Ethanol → 5-Aminoquinoline-8-carbonitrile

Temperature

70 °C

Compound 464B (6.00 g, 30.1 mmol) was dissolved in THF (150 mL) at reflux with mechanical stirring. EtOH (150 mL) was then added followed by aqueous ammonium chloride (2.4 g/225 mL water). The mixture was heated at 70° C. and then iron powder (325 mesh, 6.75 g, 120 mmol) was added with vigorous mechanical stirring. After 1 h, the reaction was cooled to 22° C. and filtered through Celite rinsing with methylene chloride. The filtrate was then concentrated to ˜250 mL and the pH was adjusted to 10 by addition of 1N NaOH. The solution was then extracted with ethyl acetate (5×150 mL). The combined organic layers were washed once with brine (250 mL) and then dried over anhydrous magnesium sulfate. Concentration in vacuo gave 5.09 g (100%) of compound 464C as a yellow solid. HPLC: 99% at 1.143 min (retention time) (YMC S5 ODS column, 4.6×50 mm, eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 170.16 [M+H]+.

1. temperatureat reflux with mechanical stirring
2. temperaturethe reaction was cooled to 22° C.
3. filtrationfiltered through Celite
4. washrinsing with methylene chloride
5. concentrationThe filtrate was then concentrated to ˜250 mL
6. additionthe pH was adjusted to 10 by addition of 1N NaOH
7. extractionThe solution was then extracted with ethyl acetate (5×150 mL)
8. washThe combined organic layers were washed once with brine (250 mL)
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationConcentration in vacuo

ORD record

ord-cd0e9d564d2c4af0a917e68351d05a58

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06953679B2