3-Chloropyrazine-2-carbonitrile → (3-Chloropyrazin-2-yl)methanamine hydrochloride

To a solution of 3-chloropyrazine-2-carbonitrile (160 g, 1.147 mol) in acetic acid (1.5 L) was added Raney Nickel (50% slurry in water, 70 g, 409 mmol). The resulting mixture was stirred under 4 bar hydrogen at room temperature overnight. Raney Nickel was removed by filtration over decalite and the filtrate was concentrated under reduced pressure and co-evaporated with toluene. The remaining brown solid was dissolved in ethyl acetate at 50° C. and cooled on an ice-bath. 2M hydrogen chloride solution in diethyl ether (1.14 L) was added in 30 min. The mixture was allowed to stir at room temperature over weekend. The crystals were collected by filtration, washed with diethyl ether and dried under reduced pressure at 40° C. The product brown solid obtained was dissolved in methanol at 60° C. The mixture was filtered and partially concentrated, cooled to room temperature and diethyl ether (1000 ml) was added. The mixture was allowed to stir at room temperature overnight. The solids formed were collected by filtration, washed with diethyl ether and dried under reduced pressure at 40° C. to give 153.5 g of (3-chloropyrazin-2-yl)methanamine.hydrochloride as a brown solid (74.4%, content 77%).

1. customRaney Nickel was removed by filtration over decalite
2. concentrationthe filtrate was concentrated under reduced pressure and co-evaporated with toluene
3. dissolutionThe remaining brown solid was dissolved in ethyl acetate at 50° C.
4. temperaturecooled on an ice-bath
5. addition2M hydrogen chloride solution in diethyl ether (1.14 L) was added in 30 min
6. filtrationThe crystals were collected by filtration
7. washwashed with diethyl ether
8. customdried under reduced pressure at 40° C
9. customThe product brown solid obtained
10. filtrationThe mixture was filtered
11. concentrationpartially concentrated
12. temperaturecooled to room temperature
13. additiondiethyl ether (1000 ml) was added
14. stirringto stir at room temperature overnight
15. customThe solids formed
16. filtrationwere collected by filtration
17. washwashed with diethyl ether
18. customdried under reduced pressure at 40° C.

ORD record

ord-469084f572744e379fceeaf43b2bbaa5

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290504B2