반응 #563306

반응 방정식

sodium borohydride

Sodium borohydride

Diethylenetriamine

TFA

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

→

title compound

수율 91.5%

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

수율 91.5%

용매

Methanol

반응 조건

후처리

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

실험 절차

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).

출처