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0 °C

5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)nicotinaldehyde (1.0538 g, 1.769 mmol) was suspended in THF (16 mL) and the reaction flask was cooled in an ice water bath. Then, methylmagnesium bromide (3.0 M in diethyl ether, 1.80 mL, 5.40 mmol) was added via syringe, and the reaction was stirred at 0° C. for 25 min. Then, the reaction was treated with saturated ammonium chloride (3 mL, dropwise at first as gas evolution is observed) and water (20 mL). The reaction was diluted with EtOAc and the layers were separated. The aqueous phase was extracted with EtOAc. The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (150 mL fritted filter with about 2 inches of silica gel; 100:1 DCM/MeOH (to elute non-polar impurities) to 40:1 (to elute product)) to give 1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanol (893.8 mg). 1H NMR (400 MHz, CDCl3) δ 11.86 (s, 1H), 8.83 (d, J=2.35 Hz, 1H), 8.32 (d, J=2.35 Hz, 1H), 8.01 (dd, J=12.13 Hz, 2.15 Hz, 1H), 7.96 (d, J=2.35 Hz, 1H), 7.21 (dd, J=10.76 Hz, 8.61 Hz, 4H), 6.87 (dd, J=12.13 Hz, 8.80 Hz, 4H), 4.94-4.81 (m, 5H), 4.02 (s, 3H), 3.82 (s, 3H), 3.79 (s, 3H), 2.59 (s, 3H), 1.73 (d, J=3.72 Hz, 1H), 1.53 (d, J=6.46 Hz, 3H). m/z (ESI, pos. ion) 612 (M+H)+.

1. temperaturethe reaction flask was cooled in an ice water bath
2. customthe layers were separated
3. extractionThe aqueous phase was extracted with EtOAc
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. custompurified on a silica gel
8. filtrationfilter
9. wash(150 mL fritted filter with about 2 inches of silica gel; 100:1 DCM/MeOH (to elute non-polar impurities) to 40:1 (to elute product))