Acetic Acid → HCID 178514986, Verbindung

Temperatur

85 °C

To a suspension of 3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-thiopropionimidic acid methyl ester hydroiodide (880 mg, 2.34 mmol) in 2-propanol (16 mL) were added isonicotinohydrazide (337 mg, 2.46 mmol) and sodium carbonate (248 mg, 2.34 mmol). The reaction mixture was stirred at 85° C. for 1 h. Acetic acid (32 mL) was added and the reaction mixture was stirred at 130° C. for 3 h. After cooling down to ambient temperature, all volatiles were evaporated. The residue was dissolved in acetic acid (30 mL) and the reaction mixture was stirred at 130° C. for 16 h. The reaction mixture was cooled down to RT and concentrated in vacuo. The residue was poured into saturated sodium bicarbonate solution (40 mL) and extracted with ethyl acetate (2×80 mL). The combined organic phase was washed water (40 mL) and brine (40 mL), dried over MgSO4 and concentrated in vacuo. The residue was suspended in dichloromethane, filtered, washed with dichloromethane and dried in vacuo to give the product as brown solid (480 mg (purity 80%), 0.96 mmol, 41%). The filtrate was evaporated and pure product was obtained after purification by flash chromatography (using silica gel and an ethyl acetate/heptane gradient) as light brown solid (180 mg, 562 μmol, 24.0%). MS: M=321.1 (M+H)+

1. stirringthe reaction mixture was stirred at 130° C. for 3 h
2. temperatureAfter cooling down to ambient temperature
3. customall volatiles were evaporated
4. dissolutionThe residue was dissolved in acetic acid (30 mL)
5. stirringthe reaction mixture was stirred at 130° C. for 16 h
6. temperatureThe reaction mixture was cooled down to RT
7. concentrationconcentrated in vacuo
8. additionThe residue was poured into saturated sodium bicarbonate solution (40 mL)
9. extractionextracted with ethyl acetate (2×80 mL)
10. washThe combined organic phase was washed water (40 mL) and brine (40 mL)
11. dry with materialdried over MgSO4
12. concentrationconcentrated in vacuo
13. filtrationfiltered
14. washwashed with dichloromethane
15. customdried in vacuo

ORD-Eintrag

ord-a876ef65a6894e76839e08bdeca43961

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08772510B2