Diisopropylamine → [6-[(4-Methoxybenzyl)(methyl)amino]-2-fluoropyridin-3-yl]boronic acid

Temperature

-60 °C

In a microwave tube was placed 2,6-difluoropyridine (0.183 mL, 2.00 mmol) and (4-methoxyphenyl)-N-methylmethanamine (0.604 g, 4.00 mmol) in 2 mL of water. The mixture was heated at 150° C. for 20 min. Water was added and the mixture was extracted with ethyl acetate (3×). The combined organic layer were dried over anhydrous sodium sulfate, filtered and concentrated to give 470 mg of a crude yellow oil, which was purified by column chromatography (3/1 hexanes/ethyl acetate) to give 400 mg of N-(4-methoxybenzyl)-6-fluoro-N-methylpyridin-2-amine as a clear, colorless oil. To a solution of diisopropylamine (1.92 mL, 13.6 mmol) in 25 mL of THF at 0° C. was added butyllithium (1.6 M in hexanes, 8.93 mL, 14.3 mmol). The mixture stirred for 30 minutes and was then cooled to −60° C. and N-(4-methoxybenzyl)-6-fluoro-N-methylpyridin-2-amine (1.760 g, 7.15 mmol) was added dropwise in 10 mL of THF. The reaction stirred for 1 h at −60° C. and then triisopropyl borate (2.88 mL, 12.5 mmol) was added and the reaction allowed to warm up to RT and stirred for 1 h. Ammonium chloride (sat.) was added and the reaction was extracted with ethyl acetate (3×). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated to give 2.13 g of a crude yellow foam, which was purified by column chromatography (3/1 hexanes/ethyl acetate to 1/1 ethyl acetate/hexanes) to give 750 mg of a off-white solid. ES+=291.2 (M+H)

1. stirringThe reaction stirred for 1 h at −60° C.
2. temperatureto warm up to RT
3. stirringstirred for 1 h
4. extractionthe reaction was extracted with ethyl acetate (3×)
5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customto give 2.13 g of a crude yellow foam, which
9. customwas purified by column chromatography (3/1 hexanes/ethyl acetate to 1/1 ethyl acetate/hexanes)

ORD record

ord-6c66cdab4d4340f39490450f8d75de90

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07759337B2