine-3-carboxamide

Product 1

HCID 579687006-Chloro-2-propoxy-nicotinamideYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of propan-1-ol (2.94 mL, 39.26 mmol) in DMF (15 mL) at 0° C. was added sodium hydride (95% in mineral oil, 0.94 g, 39.26 mmol) in portions and stirred for 1 h at room temperature. This mixture was slowly added to a solution of 2,6-dichloro-nicotinamide (5.0 g, 26.17 mmol) in DMF (25 mL) at 0° C. The reaction mixture was stirred at room temperature overnight. DMF was removed under reduced pressure, and the resulting mixture was diluted with EtOAc (60 mL), washed with water (2×20 mL) and brine (2×10 mL) solution, dried over anhydrous Na2SO4, filtered, and concentrated to give yellow oil. Purification was accomplished by flash chromatography on silica gel using 5-60% EtOAc/hexanes gradient elution to yield the title compound (3.8 g, 68%) as a transparent oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.46 (d, J=8.2 Hz, 1H), 7.69 (br. s., 1H), 7.06 (d, J=8.2 Hz, 1H), 5.86 (br. s., 1H), 4.48 (t, J=6.6 Hz, 2H), 1.99-1.79 (m, 2H), 1.07 (t, J=7.4 Hz, 3H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. customDMF was removed under reduced pressure
  3. additionthe resulting mixture was diluted with EtOAc (60 mL)
  4. washwashed with water (2×20 mL) and brine (2×10 mL) solution
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give yellow oil
  9. customPurification
  10. washwas accomplished by flash chromatography on silica gel using 5-60% EtOAc/hexanes gradient elution

Sources & evidence

ORD record
ord-7d946bad5f06405898fae5ae496391dc
Source dataset
uspto-grants-2016_08
Patent number
US09416146B2

Reaction notes

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