Potassium Phosphate, Tribasic → HCID 59631571, compound

Temperature

90 °C

A stirred mixture of 5-bromo-2-chloropyridin-3-amine (0.39 g, 1.9 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.48 g, 2.3 mmol), ground 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl, (S-Phos) (0.15 g, 0.37 mmol), palladium (II) acetate (42.9 mg, 0.19 mmol), and potassium phosphate tribasic (1.20 g, 5.7 mmol) in DMF (9 mL) and water (0.4 mL) was purged 3 times with argon and placed under vacuum 3 times. The reaction mixture was carefully heated to 90° C. After 4.5 h, the reaction was cooled to rt, then diluted with water and extracted 3 times with EtOAc. The organic extractions were combined and washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. The residue was purified using silica gel chromatography (0-100% EtOAc in hexanes) to afford a light yellow solid as 2-chloro-5-(3,6-dihydro-2H-pyran-4-yl)pyridin-3-amine. 1H NMR (400 MHz, CDCl3) δ ppm 7.87 (1H, d, J=1.8 Hz), 7.05 (1H, m), 6.16 (1H, m), 4.32 (2H, q, J=2.9 Hz), 3.93 (2H, t, J=5.5 Hz), 2.51 (2H, m). 2,5-bis(3,6-dihydro-2H-pyran-4-yl)pyridin-3-amine was also isolated. 1H NMR (400 MHz, CDCl3) δ ppm 8.13 (1H, d, J=2.0 Hz), 7.11 (1H, br. s.), 6.34 (2H, m), 4.46 (4H, m), 4.20 (6H, m), 2.67 (2H, m), 2.55 (2H, m). Mass Spectrum (pos.) m/e: 259.1 (M+1).

1. customwas purged 3 times with argon
2. temperaturethe reaction was cooled to rt
3. additiondiluted with water
4. extractionextracted 3 times with EtOAc
5. extractionThe organic extractions
6. washwashed twice with brine
7. dry with materialAfter drying over anhydrous sodium sulfate and filtration
8. customthe organic solvent was removed under reduced pressure
9. customThe residue was purified

ORD record

ord-6732558827eb4ac9ae138b66d449e18e

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940724B2