Hydrochloric Acid → N-(1-adamantylmethyl)-2-bromo-5-chloroisonicotinamide

Temperature

-70 °C

To a stirred solution of di-isopropylamine (2.1 ml) in anhydrous tetrahydrofuran (15 ml) at is −5° C. was added, dropwise a solution of n-butyl lithium in hexane (2.5 molar, 4.8 ml) and the resulting solution was stirred for 30 minutes and was then cooled to −70° C. To the cooled solution was added a solution of 2-bromo-5-chloropyridine (2.39 g) in anhydrous tetrahydrofuran (10 ml) maintaining the internal temperature of the reaction below −65° C. The reaction was maintained at −70° C. for 15 minutes and then a solution of 1-adamantylmethyl isocyanate (1.91 g) in anhydrous tetrahydrofuran (5 ml) was dropwise added (care exotherm). The mixture was stirred for 10 minutes and was then poured into a solution of 1M aqueous hydrochloric acid solution (50 ml) and the mixture extracted into ethyl acetate (3×25 ml). The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by chromatography on silica gel eluting with ethyl acetate:iso-hexane (1:9 to 1:4 to 1:1) to afford the sub-titled compound (2.70 g) as a white solid.

1. customat is −5° C.
2. additionwas added
3. temperaturemaintaining
4. customthe internal temperature of the reaction below −65° C
5. temperatureThe reaction was maintained at −70° C. for 15 minutes
6. extractionthe mixture extracted into ethyl acetate (3×25 ml)
7. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by chromatography on silica gel eluting with ethyl acetate:iso-hexane (1:9 to 1:4 to 1:1)

ORD record

ord-6f3117d008234e25b7d1a7e4c8d1b794

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07129246B2