Ammonia → 5-(Aminomethyl)-3-pyridinecarbonitrile

Temperature

23 °C

A solution of 5-hydroxymethyl-3-pyridinecarbonitrile (4.39 g, 32.7 mmol) in diethyl ether (250 mL) at 23° C. was saturated with gaseous HCl. Solvent was then removed in vacuo and the residue was suspended in thionyl chloride (14.3 mL, 196 mmol). The mixture was then heated at reflux for 2 hours, cooled to 23° C., and diluted with benzene (150 mL). The tan precipitate was isolated by filtration, transferred to a pressure reactor, and dissolved in methanol (30 mL). The methanolic solution was saturated with gaseous ammonia, sealed in the reaction vessel, and heated with stirring at 80° C. for 2.5 hours. After cooling to 23° C., the solution was again saturated with gaseous ammonia, sealed in the vessel, and heated at 80° C. for 5 hours. The reaction mixture was then concentrated in vacuo, and the residue was diluted with aqueous 0.5M NaOH (60 mL). The aqueous layer was extracted with chloroform (3×60 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo to provide 5-aminomethyl-3-pyridinecarbonitrile (2.79 g, 21.0 mmol, 64% yield): Rf 0.19 (20% MeOH in EtOAc); 1H NMR (DMSO-D6, 200 MHz)δ8.88 (dd, J=7,2 Hz, 1H), 8.79 (m, 1H), 8.25 (d, J=7 Hz), 3.75 (s, 2H), 2.8 (br s, 2H).

1. customat 23° C.
2. customSolvent was then removed in vacuo
3. temperatureThe mixture was then heated
4. temperatureat reflux for 2 hours
5. customThe tan precipitate was isolated by filtration
6. customtransferred to a pressure reactor
7. customsealed in the reaction vessel
8. temperatureheated
9. temperatureAfter cooling to 23° C.
10. customsealed in the vessel
11. temperatureheated at 80° C. for 5 hours
12. concentrationThe reaction mixture was then concentrated in vacuo
13. additionthe residue was diluted with aqueous 0.5M NaOH (60 mL)
14. extractionThe aqueous layer was extracted with chloroform (3×60 mL)
15. dry with materialThe combined organic extracts were dried (MgSO4)
16. filtrationfiltered
17. concentrationconcentrated in vacuo

ORD record

ord-82c6a667f236419fb21e13ca1a8d9513

Source dataset

uspto-grants-1991_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05002949