Reaktion #1451705

Reaktionsgleichung

NaOH

water

4,6-diamino-2-(2-hydroxy-ethoxy)-nicotinonitrile

2,5-dimethoxyphenylacetyl chloride

N-(4-amino-5-cyano-6-isopropoxypyridin-2-yl)-2-(2,5-dimethoxyphenyl)acetamide

→

white solid

Ausbeute 5.4%

N-[4-amino-5-cyano-6-(2-hydroxyethoxy)pyridin-2-yl]-2-(2,5-dimethoxyphenyl)acetamide

Ausbeute 5.4%

Lösungsmittel

THF

pyridine

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe solvents were removed under reduced pressure
2. 2
   Extraktionextracted with 1M HCl(aq.) (2×5 mL), saturated NaHCO3(aq.) (2×5 mL), and brine (1×5 mL)
3. 3
   Trocknendried over MgSO4
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated to an oil
6. 6
   workup.DISSOLUTIONThis was dissolved in 1:1 DMSO
7. 7
   Sonstigemethanol and purified by reversed phase HPLC
8. 8
   Wascheneluting with a 5-100% CH3CN gradient in 0.01M NH4OAc(aq.)
9. 9
   Sonstigeto provide a white solid
10. 10
    workup.STIRRINGThe solution was stirred at ambient temperature for 18 hours
11. 11
    Einengenthen concentrated under reduced pressure
12. 12
    Extraktionextracted with water (1×3 mL), 2M NaOH(aq.) (1×3 mL), and brine (1×3 mL)
13. 13
    Trocknendried over MgSO4
14. 14
    Filtrationfiltered
15. 15
    Einengenconcentrated under reduced pressure to a white solid
16. 16
    SonstigeThis was recrystallized from 1 mL of methanol

Vorschrift

To a solution of 39 mg (0.20 mmol) of 4,6-diamino-2-(2-hydroxy-ethoxy)-nicotinonitrile in 0.2 mL of pyridine and 1 mL of CH2Cl2 was added 75 mg (0.39 mmol) of 2,5-dimethoxyphenylacetyl chloride (Example 60B). The mixture was stirred at ambient temperature for 1 hours then 1 mL of water was added, and the solvents were removed under reduced pressure. The residue was taken up in 10 mL of ethyl acetate, then extracted with 1M HCl(aq.) (2×5 mL), saturated NaHCO3(aq.) (2×5 mL), and brine (1×5 mL), dried over MgSO4, filtered, and concentrated to an oil. This was dissolved in 1:1 DMSO:methanol and purified by reversed phase HPLC, eluting with a 5-100% CH3CN gradient in 0.01M NH4OAc(aq.) to provide a white solid. This was dissolved in 1 mL of THF, and 1 mL of 2M NaOH(aq.) was added. The solution was stirred at ambient temperature for 18 hours then concentrated under reduced pressure. The residue was taken up in 10 mL of ethyl acetate, then extracted with water (1×3 mL), 2M NaOH(aq.) (1×3 mL), and brine (1×3 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to a white solid. This was recrystallized from 1 mL of methanol to provide 4 mg (5%) of a white solid. 1H NMR (300 MHz, d6-DMSO) δ 10.10 (s, 11H), 7.13 (s, 1H), 6.90 (m, 3H), 6.79 (m, 2H), 4.81 (t, 1H, J=5.4 Hz), 4.31 (m, 2H), 3.69 (m, 8H), 3.66 (s, 2H); MS (ESI) m/e=329 (M−EtOH+H)+, 373 (M+H)+, 371 (M−H)−.

Quelle