Benzeneethanamine, alpha-methyl-, phosphate (1:1) → 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Temperature

100 °C

A mixture of 5-chloro-2-fluoropyridin-3-ylboronic acid (Combi Block, Inc., 2.507 g, 14.30 mmol), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (5.24 g, 13.62 mmol), Amphos (bis-4-(di-tert-butylphosphanyl)-N,N-dimethylaniline-dichloropalladium, 0.482 g, 0.681 mmol) and potassium acetate (4.10 g, 41.8 mmol) in ethanol (100 mL) and water (10 mL) was purged with argon and heated at 100° C. overnight. The reaction mixture was cooled, concentrated to remove the EtOH and partitioned between water (50 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (2×20 mL). The combined organic phases were washed with saturated aqueous sodium chloride (100 mL). The organic phase was dried over sodium sulfate, filtered and concentrated. The crude product was purified by ISCO chromatography (hexanes/EtOAc, 15 to 50%) to give 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (3.62 g, 7.54 mmol, 55.4% yield) as a colorless sticky solid. m/z (ESI, +ve ion) 481.0 (M+H)+.

1. customwas purged with argon
2. temperatureThe reaction mixture was cooled
3. concentrationconcentrated
4. customto remove the EtOH
5. custompartitioned between water (50 mL) and EtOAc (50 mL)
6. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
7. washThe combined organic phases were washed with saturated aqueous sodium chloride (100 mL)
8. dry with materialThe organic phase was dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude product was purified by ISCO chromatography (hexanes/EtOAc, 15 to 50%)

ORD record

ord-6d43f3ec8f69498295e392f80ef7e30d

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362241B2