Potassium sodium tartarate → (1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamine

Temperature

-78 °C

106 mg of 1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropanecarbonitrile (step 2) was dissolved in 2 ml of dichloromethane and was cooled down to −78° C. Then 0.91 ml of diisobutylaluminium hydride (1M in tetrahydrofuran) was added dropwise. The reaction mixture was stirred at −78° C. for 1 h, then at ambient temperature for three days. Then 0.40 ml of diisobutylaluminium hydride solution was added again at −78° C. and the reaction mixture was warmed to 40° C. and stirred for 24 hours. The reaction mixture was poured into a saturated solution of potassium sodium tartrate and the resulting mixture was stirred for 1 hour. The aqueous phase was extracted with three 25 ml portions dichloromethane. The organic phase was dried over sodium sulfate, filtered and concentrated. 140 mg of crude material was obtained as a yellow sticky solid. The residue was partitioned between 1N aqueous hydrochloric acid and ethyl acetate. The aqueous phase was adjusted to pH 14 by addition of an aqueous solution of sodium hydroxide and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated. Thus, 50 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine was obtained as a yellow sticky solid. 1H-NMR (CDCl3): 8.50 ppm (s, 1H), 7.83 ppm (s, 1H), 2.95 ppm (s, 2H), 1.40 ppm (s, 2H, broad), 0.99 ppm (m, 2H), 0.90 ppm (m, 2H).

1. waitat ambient temperature for three days
2. temperaturethe reaction mixture was warmed to 40° C.
3. stirringstirred for 24 hours
4. stirringthe resulting mixture was stirred for 1 hour
5. extractionThe aqueous phase was extracted with three 25 ml portions dichloromethane
6. dry with materialThe organic phase was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. custom140 mg of crude material was obtained as a yellow sticky solid
10. customThe residue was partitioned between 1N aqueous hydrochloric acid and ethyl acetate
11. additionThe aqueous phase was adjusted to pH 14 by addition of an aqueous solution of sodium hydroxide
12. extractionextracted with ethyl acetate
13. dry with materialThe organic phase was dried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated

ORD record

ord-5090ee14e0b34473be771d627986bb7d

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040708B2