Reaction #563306

Reaction equation

sodium borohydride

Sodium borohydride

Diethylenetriamine

TFA

6-ethyl-4-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile

→

title compound

Yield 91.5%

3-(Aminomethyl)-6-ethyl-4-methyl-2(1H)-pyridinone

Yield 91.5%

Solvents

Methanol

Conditions

Workup

1. 1
   workup.STIRRINGthe reaction stirred overnight again
2. 2
   workup.STIRRINGthe reaction mixture was stirred for 30 min. at room temperature
3. 3
   OtherThe solvent was evaporated
4. 4
   workup.DISSOLUTIONthe residue was dissolved in ethyl acetate (20 mL)
5. 5
   Extractionextracted with sodium bicarbonate (2×10 mL)
6. 6
   DryingThe organics were dried over sodium sulfate
7. 7
   Concentrationconcentrated
8. 8
   workup.DISSOLUTIONThe residue was dissolved in chloroform (25 mL)
9. 9
   TemperatureThe reaction was heated to 50° C. for 3 h
10. 10
    Temperaturecooled to room temperature
11. 11
    Concentrationconcentrated
12. 12
    ConcentrationThe reaction mixture was concentrated in vacuo
13. 13
    Otherthe crude product was purified by reverse phase HPLC (eluent; 0-30% gradient ACN in H2O, 0.1% TFA)

Procedure

To a stirred solution of 6-ethyl-4-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile (1.462 g, 9.01 mmol) in Methanol (50 mL), cooled to 0° C. were added di-tertbutoxycarbonyl anhydride (4.19 mL, 18.03 mmol) and nickel(II) chloride.hexahydrate (0.214 g, 0.901 mmol). Sodium borohydride (2.387 g, 63.1 mmol) was added portionwise over 30 min, then the mixture was allowed to warm to room temperature and stirred overnight. Additional sodium borohydride (2.387 g, 63.1 mmol) was added and the reaction stirred overnight again. Diethylenetriamine (0.979 mL, 9.01 mmol) was added, and the reaction mixture was stirred for 30 min. at room temperature. The solvent was evaporated, and the residue was dissolved in ethyl acetate (20 mL) and extracted with sodium bicarbonate (2×10 mL). The organics were dried over sodium sulfate, and concentrated. The residue was dissolved in chloroform (25 mL) and TFA (3.47 mL, 45.1 mmol) was added. The reaction was heated to 50° C. for 3 h, then cooled to room temperature and concentrated. The reaction mixture was concentrated in vacuo and the crude product was purified by reverse phase HPLC (eluent; 0-30% gradient ACN in H2O, 0.1% TFA) to afford the title compound (TFA salt, 1.37 g, 54.1% yield) as a white solid. LC-MS (ES) m/z=167 [M+H]+. 1H NMR (400 MHz, DMSO-d) δ ppm 1.12 (t, J=7.58 Hz, 3H), 2.20 (s, 3H), 2.44 (q, J=7.58 Hz, 2H), 3.78-3.83 (m, 2H), 6.01 (s, 1H), 7.75-7.9 (br s, 3H), 11.86 (s, 1H).

Source